Chemotherapy in Treating Children With Recurrent Acute Myeloid Leukemia

Children's Oncology Group

Status and phase: Completed; Phase 2

Conditions: Leukemia

Treatments: Drug: cladribine; Drug: idarubicin; Biological: filgrastim

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00003178

CDR0000065993 (Other Identifier)

COG-P9720 (Other Identifier)

9720

POG-9720 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 120 patients

Sex: All

Ages: Under 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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120 participants in 3 patient groups

1st Untreated Relapse for AML

Experimental group

Description:

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.

Treatment:

Biological: filgrastim

Drug: idarubicin

Drug: cladribine

Primary Refractory AML

Experimental group

Description:

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.

Treatment:

Biological: filgrastim

Drug: idarubicin

Drug: cladribine

MDS

Experimental group

Description:

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.

Treatment:

Biological: filgrastim

Drug: idarubicin

Drug: cladribine