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

NCT ID: NCT00003116

Last Updated: 2010-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1997-05-31
• Study Completion Date: 2009-06-30

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.

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.

Conditions

Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

filgrastim

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

Intervention Type: BIOLOGICAL

busulfan

high-dose oral busulfan every 6 hours on days -8 to -5

Intervention Type: DRUG

cyclophosphamide

cyclophosphamide IV twice a day on days -4 and -3

Intervention Type: DRUG

cyclosporine

cyclosporine IV over 6 hours on day -1 and then 10 hours on day 0 for 2 doses (allogeneic only)

Intervention Type: DRUG

bone marrow ablation with stem cell support

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Allogeneic peripheral blood progenitor cells IV are administered on day 0.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

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

Chemotherapy:

• At least 3 weeks since prior chemotherapy
• No prior excessive carmustine and bleomycin

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 3 weeks since prior radiotherapy

Surgery:

• Not specified

Other:

• No concurrent nitroglycerin for angina pectoris
• No concurrent anti-arrhythmic drugs for major ventricular dysrhythmias

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Case Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

Principal Investigators

Hillard M. Lazarus, MD

Role: STUDY_CHAIR

Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center

Locations

Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

P30CA043703

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CASE-CWRU-1995

Identifier Type: -

Identifier Source: secondary_id

NCI-G97-1354

Identifier Type: -

Identifier Source: secondary_id

CASE1995T

Identifier Type: OTHER

Identifier Source: secondary_id

CWRU1995T

Identifier Type: -

Identifier Source: org_study_id