Ignite Creation Date:
2024-05-05 @ 5:02 PM
Last Modification Date:
2024-10-26 @ 9:27 AM
Study NCT ID:
NCT00372619
Status:
COMPLETED
Last Update Posted:
2017-06-05
First Post:
2006-09-06
Brief Title:
Clofarabine and Cytarabine in Treating Young Patients With Refractory or Relapsed Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia
Sponsor:
Childrens Oncology Group
Organization:
Childrens Oncology Group
Study Overview
Official Title:
A Phase III Study of CLOLAR Clofarabine IND 73 789 in Combination With Cytarabine in Pediatric Patients With RefractoryRelapsed Leukemia
Status:
COMPLETED
Status Verified Date:
2017-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
RATIONALE Drugs used in chemotherapy such as clofarabine and cytarabine work in different ways to stop the growth of cancer cells either by killing the cells or by stopping them from dividing Giving more than one drug combination chemotherapy may kill more cancer cells
PURPOSE This phase III trial is studying the side effects and best dose of clofarabine when given together with cytarabine and to see how well they work in treating young patients with refractory or relapsed acute myeloid leukemia or acute lymphoblastic leukemia Phase I closed to enrollment as of 091609
PURPOSE This phase III trial is studying the side effects and best dose of clofarabine when given together with cytarabine and to see how well they work in treating young patients with refractory or relapsed acute myeloid leukemia or acute lymphoblastic leukemia Phase I closed to enrollment as of 091609
Detailed Description:
OBJECTIVES
Primary
To define the overall response rate complete remission or remission without platelet recovery in young patients with relapsed or refractory acute myeloid leukemia AML or acute lymphoblastic leukemia ALL treated with clofarabine in combination with cytarabine
Secondary
To determine the safety profile and tolerability of clofarabine when given in combination with cytarabine in patients with and without prior stem cell transplantation
To identify apoptosis specific genes that are important in mediating response to clofarabine and cytarabine
To quantitate the level of human equilibrative nucleoside transporter proteins hENT1 and hENT2 and human concentrative nucleoside transporter proteins hCNT2 and hCNT3 in blasts of these patients
To determine gene expression profiles at study entry and at time of relapse in order to isolate profiles that may predict response and also to complement apoptosis specific protein arrays
To perform serial measurements of minimal residual disease MRD to provide an objective determination of the effectiveness of this treatment regimen and to correlate with post remission events relapse death
To perform FLT3ITD analysis to help determine the prevalence and clinical significance of this somatic mutation in patients with relapsed AML
OUTLINE This is a multicenter phase I dose-escalation study of clofarabine followed by a phase II study Patients are stratified according to disease acute lymphoblastic leukemia ALL vs acute myeloid leukemia AML Phase I closed to accrual as of 091609
Intrathecal CNS prophylaxis all patients with ALL and at physicians discretion for patients with AML or acute leukemia of ambiguous lineage Patients receive intrathecal IT cytarabine on day 0 of the first course of induction therapy Patients also receive IT methotrexate on day 1 of the second course of induction therapy and on day 1 of all courses of maintenance therapy
Induction therapy
Course 1 Patients receive cytarabine IV over 2 hours and clofarabine IV over 2 hours on days 1-5 Patients with 5 blasts ie M2 or M3 bone marrow at days 14-21 proceed immediately to course 2 of induction therapy Patients with 5 blasts ie M1 bone marrow may proceed to course 2 of induction therapy at blood count recovery or at day 42
Course 2 Patients receive clofarabine IV over 2 hours followed by cytarabine IV over 2 hours on days 1-5 After the second course of induction therapy patients with M2 or M3 bone marrow at days 14-21 are removed from the study Patients with M1 bone marrow proceed to maintenance therapy 14-42 days after the initiation of course 2
Maintenance therapy Patients receive clofarabine and cytarabine as in induction therapy Treatment repeats every 14-42 days for up to 10 courses in the absence of disease progression or unacceptable toxicity
Patients may undergo blood and bone marrow sample collection periodically for correlative laboratory studies
After completion of study therapy patients are followed periodically for up to 5 years
PROJECTED ACCRUAL A total of 87 patients will be accrued for this study
Primary
To define the overall response rate complete remission or remission without platelet recovery in young patients with relapsed or refractory acute myeloid leukemia AML or acute lymphoblastic leukemia ALL treated with clofarabine in combination with cytarabine
Secondary
To determine the safety profile and tolerability of clofarabine when given in combination with cytarabine in patients with and without prior stem cell transplantation
To identify apoptosis specific genes that are important in mediating response to clofarabine and cytarabine
To quantitate the level of human equilibrative nucleoside transporter proteins hENT1 and hENT2 and human concentrative nucleoside transporter proteins hCNT2 and hCNT3 in blasts of these patients
To determine gene expression profiles at study entry and at time of relapse in order to isolate profiles that may predict response and also to complement apoptosis specific protein arrays
To perform serial measurements of minimal residual disease MRD to provide an objective determination of the effectiveness of this treatment regimen and to correlate with post remission events relapse death
To perform FLT3ITD analysis to help determine the prevalence and clinical significance of this somatic mutation in patients with relapsed AML
OUTLINE This is a multicenter phase I dose-escalation study of clofarabine followed by a phase II study Patients are stratified according to disease acute lymphoblastic leukemia ALL vs acute myeloid leukemia AML Phase I closed to accrual as of 091609
Intrathecal CNS prophylaxis all patients with ALL and at physicians discretion for patients with AML or acute leukemia of ambiguous lineage Patients receive intrathecal IT cytarabine on day 0 of the first course of induction therapy Patients also receive IT methotrexate on day 1 of the second course of induction therapy and on day 1 of all courses of maintenance therapy
Induction therapy
Course 1 Patients receive cytarabine IV over 2 hours and clofarabine IV over 2 hours on days 1-5 Patients with 5 blasts ie M2 or M3 bone marrow at days 14-21 proceed immediately to course 2 of induction therapy Patients with 5 blasts ie M1 bone marrow may proceed to course 2 of induction therapy at blood count recovery or at day 42
Course 2 Patients receive clofarabine IV over 2 hours followed by cytarabine IV over 2 hours on days 1-5 After the second course of induction therapy patients with M2 or M3 bone marrow at days 14-21 are removed from the study Patients with M1 bone marrow proceed to maintenance therapy 14-42 days after the initiation of course 2
Maintenance therapy Patients receive clofarabine and cytarabine as in induction therapy Treatment repeats every 14-42 days for up to 10 courses in the absence of disease progression or unacceptable toxicity
Patients may undergo blood and bone marrow sample collection periodically for correlative laboratory studies
After completion of study therapy patients are followed periodically for up to 5 years
PROJECTED ACCRUAL A total of 87 patients will be accrued for this study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| CDR0000494654 | OTHER | None | None |
| NCI-2009-00319 | OTHER | None | None |
| COG-AAML0523 | OTHER | Childrens Oncology Group | None |