Trial Information

A Phase I Trial of Combined Chemotherapy and Donor Lymphocyte Infusion for Aggressive Hematologic Malignancies in Relapse After Allogeneic Bone Marrow Transplantation

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.