High-Dose Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Hematologic Cancer
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Purpose
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 | Intervention | 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 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: 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 |
- Hematopoietic reconstitution measured daily during transplant [ Time Frame: at months 2, 4, 7, and 10, and then every 6 months until disease progression ] [ Designated as safety issue: No ]
| Enrollment: | 66 |
| Study Start Date: | May 1997 |
| Study Completion Date: | June 2009 |
| Primary Completion Date: | March 2006 (Final data collection date for primary outcome measure) |
-
Biological: filgrastim
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.
Eligibility| Ages Eligible for Study: | 4 Years to 55 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| United States, Ohio | |
| Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center | |
| Cleveland, Ohio, United States, 44106-5065 | |
| Study Chair: | Hillard M. Lazarus, MD | Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center |
More Information
Additional Information:
No publications provided
| Responsible Party: | Hillard Lazarus, MD, Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center |
| ClinicalTrials.gov Identifier: | NCT00003116 History of Changes |
| Other Study ID Numbers: | CWRU1995T, P30CA043703, CASE-CWRU-1995, NCI-G97-1354, CASE1995T |
| Study First Received: | November 1, 1999 |
| Last Updated: | June 9, 2010 |
| Health Authority: | United States: Federal Government |
Keywords provided by Case Comprehensive Cancer Center:
|
recurrent childhood acute lymphoblastic leukemia recurrent adult Hodgkin lymphoma refractory multiple myeloma recurrent childhood lymphoblastic lymphoma recurrent childhood acute myeloid leukemia recurrent adult acute myeloid leukemia recurrent adult acute lymphoblastic leukemia adult acute myeloid leukemia in remission adult acute lymphoblastic leukemia in remission childhood acute myeloid leukemia in remission childhood acute lymphoblastic leukemia in remission recurrent/refractory childhood Hodgkin lymphoma recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma |
recurrent adult diffuse small cleaved cell lymphoma recurrent adult diffuse mixed cell lymphoma recurrent adult diffuse large cell lymphoma recurrent adult immunoblastic large cell lymphoma recurrent adult lymphoblastic lymphoma recurrent adult Burkitt lymphoma de novo myelodysplastic syndromes previously treated myelodysplastic syndromes secondary myelodysplastic syndromes recurrent childhood small noncleaved cell lymphoma recurrent childhood large cell lymphoma recurrent mantle cell lymphoma atypical chronic myeloid leukemia myelodysplastic/myeloproliferative disease, unclassifiable recurrent marginal zone lymphoma |
Additional relevant MeSH terms:
|
Neoplasms Leukemia Lymphoma Multiple Myeloma Neoplasms, Plasma Cell Plasmacytoma Myelodysplastic Syndromes Preleukemia Myeloproliferative Disorders Myelodysplastic-Myeloproliferative Diseases Neoplasms by Histologic Type Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases |
Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Bone Marrow Diseases Precancerous Conditions Busulfan Cyclophosphamide Cyclosporins Cyclosporine Lenograstim Immunosuppressive Agents |
ClinicalTrials.gov processed this record on May 16, 2013