Chemotherapy in Treating Children With Recurrent Acute Myeloid Leukemia

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of idarubicin and cladribine in treating children who have recurrent acute myeloid leukemia.

Detailed Description
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OBJECTIVES: Determine the complete response rate in children with primary refractory or recurrent acute myeloid leukemia (AML) or secondary AML treated with idarubicin and cladribine. (Refractory AML stratum closed as of 4/3/01) (Secondary AML stratum closed as of 04/02/02) Compare the remission reinduction rates in children who relapse at 1 year or earlier vs more than 1 year from time of initial remission. Determine the toxic effects of this regimen in this patient population. OUTLINE: Patients are stratified according to disease characteristics (primary or secondary acute myeloid leukemia (AML) with first untreated relapse vs primary refractory AML). (Refractory AML stratum closed as of 4/3/01) (Secondary AML stratum closed as of 04/02/02) Patients receive idarubicin IV over 15 minutes on days 1-3, cladribine IV over 2 hours on days 1-5, and filgrastim (G-CSF) subcutaneously beginning on day 6 and continuing until blood counts have recovered for 2 days. Treatment repeats every 3 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response after completion of course 1 may proceed to other chemotherapy or bone marrow transplantation at the discretion of the protocol investigator. Patients with extramedullary disease may receive intrathecal chemotherapy or radiotherapy to symptomatic sites. Patients are followed every 3 months for 1 year, every 6 months for 4 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 51-102 patients will be accrued for this study within 3 years.

Official Title
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Idarubicin and Cladribine in Recurrent and Refractory Acute Myeloid Leukemia: A POG Phase II Study

Conditions
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Leukemia

Intervention / Treatment
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* Biological: filgrastim
* Drug: cladribine
* Drug: idarubicin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: One of the following diagnoses: Acute myeloid leukemia (AML) (FAB M0-M7) Secondary AML in first relapse (Secondary AML stratum closed as of 04/02/02) AML in primary induction failure (Refractory AML stratum closed as of 04/03/01) Myelodysplastic syndromes (MDS) (not related to Down syndrome) (MDS stratum closed as of 04/03/01) Extramedullary disease allowed Relapse more than 6 months after allogeneic or autologous bone marrow transplantation allowed PATIENT CHARACTERISTICS: Age: Under 21 at diagnosis Performance status: Karnofsky 50-100% (over 10 years) Lansky 50-100% (10 years and under) Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin less than 1.5 mg/dL ALT less than 3 times normal Renal: Creatinine less than 2 times normal Cardiovascular: Shortening fraction greater than 29% Ejection fraction greater than 55% with normal wall motion Other: No uncontrolled infection Not pregnant or nursing PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics Chemotherapy: At least 12 weeks since prior idarubicin and recovered At least 2 weeks since other prior chemotherapy and recovered Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified

Ages Eligible for Study
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Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1st Untreated Relapse for AML<br>Patients receive idarubicin IV over 15 minutes on days 1-3, cladribine IV over 2 hours on days 1-5, and filgrastim (G-CSF) subcutaneously beginning on day 6 and continuing until blood counts have recovered for 2 days. Treatment repeats every 3 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response after completion of course 1 may proceed to other chemotherapy or bone marrow transplantation at the discretion of the protocol investigator. Patients with extramedullary disease may receive intrathecal chemotherapy or radiotherapy to symptomatic sites. | Biological: filgrastim<br> <br> * Other names: NSC #614629;Drug: cladribine<br> <br> * Other names: NSC #105014);Drug: idarubicin<br> <br> * Other names: NSC#256439);|
| Experimental: Primary Refractory AML<br>Patients receive idarubicin IV over 15 minutes on days 1-3, cladribine IV over 2 hours on days 1-5, and filgrastim (G-CSF) subcutaneously beginning on day 6 and continuing until blood counts have recovered for 2 days. Treatment repeats every 3 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response after completion of course 1 may proceed to other chemotherapy or bone marrow transplantation at the discretion of the protocol investigator. Patients with extramedullary disease may receive intrathecal chemotherapy or radiotherapy to symptomatic sites. | Biological: filgrastim<br> <br> * Other names: NSC #614629;Drug: cladribine<br> <br> * Other names: NSC #105014);Drug: idarubicin<br> <br> * Other names: NSC#256439);|
| Experimental: MDS<br>Patients receive idarubicin IV over 15 minutes on days 1-3, cladribine IV over 2 hours on days 1-5, and filgrastim (G-CSF) subcutaneously beginning on day 6 and continuing until blood counts have recovered for 2 days. Treatment repeats every 3 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response after completion of course 1 may proceed to other chemotherapy or bone marrow transplantation at the discretion of the protocol investigator. Patients with extramedullary disease may receive intrathecal chemotherapy or radiotherapy to symptomatic sites. | Biological: filgrastim<br> <br> * Other names: NSC #614629;Drug: cladribine<br> <br> * Other names: NSC #105014);Drug: idarubicin<br> <br> * Other names: NSC#256439);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event Free Survival | EFS will be estimated by Kaplan-Meier31 method. Prognostic factor analyses will be performed descriptively due to the limited sample size. |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent childhood acute myeloid leukemia, childhood acute myeloblastic leukemia without maturation (M1), childhood acute myeloblastic leukemia with maturation (M2), childhood acute promyelocytic leukemia (M3), childhood acute myelomonocytic leukemia (M4), childhood acute monoblastic leukemia (M5a), childhood acute monocytic leukemia (M5b), childhood acute erythroleukemia (M6), childhood acute megakaryocytic leukemia (M7), childhood acute minimally differentiated myeloid leukemia (M0)