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Bone Marrow Transplantation With Specially Treated Bone Marrow in Treating Patients With Hematologic Cancer That Has Not Responded to Previous Therapy
This study is ongoing, but not recruiting participants.
First Received: July 5, 2000   Last Updated: February 6, 2009   History of Changes
Sponsors and Collaborators: Dana-Farber Cancer Institute
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00005988
  Purpose

RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill tumor cells. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Treatment of the donor bone marrow with the patient's white blood cells and a monoclonal antibody may prevent this from happening.

PURPOSE: Phase I trial to study the effectiveness of bone marrow transplantation with specially treated bone marrow in treating patients who have hematologic cancer that has not responded to previous therapy.


Condition Intervention Phase
Graft Versus Host Disease
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Drug: cyclophosphamide
Drug: cyclosporine
Drug: leucovorin calcium
Drug: methotrexate
Drug: methylprednisolone
Procedure: in vitro-treated bone marrow transplantation
Radiation: radiation therapy
Phase I

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 Leucovorin Methotrexate Citrovorum factor Cyclosporine Cyclosporin Methylprednisolone Leucovorin Calcium Folinic acid calcium salt pentahydrate
U.S. FDA Resources
Study Type: Interventional
Study Design: Supportive Care
Official Title: A Phase I Open-Label, Safety Study of Haploidentical Bone Marrow Transplantation (BMT) After Ex Vivo Treatment of Bone Marrow With Anti-B7.1 and Anti-B7.2 Antibodies

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

Study Start Date: February 2000
Detailed Description:

OBJECTIVES: I. Determine if patients with refractory, high risk hematologic malignancies or bone marrow failure who receive HLA haploidentical bone marrow treated with anti-B7 antibody have normal engraftment. II. Determine if these patients are free of hyperacute graft versus host disease (GVHD), defined as grade D GVHD in the first 10 posttransplant days, when treated with this regimen. III. Determine if these patients have an acceptable incidence of life threatening grade D GHVD in the first 50 posttransplant days following this treatment regimen. IV. Determine the safety and tolerability of this treatment regimen in this patient population.

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 anti-B7.1 and anti-B7.2 antibodies for 36 hours. Patients receive total body irradiation twice daily on days -6 to -3, cyclophosphamide IV daily on days -2 and -1, and methylprednisolone IV every 12 hours for a total of 4 doses on days -2 to 0. Patients are infused with the treated donor bone marrow on day 0. Patients then receive methotrexate IV on days 1, 3, 6, and 11 and leucovorin calcium IV 24 hours after each dose of methotrexate every 6 hours for 3-8 doses each time. Patients also receive cyclosporine IV or orally twice daily on days -2 to 100. Patients are followed every 2 months for 1 year.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   up to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS: Any of the following hematologic malignancies or bone marrow failure syndromes: Acute myelogenous leukemia after induction failure, in relapse, or in second or greater complete remission (CR) Acute lymphocytic leukemia after induction failure, in relapse, in second or greater CR, or in first CR with t(9;22), t(8;14), or t(4;11) Non-Hodgkin's lymphoma (intermediate or high grade) that has failed to achieve CR with at least 2 induction regimens, in relapse, or in second or greater CR Multiple myeloma with poor prognostic features (elevated beta-2 microglobulin or high labeling index) Hodgkin's disease in relapse or that failed to achieve CR after 2 chemotherapy regimens Congenital or acquired bone marrow failure that is poorly responsive to or intolerant of current therapy Myelodysplastic syndrome of all subtypes except refractory anemia No Fanconi's anemia Patients must have a haploidentical donor and meet the following criteria: Likely to have clinical deterioration and rapid disease progression during an unrelated donor search OR Already had an unproductive donor search OR Ineligible for or has refused autologous transplant Lack an HLA A, B, DR, and DQ matched related donor (evaluated via both genotype and phenotype) Lack an HLA A, B, and DR matched unrelated donor (evaluated via both genotype and phenotype) A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma.

However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS: Age: 40 and under Performance status: ECOG 0-2 OR Lansky 50-100% for patients under 16 years Life expectancy: At least 12 weeks Hematopoietic: Blood differential count with greater than 25% blasts at time of leukapheresis Hepatic: ALT and AST no greater than 5.0 times upper limit of normal (ULN) Bilirubin no greater than 2 times ULN unless due to Gilbert's syndrome or hemolytic anemia Renal: Creatinine less than 2 times ULN Cardiovascular: Adequate cardiac function for age Pulmonary: Adequate pulmonary function for age Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception for 1 month prior to study until at least 2 months after study No active uncontrolled infection HIV negative

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior bone marrow transplant No other concurrent monoclonal antibody therapies or ex vivo T-cell depletion therapies Chemotherapy: See Disease Characteristics Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005988

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Minnesota
University of Minnesota Cancer Center
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Dana-Farber Cancer Institute
Investigators
Study Chair: Eva Guinan, MD Dana-Farber Cancer Institute
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000067977, DFCI-99205, GENE-C9909-38, NCI-G00-1801
Study First Received: July 5, 2000
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00005988     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent childhood acute lymphoblastic leukemia
recurrent adult Hodgkin lymphoma
refractory multiple myeloma
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
stage I childhood lymphoblastic lymphoma
stage II childhood lymphoblastic lymphoma
stage III childhood lymphoblastic lymphoma
stage IV childhood lymphoblastic lymphoma
recurrent childhood lymphoblastic lymphoma
recurrent childhood acute myeloid leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
childhood diffuse large cell lymphoma
childhood immunoblastic large cell lymphoma
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
stage I grade 3 follicular lymphoma
stage I adult diffuse small cleaved cell lymphoma
stage I adult diffuse mixed cell lymphoma
stage I adult diffuse large cell lymphoma
stage I adult immunoblastic large cell lymphoma
stage I adult lymphoblastic lymphoma
stage I adult Burkitt lymphoma
chronic myelomonocytic leukemia
stage III grade 3 follicular lymphoma

Study placed in the following topic categories:
Anti-Inflammatory Agents
Chronic Myelomonocytic Leukemia
Cyclosporine
Methylprednisolone
Hormone Antagonists
Miconazole
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Hormones
Cyclosporins
Follicular Lymphoma
Graft Versus Host Disease
Preleukemia
Acute Myelocytic Leukemia
Hemorrhagic Disorders
Acute Myeloid Leukemia, Adult
Neoplasm Metastasis
Methotrexate
Hodgkin Disease
Methylprednisolone Hemisuccinate
Immunoglobulins
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Antineoplastic Agents, Hormonal
Hematologic Diseases
Leukemia, Myelomonocytic, Chronic
Blood Coagulation Disorders
Leukemia, Myeloid
Glucocorticoids

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Anti-Infective Agents
Antimetabolites, Antineoplastic
Cyclosporine
Molecular Mechanisms of Pharmacological Action
Methylprednisolone
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Hormones
Cyclosporins
Preleukemia
Hemorrhagic Disorders
Pathologic Processes
Therapeutic Uses
Abortifacient Agents
Methotrexate
Cardiovascular Diseases
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors
Methylprednisolone Hemisuccinate
Immunoproliferative Disorders
Antineoplastic Agents, Hormonal
Immune System Diseases
Hematologic Diseases
Abortifacient Agents, Nonsteroidal
Glucocorticoids
Multiple Myeloma
Neoplasms
Lymphoma, Non-Hodgkin

ClinicalTrials.gov processed this record on May 07, 2009