RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Interleukin-2 may stimulate a person's white blood cells to kill leukemia cells. Treating donor white blood cells with interleukin-2 in the laboratory may help them kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of interleukin-2 when given after chemotherapy and donor white blood cells and to see how well they work in treating patients with acute myeloid leukemia or acute lymphoid leukemia.

Condition	Treatment or Intervention	Phase
adult acute lymphoblastic leukemia adult acute myeloid leukemia childhood acute lymphoblastic leukemia childhood acute myeloid leukemia	Drug: allogeneic lymphocytes  Drug: cytarabine  Drug: etoposide  Drug: filgrastim  Drug: fludarabine  Drug: hydrocortisone  Drug: interleukin-2  Drug: methotrexate  Drug: mitoxantrone  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: interleukin therapy  Procedure: leukocyte therapy  Procedure: peripheral blood lymphocyte therapy  Procedure: radiation therapy	Phase I Phase II

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose of interleukin-2 following donor lymphocyte infusion and chemotherapy in patients with relapsed acute myeloid or lymphoid leukemia after allogeneic peripheral blood stem cell transplantation.
• Determine the toxicity and efficacy of this regimen in these patients.

OUTLINE: This is a dose escalation study of interleukin-2 (IL-2). Patients are stratified according to disease status after chemotherapy (acute myeloid leukemia (AML) in complete remission (CR) vs acute lymphoid leukemia (ALL) or AML not in CR).

Patients receive one of three induction chemotherapy regimens, depending on type of leukemia, prior treatment, and response.

• Regimen 1: Patients receive high dose cytarabine IV over 2 hours twice a day on days 1, 3, and 5.
• Regimen 2: Patients receive mitoxantrone IV over 15 minutes and etoposide IV over 30 minutes on days 1-5.
• Regimen 3: Patients receive fludarabine IV over 30 minutes on days 1-5, cytarabine IV over 2 hours on days 1-4, and filgrastim (G-CSF) subcutaneously beginning on day 1 and continuing until blood counts recover. Patients with extramedullary relapse receive local radiotherapy. Patients with ALL or CNS relapse receive intrathecal methotrexate with or without hydrocortisone and cytarabine.

Patients receive one donor lymphocyte infusion IV over 15-30 minutes within 28-60 days after starting chemotherapy. On the same day, IL-2 IV is administered over 24 hours for 5 days. After 2 days rest, IL-2 is again administered continuously for 10 days.

Cohorts of 5 patients receive escalating doses of IL-2 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 2 of 5 patients experience dose limiting toxicities. Up to 40 patients are treated at the MTD.

Patients are followed monthly for 3 months, and then every 6 months thereafter.

PROJECTED ACCRUAL: Approximately 11-15 patients per year will be accrued for this study.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Relapsed acute myeloid leukemia or acute lymphoid leukemia after allogeneic peripheral blood stem cell transplantation (PBSCT), documented by 1 of the following:
• Morphologic relapse defined as 1 or more of the following:
• Peripheral blasts in absence of growth factor therapy
• Bone marrow blasts greater than 5% of nucleated cells
• Extramedullary (CNS, testicular, or other sites)
• Flow cytometric relapse defined as appearance in peripheral blood or bone marrow of cells with abnormal immunophenotype consistent with leukemia recurrence and noted at pretransplant
• Cytogenetic relapse defined as:
• Appearance in 1 or more metaphases from bone marrow or peripheral blood cells of nonconstitutional cytogenetic abnormality noted in at least 1 cytogenetic study performed prior to transplant OR
• New abnormality known to be associated with leukemia
• Allogeneic PBSCT from related (HLA identical and 1 antigen mismatch) OR unrelated (match) donor
• Must have achieved complete remission after PBSCT
• Current donor must be same as prior donor
• Age 10 and over

PATIENT CHARACTERISTICS: Age:

• Not specified

Performance status:

• SWOG 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Bilirubin no greater than 2.0 mg/dL

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• No congestive heart failure requiring diuretics
• No uncontrolled arrhythmia

Pulmonary:

• No pulmonary dysfunction requiring oxygen therapy
• No pneumonia or severe obstruction
• FEV_1 at least 50% of predicted OR no greater than 50% decline from baseline
• No severe restrictive lung disease (total lung capacity less than 60% or 50% declined from baseline) not due to leukemia

Other:

• No sepsis, aspergillosis, or other active infection

PRIOR CONCURRENT THERAPY: Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• No concurrent cyclosporine or tacrolimus during induction chemotherapy

Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109-1024,  United States; Recruiting

Study chairs or principal investigators

Mary E. D. Flowers, MD,  Study Chair,  Fred Hutchinson Cancer Research Center   

Study ID Numbers:  CDR0000067777; FHCRC-1380.00; NCI-H00-0057; NCT00005802
Record last reviewed:  June 2000
Last Updated:  March 3, 2005
Record first received:  June 2, 2000
ClinicalTrials.gov Identifier:  NCT00005802
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08