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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01186328




Registration number
NCT01186328
Ethics application status
Date submitted
19/08/2010
Date registered
23/08/2010
Date last updated
1/02/2024

Titles & IDs
Public title
EZN-3042 Administered With Re-induction Chemotherapy in Children With Relapsed Acute Lymphoblastic Leukemia (ALL)
Scientific title
A Phase I Study Evaluating the Safety, Tolerability and Biological Activity of EZN-3042, a Survivin mRNA Antagonist, Administered With Re-induction Chemotherapy in Children With Relapsed Acute Lymphoblastic Leukemia (ALL)
Secondary ID [1] 0 0
T2009-007
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphoblastic Leukemia, Acute 0 0
Lymphoblastic Leukemia, Acute, Childhood 0 0
Leukemia, Lymphoblastic, Acute, T Cell 0 0
Leukemia, Lymphoblastic, Acute 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
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - EZN-3042
Treatment: Drugs - Cytarabine
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Prednisone
Treatment: Drugs - Vincristine
Treatment: Drugs - PEG-asparaginase
Treatment: Drugs - Methotrexate
Treatment: Drugs - Hydrocortisone

Experimental: Single Arm - Patients will receive 2 doses of EZN-3042 (and intrathecal cytarabine, conditionally) prior to initiating systemic therapy with vincristine, doxorubicin, prednisone and PEG-asparaginase. Patients with CNS 1 or 2 will also receive intrathecal methotrexate, and patients with CNS 3 will also receive triple intrathecal therapy (methotrexate, hydrocortisone, and cytarabine).


Treatment: Drugs: EZN-3042
Dose will be assigned at study entry. To be given as a 2 hour intravenous infusion on days -5, -2, 8, 15, 22 and 29. Dose levels: L0 (level zero): 1.5 mg/kg, L1: 2.5 mg/kg, L2: 5 mg/kg, L3: 6.5 mg/kg

Treatment: Drugs: Cytarabine
Given intrathecally on day -6. Patients who may have received intrathecal chemotherapy within 7 days of day 0 as part of their prior maintenance chemotherapy (e.g. before the diagnosis of relapse) or as part of the diagnostic workup will not receive this dose of IT cytarabine. If given, dose is defined by age:

1-1.99 years: 30 mg 2-2.99 years: 50 mg

Greater than or equal to 3 years: 70 mg.

Cytarabine is also part of the triple intrathecal therapy given to CNS 3 patients on Days 8, 15, 22 and 29. Dose is defined by age:

1. - 1.99 years: 16 mg
2. - 2.99 years: 20 mg
3. - 8.99 years: 24 mg

Greater than or equal to 9 years: 30 mg

Treatment: Drugs: Doxorubicin
60 mg/m2/day given intravenous infusion (IV) over 15 minutes on day 1.

Treatment: Drugs: Prednisone
40 mg/m2/day divided BID or TID given orally on days 1 through 29. For patients who are unable to tolerate prednisone orally, substitute IV methylprednisolone at 80% of the oral prednisone dose.

Treatment: Drugs: Vincristine
1.5 mg/m2/day (maximum dose 2 mg) given intravenous push over 1 minute or infusion via mini-bag as per institutional policy on days 1, 8, 15 and 22.

Treatment: Drugs: PEG-asparaginase
2500 IU/m2 intramuscular injection on days 2, 9, 16, 23. If available, Erwinia L-asparaginase may be substituted for pegaspargase in patients with clinically significant prior allergies to pegaspargase.

Treatment: Drugs: Methotrexate
Given intrathecally to patients with CNS1 or CNS2 disease at the dose defined by age below on days 15 and 36:

1-1.99 years: 8 mg 2-2.99 years: 10 mg 3-8.99 years: 12 mg

Greater than or equal to 9 years: 15 mg

Given as part of the Triple intrathecal therapy to patients with CNS 3 disease at the doses defined by age below on days 8, 15, 22 and 29:

1. - 1.99 years: 8 mg
2. - 2.99 years: 10 mg
3. - 8.99 years: 12 mg

Greater than or equal to 9 years: 15 mg

Treatment: Drugs: Hydrocortisone
Given as part of the Triple intrathecal therapy to patients with CNS 3 disease at the doses defined by age below on days 8, 15, 22 and 29:

1. - 1.99 years: 8 mg
2. - 2.99 years: 10 mg
3. - 8.99 years: 12 mg

Greater than or equal to 9 years: 15 mg
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum Tolerated Dose of EZN-3042
Timepoint [1] 0 0
2 months
Secondary outcome [1] 0 0
Number of Participants Who Showed a Decrease From Day -6 in Survivin Transcript Expression After EZN-3042 Administration
Timepoint [1] 0 0
Day -6 to Day 0

Eligibility
Key inclusion criteria
* Patients must be =1 and = 21 years of age when originally diagnosed with acute lymphoblastic leukemia (ALL).
* Patients must have relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL) with =25% blasts in the bone marrow (M3), with or without extramedullary disease.
* Patients may have central nervous system 1, 2 or 3 disease.
* Karnofsky Performance Level = 50 for patients > 10 years of age and Lansky = 50 for patients = 10 years of age.
* Patients must have had 2 or more prior therapeutic attempts defined as:

* Relapse after going into remission from re-induction for the first or subsequent relapse (ie: 2nd , 3rd, 4th...relapse), or
* Refractory disease after first or greater relapse and a single re-induction attempt. *Please note, Enrollment will be restricted to at most one refractory patient in each cohort of 3 patients per dose level.
* Patients with ALL who are refractory to frontline induction therapy are not eligible.
* Patients who relapse while receiving standard ALL maintenance chemotherapy will not be required to have a waiting period before entry onto this study.
* Patients who relapse when they are not receiving standard ALL maintenance therapy must have fully recovered from grade 3 or 4 toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
* Cytotoxic Therapy: It must be at least 14 days since the completion of cytotoxic therapy (excluding hydroxyurea) at the time of study enrollment.
* Hematopoietic Stem Cell Transplant (HSCT): Patients who have experienced their relapse after a HSCT are eligible, provided they have no evidence of active Graft-versus-Host Disease (GVHD) and are at least 120 days post-transplant at the time of enrollment.
* Prior anthracycline exposure: Patients must have = 400 mg/m2 lifetime exposure of anthracycline chemotherapy.
* Biologic (anti-neoplastic) therapy: It must be at least 7 days since the completion of therapy with a biologic agent at the time of study enrollment. For agents that have known adverse events occurring 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur.
* Patients must have a calculated creatinine clearance or radioisotope GRF = 70mL/min/1.73m2 OR a normal serum creatinine based on the institutional normal values according to age.
* Patient's ALT must be < 5 x institutional upper limit of norm (ULN), unless the elevation is suspected to be disease-related.
* Patient's total bilirubin must be = 1.5 x ULN.
* Patient's serum albumin must be = 2 g/dL.
* Patient must have prothrombin time (PT), partial thromboplastin time (PTT) and international normalized ratio (INR) = 1.5 times the ULN.
* Patient must have a shortening fraction = 27% by echocardiogram or an ejection fraction = 45% by gated nucleotide study.
* Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed prior to enrollment.
* Female patients with infants must agree not to breastfeed their infants while on this study.
* Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study.
Minimum age
1 Year
Maximum age
21 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Patients with Down syndrome are excluded.
* Patients with B-cell ALL (L3 morphology or evidence of myc translocation by molecular or cytogenetic technique) are not eligible
* Patients who cannot receive asparaginase on this study due to prior pancreatitis, stroke or other toxicity are not eligible.

* Patients with clinically significant prior allergies to PEG asparaginase are eligible if Erwinia L-asparaginase can be substituted. The study will not supply Erwinia.
* Patients who initially receive asparaginase, but must discontinue due to toxicity, remain eligible.
* Patients with documented active and uncontrolled infection at the time of study entry are not eligible.
* Patient will be excluded if they are currently receiving other investigational drugs.
* Patients will be excluded if they are taking strong CYP3A4 inducers or inhibitors.
* Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period.
* Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/08/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
10/01/2012
Sample size
Target
Accrual to date
Final
6
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Sydney
Recruitment postcode(s) [1] 0 0
- Sydney
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
Maryland
Country [3] 0 0
United States of America
State/province [3] 0 0
Minnesota
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Tennessee

Funding & Sponsors
Primary sponsor type
Other
Name
Therapeutic Advances in Childhood Leukemia Consortium
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Enzon Pharmaceuticals, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Elizabeth Raetz, MD
Address 0 0
NYU Langone Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

TypeCitations or Other Details
Journal Raetz EA, Morrison D, Romanos-Sirakis E, Gaynon P,... [More Details]

Results are available at https://clinicaltrials.gov/study/NCT01186328