We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

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
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02303821




Registration number
NCT02303821
Ethics application status
Date submitted
20/11/2014
Date registered
1/12/2014
Date last updated
10/05/2021

Titles & IDs
Public title
Study of Carfilzomib in Combination With Induction Chemotherapy in Children With Relapsed or Refractory Acute Lymphoblastic Leukemia
Scientific title
Phase 1b/2 Study of Carfilzomib in Combination With Induction Chemotherapy in Children With Relapsed or Refractory Acute Lymphoblastic Leukemia
Secondary ID [1] 0 0
2014-001633-84
Secondary ID [2] 0 0
CFZ008
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Lymphoblastic Leukemia (ALL) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Carfilzomib
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Mitoxantrone
Treatment: Drugs - PEG-asparaginase
Treatment: Drugs - Vincristine
Treatment: Drugs - Intrathecal (IT) Methotrexate
Treatment: Drugs - Intrathecal Triple Therapy (Intrathecal Cytarabine, Hydrocortisone, and Methotrexate)
Treatment: Drugs - 6-Mercaptopurine
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Cytarabine
Treatment: Drugs - Daunorubicin

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.


Treatment: Drugs: Carfilzomib


Treatment: Drugs: Dexamethasone


Treatment: Drugs: Mitoxantrone


Treatment: Drugs: PEG-asparaginase


Treatment: Drugs: Vincristine


Treatment: Drugs: Intrathecal (IT) Methotrexate


Treatment: Drugs: Intrathecal Triple Therapy (Intrathecal Cytarabine, Hydrocortisone, and Methotrexate)


Treatment: Drugs: 6-Mercaptopurine


Treatment: Drugs: Cyclophosphamide


Treatment: Drugs: Cytarabine


Treatment: Drugs: Daunorubicin


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1b: Number of Subjects who Experience One or More Adverse Events (AE)
Timepoint [1] 0 0
36 months
Primary outcome [2] 0 0
Phase 1b: Number of Subjects who Experience One or More Serious Adverse Events (SAEs)
Timepoint [2] 0 0
36 months
Primary outcome [3] 0 0
Phase 1b: Number of Subjects who Experienced a Clinically Significant Change from Baseline in Key Laboratory Analytes - Changes from baseline in key laboratory analytes.
Timepoint [3] 0 0
36 months
Primary outcome [4] 0 0
Phase 1b: Number of Subjects who Experience a Clinically Significant Change from Baseline in Vital Signs - Changes from baseline in vital signs
Timepoint [4] 0 0
36 months
Primary outcome [5] 0 0
Phase 1b: Number of Subjects who Experience a Clinically Significant Change from Baseline in Physical Findings - Changes from baseline in physical findings
Timepoint [5] 0 0
36 months
Primary outcome [6] 0 0
Phase 1b: Time to Toxicity - Time to toxicity will be evaluated to differentiate single-agent carfilzomib from carfilzomib in combination with induction chemotherapy
Timepoint [6] 0 0
36 months
Primary outcome [7] 0 0
Phase 1b: Maximum Tolerated Dose (MTD) - Maximum tolerated dose (MTD) of carfilzomib in combination with induction chemotherapy. Determination of the MTD as the dose that has the highest posterior probability of having a dose-limiting toxicity (DLT) rate within the target toxicity interval (20%-33%), while the posterior probability of excessive/unacceptable toxicity (>33%-100%) is less than 40%.
Timepoint [7] 0 0
36 months
Primary outcome [8] 0 0
Phase 2: Complete Response (CR) Rate After Induction Therapy in Subjects Aged = 12 Months at Screening - CR will be assessed in all subjects who do not show disease progression during induction therapy (Day 1 to Day 28) between Day 29 and Day 45, or start of alternative therapy, whichever comes first. Subjects can receive alternative therapy after completing induction therapy on Day 28.
Timepoint [8] 0 0
From Day 29 up to a maximum of Day 45
Primary outcome [9] 0 0
Phase 2: Complete Response (CR) Rate After Induction Therapy in Subjects Aged < 12 Months at Screening - CR will be assessed in all subjects who do not show disease progression during induction therapy (Modified based on Interfant-06: Day 1 to Day 35) between Day 36 and Day 50, or start of alternative therapy, whichever comes first. Subjects can receive alternative therapy after completing induction therapy on Day 35.
Timepoint [9] 0 0
From Day 36 up to a maximum of Day 50
Secondary outcome [1] 0 0
Phase 1b: Maximum plasma concentration (Cmax) - Maximum plasma concentration (Cmax), alone and in combination with induction chemotherapy, will be derived from levels of carfilzomib assayed in Pharmacokinetic (PK) samples. Estimates for Cmax will be tabulated and summarized (i.e., mean, standard deviation).
Timepoint [1] 0 0
36 months
Secondary outcome [2] 0 0
Phase 1b: Total Plasma Exposure - Area Under the Curve (AUC) - Total Plasma Exposure - Area Under the Curve (AUC), alone and in combination with induction chemotherapy, will be derived from levels of carfilzomib assayed in Pharmacokinetic (PK) samples. Estimates for AUC will be tabulated and summarized (i.e., mean, standard deviation).
Timepoint [2] 0 0
36 months
Secondary outcome [3] 0 0
Phase 1b: Number of Subjects who Experience Complete Response (CR) or Complete Response with Incomplete Hematological Recovery (CRi)
Timepoint [3] 0 0
36 months
Secondary outcome [4] 0 0
Phase 1b: Minimal Residual Disease (MRD) Status - Proportion of subjects who achieve MRD status < 10-3 and < 10-4 lymphoblasts at the end of the Induction Cycle as assessed by quantitative immunoglobulin/T-cell receptor (Ig/TcR) polymerase chain reaction (PCR)
Timepoint [4] 0 0
36 months
Secondary outcome [5] 0 0
Phase 2: Number of Subjects who Experience a Treatment-emergent Adverse Event (TEAE)
Timepoint [5] 0 0
29 months
Secondary outcome [6] 0 0
Phase 2: Number of Subjects who Experience a Treatment-related Adverse Event
Timepoint [6] 0 0
29 months
Secondary outcome [7] 0 0
Phase 2: Number of Subjects who Experience a Severe Adverse Event
Timepoint [7] 0 0
29 months
Secondary outcome [8] 0 0
Phase 2: Number of Subjects who Experience a Laboratory Abnormality
Timepoint [8] 0 0
29 months
Secondary outcome [9] 0 0
Phase 2: Number of Subjects who Experience Complete Response (CR), Complete Response with Incomplete Recovery of Platelets (CRp), or Complete Response with Incomplete Hematological Recovery (CRi)
Timepoint [9] 0 0
29 months
Secondary outcome [10] 0 0
Phase 2: Event Free Survival (EFS) - EFS, 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 subjects that do not receive consolidation), relapse, or death from any cause.
Timepoint [10] 0 0
29 months
Secondary outcome [11] 0 0
Phase 2: Overall Survival (OS) - OS defined as time from initiation of therapy until death from any cause.
Timepoint [11] 0 0
29 months
Secondary outcome [12] 0 0
Phase 2: Duration of Response (DOR) - DOR, defined as time from earliest of CR, CRp, CRh, or CRi to relapse or death from any cause.
Timepoint [12] 0 0
29 months
Secondary outcome [13] 0 0
Phase 2: Minimal Residual Disease (MRD) Status in all Subjects - Proportion of subjects who achieve MRD status < 10-4 lymphoblasts at the end of the Induction Cycle as assessed by quantitative immunoglobulin/T-cell receptor (Ig/TcR) polymerase chain reaction (PCR)
Timepoint [13] 0 0
29 months
Secondary outcome [14] 0 0
Minimal Residual Disease (MRD) Status in Subjects with Complete Response (CR), CR with Incomplete Recovery of Platelets (CRp), CR with Partial Hematological Recovery (CRh) or CR with Incomplete Hematological Recovery (CRi) - Proportion of subjects who achieve MRD status < 10-3 and < 10-4 lymphoblasts at the end of the Induction Cycle as assessed by quantitative immunoglobulin/T-cell receptor (Ig/TcR) polymerase chain reaction (PCR).
Timepoint [14] 0 0
29 months
Secondary outcome [15] 0 0
Number of Subjects who Experience a Stem Cell Transplant or Chimeric Antigen Receptor T Cell Therapy (CAR-T)
Timepoint [15] 0 0
29 months
Secondary outcome [16] 0 0
Phase 2: Number of Subjects who Experience a Clinically Significant Change from Baseline in Laboratory Analytes
Timepoint [16] 0 0
29 months
Secondary outcome [17] 0 0
Number of Subjects who Experience Complete Response (CR), CR with Incomplete Recovery of Platelets (CRp), or CR with Incomplete Hematological Recovery (CRi) After Consolidation Therapy in Subjects Aged = 12 Months at Screening
Timepoint [17] 0 0
Day 29 and 45
Secondary outcome [18] 0 0
Number of Subjects who Experience Complete Response (CR), CR with Incomplete Recovery of Platelets (CRp), or CR with Incomplete Hematological Recovery (CRi) After Consolidation Therapy in Subjects Aged = 12 Months at Screening
Timepoint [18] 0 0
Day 36 to 50
Secondary outcome [19] 0 0
Phase 2: Maximum Plasma Concentration (Cmax)
Timepoint [19] 0 0
29 months
Secondary outcome [20] 0 0
Phase 2: Area Under the Concentration-time Curve (AUC)
Timepoint [20] 0 0
29 months
Secondary outcome [21] 0 0
Phase 2: Half-life (t1/2) of Carfilzomib
Timepoint [21] 0 0
29 months

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.

2. Age = 1 month to < 21 years. Subjects = 18 years must have had their original
diagnosis at < 18 years of age.

3. Subjects must be diagnosed with relapsed or refractory relapsed ALL.

4. Subjects must have a documented first remission, = 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 = 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 = 5% leukemia
blasts in bone marrow) after having received a targeted B-cell immune therapy as
treatment for a prior relapse (eg, blinatumomab, inotuzumab or a CAR-T therapy) with
or without extramedullary disease. Subjects that received blinatumomab for treatment
of MRD positive disease during first remission or for primary induction failure to
achieve a first remission do not qualify.

6. Adequate liver function: bilirubin = 1.5 x upper limit of normal (ULN), alanine
aminotransferase (ALT) = 5 x ULN.

7. Adequate renal function: serum creatinine = 1.5 x ULN or glomerular filtration rate
(GFR) = 70 mL/min/1.73 m^2; or for children < 2 years of age = 50 mL/min/1.73 m^2.

8. Adequate cardiac function: shortening fraction = 30% or ejection fraction = 50%.

9. Karnofsky (subjects = 16 years of age) or Lansky (subjects 12 months to < 16 years of
age) performance status = 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 > 6 weeks per investigator's judgement at time of screening.

Phase 1b Key
Minimum age
1 Month
Maximum age
21 Years
Gender
Both males and females
Can healthy volunteers participate?
No
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. Prior treatment with a proteasome inhibitor (other than carfilzomib) within < 3 months
of enrollment or to which a subject did not respond (response is defined as bone
marrow with < 5% blasts).

3. Treatment with a chemotherapy regimen including a vinca alkaloid, steroid,
L-asparaginase, and anthracycline combination with or without other chemotherapy
agents within 2 months of enrollment (eg VXLD, VPLD, R3).

4. 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,

5. Autologous HSCT within 6 weeks prior to start of study treatment.

6. Allogeneic HSCT within 3 months prior to start of study treatment.

7. Active GVHD requiring systemic immune suppression.

8. < 30 days from discontinuation of immune suppressive therapy administered for the
treatment of acute or chronic GVHD.

9. Isolated extramedullary relapse.

10. 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.

11. < 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.

12. 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.

13. Down's syndrome.

14. Presence of another active cancer.

15. History of grade = 2 pancreatitis within 6 months to screening.

16. 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 > 4 weeks).

17. 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.

18. Active viral infection, including but not limited to 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.

19. Currently receiving treatment in another investigational device or product study, or <
14 days since ending treatment on another investigational device or product study.

20. Uncontrolled arrhythmias or screening ECG with corrected QT interval (QTc) of > 470
msec.

21. 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.

22. 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.

23. 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.

24. Female subjects of childbearing potential with a positive pregnancy test assessed at
Screening by a serum or urine pregnancy test.

25. 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.

26. 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.

27. 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Research Site - Randwick
Recruitment hospital [2] 0 0
Research Site - South Brisbane
Recruitment hospital [3] 0 0
Research Site - Parkville
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Minnesota
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Utah
Country [16] 0 0
United States of America
State/province [16] 0 0
Wisconsin
Country [17] 0 0
Austria
State/province [17] 0 0
Wien
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
Denmark
State/province [20] 0 0
Kobenhavn O
Country [21] 0 0
France
State/province [21] 0 0
Bordeaux Cedex
Country [22] 0 0
France
State/province [22] 0 0
Lille
Country [23] 0 0
France
State/province [23] 0 0
Paris
Country [24] 0 0
France
State/province [24] 0 0
Toulouse Cedex 9
Country [25] 0 0
France
State/province [25] 0 0
Vandoeuvre les Nancy
Country [26] 0 0
Israel
State/province [26] 0 0
Tel Hashomer
Country [27] 0 0
Italy
State/province [27] 0 0
Monza (MB)
Country [28] 0 0
Italy
State/province [28] 0 0
Roma
Country [29] 0 0
Netherlands
State/province [29] 0 0
Rotterdam
Country [30] 0 0
Spain
State/province [30] 0 0
Madrid
Country [31] 0 0
Switzerland
State/province [31] 0 0
Zuerich
Country [32] 0 0
United Kingdom
State/province [32] 0 0
Birmingham
Country [33] 0 0
United Kingdom
State/province [33] 0 0
London
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Manchester
Country [35] 0 0
United Kingdom
State/province [35] 0 0
Newcastle upon Tyne
Country [36] 0 0
United Kingdom
State/province [36] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amgen
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) - Study Design & Execution Collaborator
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Innovative Therapies For Children with Cancer Consortium
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

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 response (CR) of
carfilzomib in combination with vincristine, dexamethasone, PEG asparaginase, daunorubicin
(VXLD) at the end of induction therapy to an appropriate external control.
Trial website
https://clinicaltrials.gov/show/NCT02303821
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Amgen Call Center
Address 0 0
Country 0 0
Phone 0 0
866-572-6436
Fax 0 0
Email 0 0
medinfo@amgen.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02303821