Chemotherapy Followed by Donor White Blood Cells Plus Interleukin-2 in Treating Patients With Acute Myeloid or Lymphocytic Leukemia

Sponsor

Fred Hutchinson Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00005802

Collaborator

National Cancer Institute (NCI) (NIH)

Location

Duration (Months)

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Leukemia	Biological: aldesleukin Biological: filgrastim Biological: therapeutic allogeneic lymphocytes Drug: cytarabine Drug: etoposide Drug: fludarabine phosphate Drug: methotrexate Drug: mitoxantrone hydrochloride Drug: therapeutic hydrocortisone Radiation: radiation therapy	Phase 1/Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

Chemotherapy (CT) Followed by Donor Lymphocyte Infusion (DLI) Plus Interleukin 2 (IL-2) for Patients With Relapse Acute Myeloid or Lymphoid Leukemia After Allogeneic Hematopoietic Transplant

Study Start Date :

Jun 1, 1999

Actual Primary Completion Date :

Mar 1, 2005

Actual Study Completion Date :

Mar 1, 2005

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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