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Bone Marrow Transplantation With Specially Treated Bone Marrow in Treating Patients With Hematologic Cancer That Have Not Responded to Previous Therapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00005988
Recruitment Status : Completed
First Posted : May 3, 2004
Last Update Posted : April 4, 2017
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eva C. Guinan, MD, Dana-Farber Cancer Institute

Brief Summary:

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 or disease Intervention/treatment Phase
Graft Versus Host Disease Leukemia Lymphoma Myelodysplastic Syndromes Myeloma Drug: cyclophosphamide Drug: cyclosporine Drug: leucovorin calcium Drug: methotrexate Drug: methylprednisolone Procedure: in vitro-treated bone marrow transplantation Radiation: radiation therapy Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 2000
Actual Primary Completion Date : June 16, 2001
Actual Study Completion Date : March 8, 2002

Arm Intervention/treatment
Experimental: in vitro-treated bone marrow transplantation
  • Donor bone marrow will be harvested on Day -2
  • Bone Marrow incubated with irradiated recipient cells and anti-B7.1 and anti-B7.2 for 36 hours.
  • Bone marrow will be infused intravenously
  • Cyclophosphamide will be administered IV once daily
  • Total Body Irradiation (TBI) will be delivered per institutional practice
  • Methylprednisolone will be administered IV as 4 doses separated by 12 hours,
Drug: cyclophosphamide
Drug: cyclosporine
Drug: leucovorin calcium
Drug: methotrexate
Drug: methylprednisolone
Procedure: in vitro-treated bone marrow transplantation
Radiation: radiation therapy

Primary Outcome Measures :
  1. Incidence of primary graft failure [ Time Frame: up to 30 days post-transplant ]

Secondary Outcome Measures :
  1. Incidence of hyperacute GVHD [ Time Frame: up to 100 days post-transplant ]
  2. Incidence of Grade D acute GVHD [ Time Frame: up to 50 days post-transplant ]
  3. Incidence of adverse events [ Time Frame: up to 100 days post-transplant ]

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 40 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age ≤40 years.
  • Diagnoses—patients with the following hematologic malignancies and bone marrow failure syndromes:

    • Acute myelogenous leukemia—induction failure, relapse, second or greater complete remission (CR)
    • Acute lymphocytic leukemia—induction failure, relapse, second or greater CR, first CR with t(9;22), t(8;14), or t(4;11)
    • Non-Hodgkin's lymphoma (intermediate or high grade) which has failed to achieve CR with at least two induction regimens, relapse, second or greater CR
    • Multiple myeloma with poor prognostic features (elevated 0-2 microglobulin or high labeling index)
    • Hodgkin's disease in relapse or which fails to achieve CR after two chemotherapy regimens
    • Congenital or acquired bone marrow failure - poorly responsive to or intolerant of current therapy
    • Myelodysplastic syndrome of all subtypes except refractory anemia (RA)
  • Patient has a haploidentical family member that meets medical criteria for donation.
  • Eligibility for other transplant types:

    • Patient considered likely to have clinical deterioration and rapid disease progression during an unrelated donor search, or
    • Patient who has already had an unproductive donor search or
    • Patient ineligible for or has refused autologous transplant
  • Adequate renal and hepatic function for age:

    • Serum creatinine <2 x ULN
    • Alanine aminotransferase (ALT, SGPT) x ULN
    • Aspartate aminotransferase (AST, SGOT) x ULN
    • Total bilirubin 5_2 x ULN except if bilirubin is elevated due to Gilbert's syndrome or hemolytic anemia
  • Adequate cardiac and pulmonary function for age.
  • ECOG Performance Status 0, 1, or 2 or Lansky performance scale >50% for patients <16 years of age.
  • Voluntary witnessed written informed consent. Children will be asked for assent where appropriate.
  • The patient, if female, must be post-menopausal, premenarcheal, or sterile, or if the patient is of childbearing potential, she must be practicing a method of birth control considered effective and medically acceptable by the investigator for a minimum of 1 month prior to study entry and at least 2 months after the study end.
  • Patient must have undergone successful leukapheresis to obtain adequate antigen presenting cells.
  • Any patient who enters the study in a relapse state, with evidence of end organ (pulmonary, renal, or hepatic) toxicity, or with recent recovery from infection, who may potentially have little benefit from this protocol, must have his/her eligibility status discussed with the Principal Investigator.
  • Patient must have life expectancy of at least 12 weeks.

Exclusion Criteria

  • Eligibility for other transplant types:

    • Patient has family donor who is matched or single antigen mismatched at HLA-A, HLA-B, HLA-DR, and HLA-DQ. Donorrecipient matching must be evaluated via both phenotype and genotype.
    • Patient has available unrelated donor who is matched at HLA-A, HLA-B, and HLA-DR. Donor-recipient matching must be evaluated via both phenotype and genotype.
  • Active uncontrolled infection (continued positive blood or soft tissue cultures despite appropriate antibiotic treatment)
  • Positive 13-HCG in a female of childbearing potential
  • Evidence of HIV infection or known HIV positive serology
  • Any prior bone marrow transplant
  • A peripheral blood differential count at the time of leukapheresis with greater than 25% blasts. This exclusion criterion is valid only for the first four patients enrolled.
  • Patients with Fanconi's anemia

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00005988

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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
National Cancer Institute (NCI)
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Study Chair: Eva Guinan, MD Dana-Farber Cancer Institute

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Responsible Party: Eva C. Guinan, MD, Principal Investigator, Dana-Farber Cancer Institute Identifier: NCT00005988     History of Changes
Other Study ID Numbers: 99-205
P30CA006516 ( U.S. NIH Grant/Contract )
CDR0000067977 ( Other Identifier: other )
First Posted: May 3, 2004    Key Record Dates
Last Update Posted: April 4, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eva C. Guinan, MD, Dana-Farber Cancer Institute:
recurrent adult acute lymphoblastic leukemia
adult acute lymphoblastic leukemia in remission
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
childhood diffuse large cell lymphoma
childhood immunoblastic large cell lymphoma
adult acute myeloid 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
Additional relevant MeSH terms:
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Antineoplastic Agents, Hormonal
Myelodysplastic Syndromes
Graft vs Host Disease
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Pathologic Processes
Hematologic Diseases
Bone Marrow Diseases
Precancerous Conditions
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents