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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00003116
First received: November 1, 1999
Last updated: June 9, 2010
Last verified: June 2010
  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

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • 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)
Intervention Details:
    Biological: filgrastim
    Filgrastim (G-CSF) is administered subcutaneously twice a day beginning 3 hours after completion of cell infusion and continuing until blood counts recover.
    Drug: busulfan
    high-dose oral busulfan every 6 hours on days -8 to -5
    Drug: cyclophosphamide
    cyclophosphamide IV twice a day on days -4 and -3
    Drug: cyclosporine
    cyclosporine IV over 6 hours on day -1 and then 10 hours on day 0 for 2 doses (allogeneic only)
    Procedure: bone marrow ablation with stem cell support Procedure: peripheral blood stem cell transplantation
    Allogeneic peripheral blood progenitor cells IV are administered on day 0.
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.

  Eligibility

Ages Eligible for Study:   4 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003116

Locations
United States, Ohio
Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
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:
Leukemia
Lymphoma
Multiple Myeloma
Myelodysplastic Syndromes
Myelodysplastic-Myeloproliferative Diseases
Myeloproliferative Disorders
Neoplasms, Plasma Cell
Plasmacytoma
Preleukemia
Syndrome
Blood Protein Disorders
Bone Marrow Diseases
Cardiovascular Diseases
Disease
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Pathologic Processes
Precancerous Conditions
Vascular Diseases
Busulfan
Cyclophosphamide
Cyclosporine

ClinicalTrials.gov processed this record on October 21, 2014