High-Dose Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Hematologic Cancer

Sponsor

Case Comprehensive Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00003116

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

145

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving busulfan, cyclophosphamide, and filgrastim together with peripheral stem cell transplantation from a sibling donor works in treating patients with hematologic cancer.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Biological: filgrastim Drug: busulfan Drug: cyclophosphamide Drug: cyclosporine Procedure: bone marrow ablation with stem cell support Procedure: peripheral blood stem cell transplantation	Phase 2

Detailed Description

OBJECTIVES:

Determine the safety and feasibility of using allogeneic peripheral blood progenitor cell infusions obtained from normal histocompatible sibling donors for reconstituting bone marrow and immunologic function when given after high-dose busulfan/cyclophosphamide in patients with a hematologic malignancy.
Determine the efficacy of this treatment in these patients.
Determine the ability to mobilize hematopoietic progenitor cells from normal donors given filgrastim (G-CSF) by determining the hematopoietic progenitor cell content of allogeneic peripheral blood progenitor cell collections.
Determine the incidence of engraftment failures in these patients.
Determine the incidence of severe acute graft-versus-host disease in these patients.

OUTLINE: Patients receive high-dose oral busulfan every 6 hours on days -8 to -5, cyclophosphamide IV twice a day on days -4 and -3, and cyclosporine IV over 6 hours on day -1 and then 10 hours on day 0 for 2 doses (allogeneic only). Allogeneic peripheral blood progenitor cells IV are administered on day 0.

Filgrastim (G-CSF) is administered subcutaneously twice a day beginning 3 hours after completion of cell infusion and continuing until blood counts recover.

Patients are followed every month for 2 months, every 3 months for 6 months, and then every 6 months until disease progression.

PROJECTED ACCRUAL: A total of 40 patients will be accrued over a 15 month period.

Study Design

Study Type:

Interventional

Actual Enrollment :

66 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Allogeneic Peripheral Blood Progenitor Cell Transplantation Using Histocompatible Sibling-Matched Donor Cells After High-Dose Busulfan/Cyclophosphamide as Therapy for Hematologic Malignancies

Study Start Date :

May 1, 1997

Actual Primary Completion Date :

Mar 1, 2006

Actual Study Completion Date :

Jun 1, 2009

Outcome Measures

Primary Outcome Measures

Hematopoietic reconstitution measured daily during transplant [at months 2, 4, 7, and 10, and then every 6 months until disease progression]

Eligibility Criteria

Criteria

Ages Eligible for Study:

4 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically diagnosed:
Acute myeloid leukemia in first, second, or third complete remission or first or second early relapse
Acute lymphoblastic leukemia in first, second, or third complete remission or first or second early relapse
Hodgkin's lymphoma in second or third remission or first, second, or third relapse, or refractory
Non-Hodgkin's lymphoma in second or third remission or first, second, or third relapse, or refractory
Multiple myeloma and plasma cell leukemia in second or third remission or first, second, or third relapse, or refractory
Myelodysplastic syndrome deemed suitable for allogeneic bone marrow transplantation
No symptoms or signs of CNS involvement and CNS is disease free on lumbar puncture and brain CT scan
No active meningeal cancer

PATIENT CHARACTERISTICS:

Age:

4 to 55 (4 to 60 if donor is identical twin)

Performance status:

ECOG 0-2

Life expectancy:

Not specified

Hematopoietic:

Not specified

Hepatic:

SGOT/SGPT less than 3 times normal
Bilirubin less than 2.0 mg/dL

Renal:

Creatinine less than 2.1 mg/dL
Creatinine clearance at least 60 mL/min (no greater than 1.5 times normal for children under 40 kg)

Cardiovascular:

No uncontrolled hypertension
No uncontrolled congestive heart failure
No active angina pectoris requiring nitrates
At least 6 months since prior myocardial infarction
No major ventricular arrhythmia
Left ventricular ejection fraction at least 45% on MUGA

Pulmonary:

No severe or symptomatic restrictive or obstructive lung disease
FEV_1 greater than 50% of predicted
DLCO greater than 50% of predicted

Neurologic:

No severe central or peripheral neurologic abnormality

Other:

Must have HLA-A,B,C,D/DR identical sibling age 4 to 65, in good health
No insulin-dependent diabetes mellitus
No major thyroid or major adrenal dysfunction
No active infection
No other active malignancy
Not pregnant
HIV negative
HTLV-I and HTLV-II negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

No excessive anthracycline exposure, unless endomyocardial biopsy shows less than grade 2 drug effect and cardiac scan shows at least 50% ejection fraction
At least 1 year since prior autologous bone marrow or peripheral blood progenitor cell transplant or allogeneic bone marrow transplant