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Bone Marrow Transplantation in Treating Patients With Hematologic Cancer
This study has been completed.
First Received: June 2, 2000   Last Updated: February 6, 2009   History of Changes
Sponsors and Collaborators: Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00005854
  Purpose

RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy used to kill tumor cells.

PURPOSE: Phase II trial to study the effectiveness of bone marrow transplantation in treating patients who have hematologic cancer.


Condition Intervention Phase
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Drug: cyclophosphamide
Drug: cyclosporine
Drug: methotrexate
Procedure: allogeneic bone marrow transplantation
Procedure: in vitro-treated bone marrow transplantation
Radiation: radiation therapy
Phase II

Genetics Home Reference related topics: aceruloplasminemia hemophilia
MedlinePlus related topics: Bone Marrow Transplantation Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Lymphoma Multiple Myeloma Radiation Therapy
Drug Information available for: Cyclophosphamide Methotrexate Cyclosporine Cyclosporin
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: Transplantation of HLA Haploidentical Marrow Cells After Ex Vivo Exposure to Recipient Alloantigen in Presence of CTLA4-Ig - A Phase II Study of Tolerance Induction in Donor T Cells by Blockade of the CD80/CD86:CD28 Costimulatory Signal

Further study details as provided by National Cancer Institute (NCI):

Study Start Date: December 1999
Detailed Description:

OBJECTIVES: I. Determine the incidence and severity of acute graft versus host disease after transplantation of HLA haploidentical bone marrow preincubated with alloantigen and CTLA4-Ig ex vivo in patients with hematologic malignancies. II. Determine the engraftment rate with this treatment regimen in these patients. III. Determine the safety of this treatment regimen in these patients. IV. Determine the incidence of infection and relapse after this treatment regimen in these patients. V. Determine whether host specific tolerance develops in these patients after receiving this treatment regimen.

OUTLINE: This is a multicenter study. Patients undergo leukapheresis to collect white blood cells which are incubated with donor bone marrow cells in the presence of CTLA4-Ig for 36 hours. Patients undergo total body irradiation on days -7, -6, -5, and -4 and receive cyclophosphamide IV on days -3 and -2.

Patients with acute lymphocytic leukemia, prior lymphoid blast crisis chronic myelogenous leukemia, high grade non-Hodgkin's leukemia (NHL), intermediate grade NHL with prior marrow or extramedullary disease, or prior CNS leukemia receive 2 doses of methotrexate intrathecally prior to bone marrow transplantation, and 4-6 doses following. Patients receive bone marrow transplantation on day 0; methotrexate IV on days 1, 3, 6, and 11; and cyclosporine IV on days -1 to 50. Patients are followed weekly for 1 month, monthly for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study over 1-2 years.

  Eligibility

Ages Eligible for Study:   up to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS: Any of the following hematologic malignancies: Acute myelogenous leukemia in second or greater remission or relapse High risk acute lymphoblastic leukemia First complete remission with high risk cytogenetics [e.g., t(9;22), t(8;14), or t(4;11)] or slow early response OR Any second or greater remission OR Relapse or induction failure Relapsed non-Hodgkin's lymphoma (NHL) with chemotherapy sensitive disease Multiple myeloma with chemotherapy sensitive disease Chronic lymphocytic leukemia with chemotherapy sensitive disease Myelodysplastic syndrome Chronic myelogenous leukemia (CML) in accelerated phase, blast phase, or remission after blast phase Juvenile CML Patients must have haploidentical donors and meet the following criteria: Lack an HLA A, B, and DR matched related donor Lack an HLA A, B, DRB1 matched or single allele mismatched unrelated donor or for whom the following apply: High likelihood of rapid disease progression while an unrelated donor search is in progress AND Review of the patient HLA typing, gene frequency, results of the preliminary search and the donor pool suggest that a donor will not be found within a suitable time frame Lack an HLA A, B, DRB1 matched cord blood unit or lack a cord blood unit that has an adequate cell dose and is mismatched for 1-2 HLA A, B, DRB1 Do not have an indication for autologous transplant, including patients with NHL or multiple myeloma who are not eligible for autologous transplant Negative antidonor antibody crossmatch

PATIENT CHARACTERISTICS: Age: Under 51 Performance status: Not specified Life expectancy: No patients with life expectancy severely limited by diseases other than malignancy Hematopoietic: See Disease Characteristics Hepatic: AST no greater than 2 times normal Renal: Creatinine no greater than 2 times normal OR Creatinine clearance at least 50% for age, weight, and height Cardiovascular: No cardiac insufficiency requiring treatment No symptomatic coronary artery disease Pulmonary: No severe hypoxemia pO2 less than 70 mm Hg with decreased DLCO less than 70% predicted OR No mild hypoxemia pO2 less than 80 mm Hg with severely decreased DLCO less than 60% predicted Other: HIV negative Not pregnant or nursing Fertile patients must use effective contraception during and for one year after study No leukoencephalopathy

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Not specified Endocrine therapy: Not specified Radiotherapy: No more than 3,000 cGy prior radiotherapy to brain No more than 1,500 cGy prior radiotherapy to chest or abdomen Surgery: Not specified

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005854

Locations
United States, Maryland
Johns Hopkins Oncology Center
Baltimore, Maryland, United States, 21287
United States, Massachusetts
University of Massachusetts Memorial Medical Center
Worcester, Massachusetts, United States, 01655
United States, South Carolina
University of South Carolina School of Medicine
Columbia, South Carolina, United States, 29203
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Study Chair: Ann E. Woolfrey, MD Fred Hutchinson Cancer Research Center
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000067879, FHCRC-1457.00, NCI-H00-0059
Study First Received: June 2, 2000
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00005854     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent childhood acute lymphoblastic leukemia
refractory multiple myeloma
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
recurrent childhood lymphoblastic lymphoma
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
recurrent childhood acute myeloid leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
refractory chronic lymphocytic leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
meningeal chronic myelogenous 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 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
secondary acute myeloid leukemia

Study placed in the following topic categories:
Blast Crisis
Cyclosporine
Miconazole
Lymphoma, Mantle-Cell
Mantle Cell Lymphoma
Cyclosporins
Follicular Lymphoma
Preleukemia
Acute Myelocytic Leukemia
Hemorrhagic Disorders
Acute Myeloid Leukemia, Adult
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasm Metastasis
Methotrexate
Lymphoma, Large B-Cell, Diffuse
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Hematologic Diseases
Blood Coagulation Disorders
Leukemia, Myeloid
Multiple Myeloma
Folic Acid
B-cell Lymphomas
Leukemia, Myeloid, Accelerated Phase
Chronic Myelogenous Leukemia
Lymphoma, Non-Hodgkin
Antimetabolites
Acute Lymphoblastic Leukemia, Childhood
Leukemia, Lymphoid
Immunologic Factors

Additional relevant MeSH terms:
Anti-Infective Agents
Cyclosporine
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Cyclosporins
Preleukemia
Pathologic Processes
Hemorrhagic Disorders
Therapeutic Uses
Abortifacient Agents
Methotrexate
Cardiovascular Diseases
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors
Immunoproliferative Disorders
Immune System Diseases
Hematologic Diseases
Abortifacient Agents, Nonsteroidal
Multiple Myeloma
Neoplasms
Antimetabolites
Precancerous Conditions
Immunologic Factors
Blood Protein Disorders
Antineoplastic Agents
Paraproteinemias
Cyclophosphamide
Reproductive Control Agents
Hemostatic Disorders

ClinicalTrials.gov processed this record on May 07, 2009