Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
A database of clinical trials and their results from Australia, New Zealand, and other countries.
account_circle
Log in
to register or update your trial
search
Search for trials
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT02303821
Registration number
NCT02303821
Ethics application status
Date submitted
20/11/2014
Date registered
1/12/2014
Date last updated
4/06/2025
Titles & IDs
Public title
Study of Carfilzomib in Combination With Induction Chemotherapy in Children With Relapsed or Refractory Acute Lymphoblastic Leukemia
Query!
Scientific title
Phase 1b/2 Study of Carfilzomib in Combination With Induction Chemotherapy in Children With Relapsed or Refractory Acute Lymphoblastic Leukemia
Query!
Secondary ID [1]
0
0
2014-001633-84
Query!
Secondary ID [2]
0
0
CFZ008
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Acute Lymphoblastic Leukemia (ALL)
0
0
Query!
Condition category
Condition code
Cancer
0
0
0
0
Query!
Leukaemia - Acute leukaemia
Query!
Cancer
0
0
0
0
Query!
Leukaemia - Chronic leukaemia
Query!
Cancer
0
0
0
0
Query!
Children's - Leukaemia & Lymphoma
Query!
Cancer
0
0
0
0
Query!
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Query!
Cancer
0
0
0
0
Query!
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Experimental: Phase 1b: Dose Escalation 1 - Subjects will receive carfilzomib in combination with induction chemotherapy, comprising an R3 backbone of dexamethasone, mitoxantrone, PEG asparaginase, and vincristine.
Subjects will have a 1 week carfilzomib single agent Lead in Window prior to the Induction Cycle.
Subjects will receive a 4 week cycle of induction chemotherapy and have the option to receive a 4 week cycle of consolidation chemotherapy (Children's Oncology Group (COG) modified Berlin Frankfurt Münster (BFM) chemotherapy backbone (6 mercaptopurine, cyclophosphamide, cytarabine, PEG asparaginase, vincristine), if stable disease or better response is achieved at the end of the Induction Cycle.
Experimental: Phase 1b: Dose Escalation 2 - Subjects will receive carfilzomib in combination with induction chemotherapy, comprising a VXLD backbone of vincristine, dexamethasone, PEG asparaginase, and daunorubicin.
Subjects will receive a 4 week cycle of carfilzomib and induction chemotherapy and then have the option to receive a 4 week cycle of consolidation chemotherapy (Children's Oncology Group (COG) modified Berlin Frankfurt Münster (BFM) chemotherapy backbone (6 mercaptopurine, cyclophosphamide, cytarabine, PEG asparaginase, vincristine), if stable disease or better response is achieved at the end of the Induction Cycle.
Experimental: Phase 2: Aged = 12 months at screening - All subjects aged = 12 months at screening.
Subjects will receive the recommended phase 2 dose (RP2D) of carfilzomib determined in Phase 1b.
Subjects will receive a 4 week cycle of carfilzomib and induction chemotherapy comprising of a VXLD backbone of vincristine, dexamethasone, PEG asparaginase and daunorubicin. Subjects will then have the option to receive a 4 week cycle of carfilzomib in combination with consolidation chemotherapy Children's Oncology Group (COG) modified Berlin Frankfurt Münster (BFM) chemotherapy backbone (6 mercaptopurine, cyclophosphamide, cytarabine, PEG asparaginase, vincristine) if subjects showed no disease progression at the end of the Induction Cycle.
Experimental: Phase 2: Aged < 12 months at screening - All subjects aged \< 12 months at screening.
Subjects will receive the recommended phase 2 dose (RP2D) of carfilzomib determined in Phase 1b.
Subjects will receive a modified 5 week cycle (based on Interfant-06) of carfilzomib and induction chemotherapy comprising of a VXLD backbone of vincristine, dexamethasone, PEG asparaginase and daunorubicin. Subjects will then have the option to receive a 5 week cycle (modified based on Interfant-06) of carfilzomib in combination with consolidation chemotherapy Children's Oncology Group (COG) modified Berlin Frankfurt Münster (BFM) chemotherapy backbone (6 mercaptopurine, cyclophosphamide, cytarabine, PEG asparaginase, vincristine), if subjects showed no disease progression at the end of the Induction Cycle.
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Phase 1b: Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
Query!
Assessment method [1]
0
0
An adverse event (AE) is any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. TEAEs are AEs that occurred after the start of study treatment and up to the end of the study or 30 days of the last study treatment, whichever is earlier. Any clinically significant changes in vital signs, electrocardiograms, and clinical laboratory tests that occurred after study treatment administration were recorded as TEAEs. Treatment-related AEs (TRAEs) were TEAEs considered related to at least one study drug by the investigator, including those with unknown relationship. A serious AE (SAE) was defined as any untoward medical occurrence that resulted in death, was immediately life threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or another medically important serious event.
Query!
Timepoint [1]
0
0
From first dose up to 30 days after the last dose of study treatment; maximum duration of treatment was 8 weeks
Query!
Primary outcome [2]
0
0
Phase 1b: Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
Query!
Assessment method [2]
0
0
A DLT was defined as any of the following toxicities assessed by the investigator as possibly, probably, or definitely attributable to carfilzomib, with protocol defined exclusions: Any Grade 4 nonhematologic toxicity, = Grade 4 neutropenia or = Grade 3 thrombocytopenia.
Query!
Timepoint [2]
0
0
Up to approximately 35 days
Query!
Primary outcome [3]
0
0
Phase 2: Percentage of Participants With Complete Remission (CR) After Induction Therapy
Query!
Assessment method [3]
0
0
CR was defined as: 1. Attainment of M1 bone marrow status (less than 5% blasts in a bone marrow aspirate and at least 200 cells counted) with no evidence of circulating blasts or extramedullary disease. 2. Recovery of peripheral counts: * Absolute neutrophil count (ANC) greater than or equal to 1000/µL * Platelet count greater than or equal to 100000/µL. * Assessed between days 29 and 45 Data was adjusted as inverse probability of treatment weight (IPTW) for the average treatment effect of the treated (IPTW-ATTW).
Query!
Timepoint [3]
0
0
Up to Day 50 (28-day cycle of induction therapy + recovery window from Day 29 to Day 45 [Day 36 to Day 50 for infants])
Query!
Secondary outcome [1]
0
0
Phase 1b: Maximum Concentration (Cmax) of Carfilzomib Alone and in Combination
Query!
Assessment method [1]
0
0
The PK parameter estimates for carfilzomib were estimated from plasma concentration-time profiles using standard noncompartmental approaches over the complete sampling interval.
Query!
Timepoint [1]
0
0
Lead-in Cycle Day 1 (7-day cycle) and Induction Cycle Day 8 (28-day cycle): pre-dose, 15 minutes (m) after the start of infusion, immediately (within 2m) before the end of infusion (EOI), EOI, 10m, 30m, 1 hour (h), 2 h, and 4h post-dose
Query!
Secondary outcome [2]
0
0
Phase 1b: Area Under the Curve (AUC) From Time 0 to the Last Quantifiable Timepoint (AUClast) of Carfilzomib
Query!
Assessment method [2]
0
0
The PK parameter estimates for carfilzomib were estimated from plasma concentration-time profiles using standard noncompartmental approaches over the complete sampling interval.
Query!
Timepoint [2]
0
0
Lead-in Cycle Day 1 (7-day cycle) and Induction Cycle Day 8 (28-day cycle): pre-dose, 15m after the start of infusion, immediately (within 2m) before the EOI, EOI, 10m, 30m, 1h, 2 h, and 4h post-dose
Query!
Secondary outcome [3]
0
0
Phase 1b: AUC From Time 0 to Infinity (AUCinf) of Carfilzomib
Query!
Assessment method [3]
0
0
The PK parameter estimates for carfilzomib were estimated from plasma concentration-time profiles using standard noncompartmental approaches over the complete sampling interval.
Query!
Timepoint [3]
0
0
Lead-in Cycle Day 1 (7-day cycle) and Induction Cycle Day 8 (28-day cycle): pre-dose, 15m after the start of infusion, immediately (within 2m) before the EOI, EOI, 10m, 30m, 1h, 2 h, and 4h post-dose
Query!
Secondary outcome [4]
0
0
Phase 1b: Percentage of Participants Who Achieved a Combined CR and CR Without Platelet Recovery (CRp) at the End of Induction Cycle
Query!
Assessment method [4]
0
0
CR was defined as the attainment of M1 bone marrow status with no evidence of circulating blasts or extramedullary disease and with recovery of peripheral counts (ANC \> 750 mcl and platelet count \> 75,000 mcl). CRp was defined as the attainment of M1 bone marrow status with no evidence of circulating blasts or extramedullary disease and with recovery of ANCs (ANC \> 750 mcl), but with insufficient recovery of platelets (\< 75,000 mcl).
Query!
Timepoint [4]
0
0
Up to approximately Day 29 of Induction Cycle (28-days cycle, assessment on Day 29)
Query!
Secondary outcome [5]
0
0
Phase 1b: Percentage of Participants Achieving Minimal Residual Disease (MRD) Status of <10-³ and <10-4 Lymphoblasts at the End of Induction Cycle
Query!
Assessment method [5]
0
0
MRD was defined as the quantification of residual lymphoblast in the blood. Assessed by next generation sequencing (NGS).
Query!
Timepoint [5]
0
0
Up to approximately Day 29 of Induction Cycle (28-days cycle, assessment on Day29)
Query!
Secondary outcome [6]
0
0
Phase 2: Number of Participants Who Experienced TEAEs
Query!
Assessment method [6]
0
0
An AE is any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. TEAEs are AEs that occurred after the start of study treatment and up to the end of the study or 30 days of the last study treatment, whichever is earlier. Any clinically significant changes in vital signs, electrocardiograms, and clinical laboratory tests that occurred after study treatment administration were recorded as TEAEs. TRAEs were TEAEs considered related to at least one study drug by the investigator, including those with unknown relationship. An SAE was defined as any untoward medical occurrence that resulted in death, was immediately life threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or another medically important serious event.
Query!
Timepoint [6]
0
0
From first dose up to 30 days after the last dose of study treatment; maximum duration of treatment was 8 weeks
Query!
Secondary outcome [7]
0
0
Phase 2: Percentage of Participants With CR With Incomplete Hematologic Recovery (CRi) After Induction Therapy or Better Remission Status
Query!
Assessment method [7]
0
0
CR was defined as: a. Attainment of M1 bone marrow status with no evidence of circulating blasts or extramedullary disease. b. Recovery of peripheral counts: - ANC = 1000/µL - Platelet count = 100 000/µL. CRi was defined as: 1. Attainment of M1 bone marrow status with no evidence of circulating blasts or extramedullary disease 2. ANC and platelet counts not fulfilling criteria for CR with partial hematologic recovery (CRh), CR without platelet recovery (CRp), or CR. CRp was defined as: a. Attainment of M1 bone marrow status with no evidence of circulating blasts or extramedullary disease b. Recovery of peripheral counts: i. ANC = 1000/µL ii. Platelet count \< 100 000/µL. CRh was defined as: 1. Attainment of M1 bone marrow status with no evidence of circulating blasts or extramedullary disease 2. Recovery of peripheral counts: i. ANC = 500/µL but \< 1000/µL ii. Platelet count = 50 000/µL but \< 100 000/µL. Data was IPTW adjusted.
Query!
Timepoint [7]
0
0
Up to Day 50 (28-day cycle of induction therapy + recovery window from Day 29 to Day 45 [up to Day 50 for infants])
Query!
Secondary outcome [8]
0
0
Phase 2: Event Free Survival (EFS)
Query!
Assessment method [8]
0
0
EFS was defined as time from initiation of therapy until treatment failure (defined as failure to reach at least a CRi after consolidation or after induction in participants that did not receive consolidation), relapse, or death from any cause. CRi was defined as: a. Attainment of M1 bone marrow status with no evidence of circulating blasts or extramedullary disease b. ANC and platelet counts not fulfilling criteria for CRh, CRp, or CR. Data was IPTW adjusted. Medians were estimated using the Kaplan-Meier (KM) method.
Query!
Timepoint [8]
0
0
Up to approximately 2 years
Query!
Secondary outcome [9]
0
0
Phase 2: Overall Survival (OS)
Query!
Assessment method [9]
0
0
OS was defined as time from initiation of therapy until death from any cause. Data was IPTW adjusted. Medians were estimated using the KM method.
Query!
Timepoint [9]
0
0
Up to approximately 2 years
Query!
Secondary outcome [10]
0
0
Phase 2: Duration of Remission (DOR)
Query!
Assessment method [10]
0
0
DOR was defined as time from earliest of CR, CRp, CRh, or CRi to relapse or death from any cause. CR was defined as: a. Attainment of M1 bone marrow status with no evidence of circulating blasts or extramedullary disease. b. Recovery of peripheral counts: - ANC = 1000/µL - Platelet count = 100 000/µL. CRi was defined as: a. Attainment of M1 bone marrow status with no evidence of circulating blasts or extramedullary disease b. ANC and platelet counts not fulfilling criteria for CRh, CRp) or CR. CRp was defined as: a. Attainment of M1 bone marrow status with no evidence of circulating blasts or extramedullary disease b. Recovery of peripheral counts: i. ANC = 1000/µL ii. Platelet count \< 100 000/µL. CRh was defined as: a. Attainment of M1 bone marrow status with no evidence of circulating blasts or extramedullary disease b. Recovery of peripheral counts: i. ANC = 500/µL but \< 1000/µL ii. Platelet count = 50 000/µL but \< 100 000/µL.
Query!
Timepoint [10]
0
0
Up to approximately 2 years
Query!
Secondary outcome [11]
0
0
Phase 2: Percentage of Participants Achieving MRD Status of <10-³ and <10-4 Cells in Participants With CR After Induction Therapy
Query!
Assessment method [11]
0
0
MRD was defined as the number of leukemia cells that remained in a participant's body after treatment. MRD was measured with next generation sequencing (NGS).
Query!
Timepoint [11]
0
0
Up to Day 50 (28-day cycle of induction therapy + recovery window from Day 29 to Day 45 [up to Day 50 for infants])
Query!
Secondary outcome [12]
0
0
Phase 2: Percentage of Participants Achieving MRD Status of <10-³ and <10-4 Cells in Participants With CRi or Better Status After Induction Therapy
Query!
Assessment method [12]
0
0
MRD was defined as the number of leukemia cells that remained in a participant's body after treatment. MRD was measured with NGS.
Query!
Timepoint [12]
0
0
Up to Day 50 (28-day cycle of induction therapy + recovery window from Day 29 to Day 45 [up to Day 50 for infants])
Query!
Secondary outcome [13]
0
0
Phase 2: Percentage of Participants Achieving MRD Status of <10-³ and <10-4 Cells in Participants With CRi or Better Status After Consolidation Therapy
Query!
Assessment method [13]
0
0
MRD was defined as the number of leukemia cells that remained in a participant's body after treatment. MRD was measured with NGS.
Query!
Timepoint [13]
0
0
Up to Day 100 (28-day cycle of induction therapy + recovery window from Day 29 to Day 45 [up to Day 50 for infants] + 28-day cycle of consolidation therapy + + recovery window from Day 29 to Day 45 [up to Day 50 for infants])
Query!
Secondary outcome [14]
0
0
Phase 2: Percentage of Participants Who Underwent Stem Cell Transplant or Chimeric Antigen Receptor T-cell (CAR-T) Without Intervening Relapse Following Protocol-Specified Therapy
Query!
Assessment method [14]
0
0
Percentage of participants who successfully underwent stem cell transplant or CAR-T therapy without experiencing a relapse after receiving the protocol-specified treatment.
Query!
Timepoint [14]
0
0
Up to approximately 2 years
Query!
Secondary outcome [15]
0
0
Phase 2: Percentage of Participants With CRi or Better Remission Status After Consolidation Therapy
Query!
Assessment method [15]
0
0
CR was defined as: a. Attainment of M1 bone marrow status with no evidence of circulating blasts or extramedullary disease. b. Recovery of peripheral counts: - ANC = 1000/µL - Platelet count = 100 000/µL. CRi was defined as: 1. Attainment of M1 bone marrow status with no evidence of circulating blasts or extramedullary disease 2. ANC and platelet counts not fulfilling criteria for CRh, CRp, or CR. CRp was defined as: a. Attainment of M1 bone marrow status with no evidence of circulating blasts or extramedullary disease b. Recovery of peripheral counts: i. ANC = to 1000/µL ii. Platelet count \< 100 000/µL. CRh was defined as: 1. Attainment of M1 bone marrow status with no evidence of circulating blasts or extramedullary disease 2. Recovery of peripheral counts: i. ANC = 500/µL but \< 1000/µL ii. Platelet count = 50 000/µL but \< 100 000/µL. Data was IPTW adjusted.
Query!
Timepoint [15]
0
0
Up to Day 100 (28-day cycle of induction therapy + recovery window from Day 29 to Day 45 [up to Day 50 for infants] + 28-day cycle of consolidation therapy + + recovery window from Day 29 to Day 45 [up to Day 50 for infants])
Query!
Secondary outcome [16]
0
0
Phase 2: AUClast of Carfilzomib
Query!
Assessment method [16]
0
0
AUClast refers to the total exposure of a drug in the body over time, calculated from the time of administration until the last measurable concentration in the blood.
Query!
Timepoint [16]
0
0
Day 8 of induction cycle (28-days cycle) and Day 1 of consolidation cycle (28-days cycle)
Query!
Secondary outcome [17]
0
0
Phase 2: AUCinf of Carfilzomib
Query!
Assessment method [17]
0
0
AUCinf represents the total drug exposure over time, extrapolated from the time of administration until the drug is completely eliminated from the body.
Query!
Timepoint [17]
0
0
Day 8 of induction cycle (28-days cycle) and Day 1 of consolidation cycle (28-days cycle)
Query!
Secondary outcome [18]
0
0
Phase 2: Cmax of Carfilzomib
Query!
Assessment method [18]
0
0
Cmax is the maximum concentration of a drug in the bloodstream after administration.
Query!
Timepoint [18]
0
0
Day 8 of induction cycle (28-days cycle) and Day 1 of consolidation cycle (28-days cycle)
Query!
Secondary outcome [19]
0
0
Phase 2: Terminal Half-life (t1/2,z) of Carfilzomib
Query!
Assessment method [19]
0
0
T1/2,z refers to the time required for the plasma concentration of a drug to decrease by half during the final phase of elimination from the body.
Query!
Timepoint [19]
0
0
Day 8 of induction cycle (28-days cycle) and Day 1 of consolidation cycle (28-days cycle)
Query!
Eligibility
Key inclusion criteria
Phase 1b Key
1. Age 21 years or younger at the time of initial ALL diagnosis and age > 1 year at the time of study treatment initiation.
2. Subjects must have a diagnosis of relapsed or refractory ALL with = 5% blasts in the bone marrow (M2 or M3 disease), with or without extramedullary disease.
-To be eligible, subjects must have had 1 or more prior therapeutic attempts, defined as:
* Early first relapse (< 36 months from original diagnosis) after achieving a CR (B-ALL) or first relapse any time following the original diagnosis after achieving a CR (T-ALL)
* First refractory bone marrow relapse occurring any time after original diagnosis after achieving a CR (ie, =1 failed attempt to induce a second remission) OR
* Relapse after achieving a CR following the first or subsequent relapse (i.e., = 2 relapses) OR
* Failing to achieve a CR from original diagnosis after at least 1 induction attempt
3. Subjects must have fully recovered from the acute toxic effects of all previous chemotherapy, immunotherapy, or radiotherapy treatment before enrollment.
4. Subjects must have a serum creatinine level that is = 1.5 × institutional upper limit of normal (ULN) according to age. If serum creatinine level is > 1.5 × ULN, the subject must have a calculated creatinine clearance or radioisotope glomerular filtration rate (GFR) = 70 mL/min/1.73 m2.
5. Adequate liver function, defined as both of the following:
* Total bilirubin = 1.5 × institutional ULN except in the presence of Gilbert Syndrome
* Alanine aminotransferase (ALT) = 5 × institutional ULN
6. Performance status: Karnofsky or Lansky scores = 50 for subjects > 16 years old or = 16 years old, respectively.
Phase 2
1. Subject's legally acceptable representative has provided informed consent when the subject is legally too young to provide informed consent and the subject has provided written assent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated, except for standard of care local testing as permitted per protocol.
2. Age greater than or equal to 1 month to less than 21 years. Subjects greater than or equal to 18 years must have had their original diagnosis at less than 18 years of age.
3. Subjects must be diagnosed with relapsed or refractory relapsed ALL.
4. Subjects must have a documented first remission, less than 5% blasts in the bone marrow (M1 bone marrow) and no evidence of extramedullary disease.
5. T-cell ALL with bone marrow relapse (defined as greater than or equal to 5% leukemia blasts in bone marrow) or refractory relapse with or without extramedullary disease.
OR B-cell ALL bone marrow relapse or refractory relapse (defined as greater than or equal to 5% leukemia blasts in bone marrow) after having received a targeted B-cell immune therapy (eg, blinatumomab, inotuzumab or a CAR-T therapy) with or without extramedullary disease..
6. Adequate liver function: bilirubin less than or equal to 1.5 x upper limit of normal (ULN), alanine aminotransferase (ALT) less than or equal to 5 x ULN.
7. Adequate renal function: serum creatinine less than or equal to 1.5 x ULN or glomerular filtration rate (GFR) greater than or equal to 70 mL/min/1.73 m^2; or for children less than 2 years of age, greater than or equal to 50 mL/min/1.73 m^2.
8. Adequate cardiac function: shortening fraction greater than or equal to 30% or ejection fraction greater than or equal to 50%.
9. Karnofsky (subjects greater than or equal to 16 years of age) or Lansky (subjects 12 months to less than 16 years of age) performance status greater than or equal to 50%.
10. Subjects must have fully recovered from the acute toxic effects of all previous chemotherapy, immunotherapy, or radiotherapy treatment before enrollment (for example: recovery from gastrointestinal toxicity may occur more rapidly than less reversible organ toxicities such as sinusoidal obstruction syndrome or non-infectious pneumonitis, for serious prior toxicities recommended discussion with Amgen medical monitor).
11. Life expectancy of greater than 6 weeks per investigator's judgement at time of screening.
Phase 1b Key
Query!
Minimum age
1
Month
Query!
Query!
Maximum age
21
Years
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
1. Known allergy to any of the drugs used in the study (Subjects who have had a previous allergy to PEG-asparaginase and if able, may receive Erwinia asparaginase at the investigator's discretion)
2. Known allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
3. Left ventricular fractional shortening < 30%
4. History of = Grade 2 pancreatitis
5. Active graft-versus-host disease requiring systemic treatment
6. Positive culture for or other clinical evidence of infection with bacteria or fungus within 14 days of the initiation of study treatment
7. Down Syndrome
8. Prior therapy restrictions:
* Subjects must have completed therapy with granulocyte-colony stimulating factor (G-CSF) or other myeloid growth factors at least 7 days before study treatment initiation, or at least 14 days before study treatment initiation, if pegylated myeloid growth factors were administered.
* Subjects must have completed any type of active immunotherapy (e.g., tumor vaccines) at least 42 days before study treatment initiation.
* Subjects must have received the last dose of a non-monoclonal antibody biologic agent at least 7 days before study treatment initiation.
* At least 3 antibody half-lives must have elapsed since the last dose of monoclonal antibody (e.g., 66 days for rituximab and 69 days for epratuzumab) before subjects may initiate study treatment.
* Subjects must not have received other antineoplastic agents with therapeutic intent, excluding hydroxyurea and antimetabolites administered as part of maintenance chemotherapy, within 7 days prior to study treatment initiation.
9. Hepatitis B infection with positive hepatitis B DNA
Phase 2
1. Prior treatment with carfilzomib.
2. Intolerance, hypersensitivity, or inability to receive any of the chemotherapy components of the VXLD regimen. An exception is allowed for allergy to asparaginase products if Erwinia asparaginase is unable to be administered,
3. Autologous HSCT within 6 weeks prior to start of study treatment.
4. Allogeneic HSCT within 3 months prior to start of study treatment.
5. Active GVHD requiring systemic immune suppression.
6. Less than 30 days from discontinuation of immune suppressive therapy administered for the treatment of acute or chronic GVHD.
7. Isolated extramedullary relapse.
8. Positive bacterial or fungal infection within 14 days of enrollment (except for documented line infection, line has been removed, and blood culture after line removal is negative for 5 days prior to first dose of induction therapy). Antibiotics may be administered for prophylaxis as per institutional standards up to and after enrollment.
9. Subjects with less than 3 antibody half-lives since the last dose of monoclonal antibody (eg, 66 days for rituximab, 69 days for epratuzumab, inotuzumab for 36 days), prior to first dose of investigational product must be discussed with the Amgen medical monitor and may be allowed to enroll based on extent of disease or evidence of rapidly rising peripheral or bone marrow blast counts.
10. Cell-based immunotherapy (eg, donor leucocyte infusion, CAR-T cells, tumor vaccines) within 42 days prior to first dose of investigational product. If the Amgen medical monitor agrees, an exception may be granted to the 42-day requirement for subjects with rapidly rising peripheral or bone marrow blast counts.
11. Down's syndrome.
12. Presence of another active cancer.
13. History of grade greater than or equal to 2 pancreatitis within 6 months to screening.
14. Unresolved toxicities from prior anticancer therapy, defined as not having resolved to CTCAE version 4.03 grade 1 or to levels dictated in the eligibility criteria apart from alopecia or toxicities from prior anticancer therapy that are considered irreversible and do not trigger another exclusion criterion (defined as having been present and stable for greater than 4 weeks).
15. Antitumor therapy (chemotherapy, investigational agents, molecular-targeted therapy) within 7 days of day 1 of induction. Exception: hydroxyurea to control peripheral blood leukemic cell counts is allowed until start of investigational product.
16. Active viral infection, including but not limited to cytomegalovirus (CMV), Hepatitis B infection with positive serum hepatitis surface antigen or hepatitis B DNA, HIV, Hepatitis C with detectable hepatitis C RNA. Subjects who have previously received a stem cell transplant must be screened for CMV infection, unless both subject and donor are known to be CMV negative.
17. Currently receiving treatment in another investigational device or product study, or less than 14 days since ending treatment on another investigational device or product study.
18. Uncontrolled arrhythmias or screening ECG with corrected QT interval (QTc) of greater than 470 msec.
19. History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
20. Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 6 months after the last dose of any study treatment or for 12 months after last dose of cyclophosphamide if administered during optional consolidation cycle.
21. Female subjects of childbearing potential unwilling to use 1 highly effective method of contraception during treatment and for an additional 6 months after the last dose of any study treatment or for 12 months after last dose of cyclophosphamide if administered during optional consolidation cycle.
22. Female subjects of childbearing potential with a positive pregnancy test assessed at Screening by a serum or urine pregnancy test.
23. Male subjects with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use a condom with spermicide during treatment and for an additional 6 months after the last dose of any study treatment, even if they have undergone a successful vasectomy.
24. Male subjects with a pregnant partner who are unwilling to practice abstinence or use a condom with spermicide during treatment, for duration of pregnancy, and for an additional 6 months after the last dose of any study treatment.
25. Male subjects unwilling to abstain from donating semen or sperm during treatment and for an additional 6 months after the last dose of any study treatment.
26. Known allergy to captisol (a cyclodextrin derivative used to solubilize carfilzomib; for a complete listing of Captisol-enabled drugs, see the Ligand Pharmaceuticals, Inc. website).
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Non-randomised trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Single group
Query!
Other design features
Query!
Phase
Phase 1
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
16/02/2015
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
28/06/2024
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
141
Query!
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Query!
Recruitment hospital [1]
0
0
Sydney Childrens Hospital - Randwick
Query!
Recruitment hospital [2]
0
0
The Childrens Hospital at Westmead - Westmead
Query!
Recruitment hospital [3]
0
0
Queensland Childrens Hospital - South Brisbane
Query!
Recruitment hospital [4]
0
0
The Royal Childrens Hospital - Parkville
Query!
Recruitment hospital [5]
0
0
Perth Childrens Hospital - Nedlands
Query!
Recruitment postcode(s) [1]
0
0
2031 - Randwick
Query!
Recruitment postcode(s) [2]
0
0
2145 - Westmead
Query!
Recruitment postcode(s) [3]
0
0
4101 - South Brisbane
Query!
Recruitment postcode(s) [4]
0
0
3052 - Parkville
Query!
Recruitment postcode(s) [5]
0
0
6909 - Nedlands
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
California
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Colorado
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Georgia
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Illinois
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
Maryland
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
Minnesota
Query!
Country [7]
0
0
United States of America
Query!
State/province [7]
0
0
Missouri
Query!
Country [8]
0
0
United States of America
Query!
State/province [8]
0
0
New Jersey
Query!
Country [9]
0
0
United States of America
Query!
State/province [9]
0
0
New York
Query!
Country [10]
0
0
United States of America
Query!
State/province [10]
0
0
North Carolina
Query!
Country [11]
0
0
United States of America
Query!
State/province [11]
0
0
Ohio
Query!
Country [12]
0
0
United States of America
Query!
State/province [12]
0
0
Pennsylvania
Query!
Country [13]
0
0
United States of America
Query!
State/province [13]
0
0
Tennessee
Query!
Country [14]
0
0
United States of America
Query!
State/province [14]
0
0
Texas
Query!
Country [15]
0
0
United States of America
Query!
State/province [15]
0
0
Utah
Query!
Country [16]
0
0
United States of America
Query!
State/province [16]
0
0
West Virginia
Query!
Country [17]
0
0
United States of America
Query!
State/province [17]
0
0
Wisconsin
Query!
Country [18]
0
0
Argentina
Query!
State/province [18]
0
0
Buenos Aires
Query!
Country [19]
0
0
Austria
Query!
State/province [19]
0
0
Wien
Query!
Country [20]
0
0
Brazil
Query!
State/province [20]
0
0
Bahia
Query!
Country [21]
0
0
Brazil
Query!
State/province [21]
0
0
Distrito Federal
Query!
Country [22]
0
0
Brazil
Query!
State/province [22]
0
0
Paraná
Query!
Country [23]
0
0
Brazil
Query!
State/province [23]
0
0
Pernambuco
Query!
Country [24]
0
0
Brazil
Query!
State/province [24]
0
0
Rio Grande Do Sul
Query!
Country [25]
0
0
Brazil
Query!
State/province [25]
0
0
São Paulo
Query!
Country [26]
0
0
Bulgaria
Query!
State/province [26]
0
0
Sofia
Query!
Country [27]
0
0
Canada
Query!
State/province [27]
0
0
Quebec
Query!
Country [28]
0
0
Chile
Query!
State/province [28]
0
0
Santiago de Chile
Query!
Country [29]
0
0
Chile
Query!
State/province [29]
0
0
Santiago
Query!
Country [30]
0
0
Colombia
Query!
State/province [30]
0
0
Cesar
Query!
Country [31]
0
0
Colombia
Query!
State/province [31]
0
0
Valle Del Cauca
Query!
Country [32]
0
0
Czechia
Query!
State/province [32]
0
0
Brno
Query!
Country [33]
0
0
Denmark
Query!
State/province [33]
0
0
Kobenhavn O
Query!
Country [34]
0
0
France
Query!
State/province [34]
0
0
Bordeaux Cedex
Query!
Country [35]
0
0
France
Query!
State/province [35]
0
0
Lille
Query!
Country [36]
0
0
France
Query!
State/province [36]
0
0
Paris
Query!
Country [37]
0
0
France
Query!
State/province [37]
0
0
Toulouse Cedex 9
Query!
Country [38]
0
0
France
Query!
State/province [38]
0
0
Vandoeuvre les Nancy Cedex
Query!
Country [39]
0
0
Greece
Query!
State/province [39]
0
0
Athens
Query!
Country [40]
0
0
Greece
Query!
State/province [40]
0
0
Goudi
Query!
Country [41]
0
0
Greece
Query!
State/province [41]
0
0
Patra
Query!
Country [42]
0
0
Greece
Query!
State/province [42]
0
0
Thessaloniki
Query!
Country [43]
0
0
Hong Kong
Query!
State/province [43]
0
0
Kowloon Bay
Query!
Country [44]
0
0
Israel
Query!
State/province [44]
0
0
Tel Hashomer
Query!
Country [45]
0
0
Italy
Query!
State/province [45]
0
0
Bari
Query!
Country [46]
0
0
Italy
Query!
State/province [46]
0
0
Catania
Query!
Country [47]
0
0
Italy
Query!
State/province [47]
0
0
Genova
Query!
Country [48]
0
0
Italy
Query!
State/province [48]
0
0
Monza (MB)
Query!
Country [49]
0
0
Italy
Query!
State/province [49]
0
0
Napoli
Query!
Country [50]
0
0
Italy
Query!
State/province [50]
0
0
Padova
Query!
Country [51]
0
0
Italy
Query!
State/province [51]
0
0
Pavia
Query!
Country [52]
0
0
Italy
Query!
State/province [52]
0
0
Roma
Query!
Country [53]
0
0
Italy
Query!
State/province [53]
0
0
Torino
Query!
Country [54]
0
0
Korea, Republic of
Query!
State/province [54]
0
0
Seoul
Query!
Country [55]
0
0
Korea, Republic of
Query!
State/province [55]
0
0
Yangsan-si, Gyeongsangnam-do
Query!
Country [56]
0
0
Mexico
Query!
State/province [56]
0
0
Distrito Federal
Query!
Country [57]
0
0
Mexico
Query!
State/province [57]
0
0
Jalisco
Query!
Country [58]
0
0
Mexico
Query!
State/province [58]
0
0
Puebla
Query!
Country [59]
0
0
Netherlands
Query!
State/province [59]
0
0
Utrecht
Query!
Country [60]
0
0
Norway
Query!
State/province [60]
0
0
Oslo
Query!
Country [61]
0
0
Poland
Query!
State/province [61]
0
0
Krakow
Query!
Country [62]
0
0
Poland
Query!
State/province [62]
0
0
Lodz
Query!
Country [63]
0
0
Poland
Query!
State/province [63]
0
0
Lublin
Query!
Country [64]
0
0
Poland
Query!
State/province [64]
0
0
Warszawa
Query!
Country [65]
0
0
Poland
Query!
State/province [65]
0
0
Wroclaw
Query!
Country [66]
0
0
Poland
Query!
State/province [66]
0
0
Zabrze
Query!
Country [67]
0
0
Portugal
Query!
State/province [67]
0
0
Coimbra
Query!
Country [68]
0
0
Portugal
Query!
State/province [68]
0
0
Lisboa
Query!
Country [69]
0
0
Portugal
Query!
State/province [69]
0
0
Porto
Query!
Country [70]
0
0
Romania
Query!
State/province [70]
0
0
Bucharest
Query!
Country [71]
0
0
Romania
Query!
State/province [71]
0
0
Cluj Napoca
Query!
Country [72]
0
0
Romania
Query!
State/province [72]
0
0
Timisoara
Query!
Country [73]
0
0
Russian Federation
Query!
State/province [73]
0
0
Moscow
Query!
Country [74]
0
0
Russian Federation
Query!
State/province [74]
0
0
Saint Petersburg
Query!
Country [75]
0
0
Saudi Arabia
Query!
State/province [75]
0
0
Riyadh
Query!
Country [76]
0
0
Singapore
Query!
State/province [76]
0
0
Singapore
Query!
Country [77]
0
0
South Africa
Query!
State/province [77]
0
0
Johannesburg
Query!
Country [78]
0
0
Spain
Query!
State/province [78]
0
0
Cataluña
Query!
Country [79]
0
0
Spain
Query!
State/province [79]
0
0
Madrid
Query!
Country [80]
0
0
Sweden
Query!
State/province [80]
0
0
Solna
Query!
Country [81]
0
0
Taiwan
Query!
State/province [81]
0
0
Taipei
Query!
Country [82]
0
0
Taiwan
Query!
State/province [82]
0
0
Taoyuan
Query!
Country [83]
0
0
Thailand
Query!
State/province [83]
0
0
Bangkok
Query!
Country [84]
0
0
Turkey
Query!
State/province [84]
0
0
Adana
Query!
Country [85]
0
0
Turkey
Query!
State/province [85]
0
0
Ankara
Query!
Country [86]
0
0
Turkey
Query!
State/province [86]
0
0
Antalya
Query!
Country [87]
0
0
Turkey
Query!
State/province [87]
0
0
Bursa
Query!
Country [88]
0
0
Turkey
Query!
State/province [88]
0
0
Istanbul
Query!
Country [89]
0
0
Turkey
Query!
State/province [89]
0
0
Izmir
Query!
Country [90]
0
0
Turkey
Query!
State/province [90]
0
0
Kayseri
Query!
Country [91]
0
0
United Kingdom
Query!
State/province [91]
0
0
Sutton
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Query!
Name
Amgen
Query!
Address
Query!
Country
Query!
Other collaborator category [1]
0
0
Other
Query!
Name [1]
0
0
Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) - Study Design & Execution Collaborator
Query!
Address [1]
0
0
Query!
Country [1]
0
0
Query!
Other collaborator category [2]
0
0
Other
Query!
Name [2]
0
0
Innovative Therapies For Children with Cancer Consortium
Query!
Address [2]
0
0
Query!
Country [2]
0
0
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
The purpose of Phase 1b of this study is to: * Asses the safety, tolerability and activity of carfilzomib, alone and in combination with induction chemotherapy, in children with relapsed or refractory acute lymphoblastic leukemia (ALL). * Determine the maximum tolerated dose (MTD) and to recommend a phase 2 dose of carfilzomib in combination with induction chemotherapy. The purpose of Phase 2 of this study is to compare the rate of complete remission (CR) of carfilzomib in combination with vincristine, dexamethasone, PEG asparaginase, daunorubicin (VXLD) at the end of induction therapy to an appropriate external control.
Query!
Trial website
https://clinicaltrials.gov/study/NCT02303821
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
MD
Query!
Address
0
0
Amgen
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Study protocol
https://cdn.clinicaltrials.gov/large-docs/21/NCT02303821/Prot_000.pdf
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/21/NCT02303821/SAP_001.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT02303821
Download to PDF