Clinical trial NCT00003243: Combination Chemotherapy Plus Infusion of White Blood Cells in Treating Patients With Hematologic Cancer
Official title: A Phase I Trial of Combined Chemotherapy and Donor Lymphocyte Infusion for Aggressive Hematologic Malignancies in Relapse After Allogeneic Bone Marrow Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia
Lymphoma
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Keywords: recurrent childhood acute lymphoblastic leukemia
recurrent childhood lymphoblastic lymphoma
recurrent childhood acute myeloid leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
acute undifferentiated leukemia
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
secondary acute myeloid leukemia
previously treated myelodysplastic syndromes
recurrent childhood small noncleaved cell lymphoma
recurrent childhood large cell lymphoma
childhood chronic myelogenous leukemia
atypical chronic myeloid leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
childhood myelodysplastic syndromes
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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. White blood cells from donors may be able to kill cancer cells in patients who have hematologic cancer that has recurred following bone marrow transplantation.

PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus infusion of donated white blood cells in treating patients who have hematologic cancer that has recurred after bone marrow transplantation.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Ephraim J. Fuchs, MD
role: STUDY_CHAIR
References: