Combination Chemotherapy Plus Infusion of White Blood Cells in Treating Patients With Hematologic Cancer

OBJECTIVES:

• Determine the maximum tolerated dose of doxorubicin HCl liposome when combined with etoposide, cyclophosphamide, and allogeneic donor lymphocyte infusion with or without interleukin-2 after allogeneic bone marrow transplantation in patients with relapsed or persistent aggressive hematologic malignancies.

OUTLINE: This is a partially randomized, dose-escalation study of doxorubicin HCl liposome (LipoDox).

Patients enter 1 of 4 cohorts.

• Cohort 1: Three to six patients receive induction comprising etoposide IV over 1 hour on days 1-3, cyclophosphamide IV over 1-2 hours on day 8, and allogeneic donor lymphocyte infusion on day 10. Filgrastim (G-CSF) is administered subcutaneously (SC) or IV daily beginning on day 10 and continuing until blood counts recover.
• Cohort 2: In the absence of dose-limiting toxicity (DLT) on cohort 1, 3-6 patients receive treatment as in cohort 1 and LipoDox IV over 2 hours on day 1.
• Cohort 3: In the absence of DLT on cohort 2, 3-6 patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive treatment as in cohort 1 plus a higher dose of LipoDox IV over 2 hours on day 1.
• Arm II: Patients receive treatment as in cohort 1 and interleukin-2 (IL-2) SC on days 10-12.

If DLT is reached on cohort 2, 3-6 patients receive treatment as in arm II.

• Cohort 4: In the absence of DLT on arms I and II, patients receive treatment as in cohort 1, LipoDox as in arm I, and IL-2 as in arm II.

Cohorts of 3-6 patients receive escalating doses of LipoDox until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience DLT.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 12-15 patients will be accrued for this study within 12-18 months.

DISEASE CHARACTERISTICS:

• Diagnosis of relapsed or persistent acute leukemia, myelodysplasia, aggressive non-Hodgkin's lymphoma (NHL), or chronic myeloid leukemia in transformed phase (accelerated phase or blast crisis) after allogeneic bone marrow transplantation (BMT)
• Aggressive NHL defined as diffuse mixed, diffuse large cell, diffuse small noncleaved cell, and lymphoblastic histologies
• No active acute graft versus host disease (GVHD) or extensive chronic GVHD

PATIENT CHARACTERISTICS:

Age:

• Not specified

Performance status:

• ECOG 0-2

Life expectancy:

• More than 4 weeks

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• No severe psychiatric illness or mental deficiencies

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• At least 6 months since prior allogeneic BMT
• No other concurrent interleukin-2
• No other concurrent immunomodulatory medication (e.g., interferon)

Chemotherapy:

• Not specified

Endocrine therapy:

• No concurrent steroids

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• No concurrent immunosuppressive medication (e.g., cyclosporine) for GVHD