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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

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eva C. Guinan, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00005988
First received: July 5, 2000
Last updated: March 30, 2017
Last verified: March 2017
July 5, 2000
March 30, 2017
February 2000
June 16, 2001   (Final data collection date for primary outcome measure)
Incidence of primary graft failure [ Time Frame: up to 30 days post-transplant ]
Not Provided
Complete list of historical versions of study NCT00005988 on ClinicalTrials.gov Archive Site
  • Incidence of hyperacute GVHD [ Time Frame: up to 100 days post-transplant ]
  • Incidence of Grade D acute GVHD [ Time Frame: up to 50 days post-transplant ]
  • Incidence of adverse events [ Time Frame: up to 100 days post-transplant ]
Not Provided
Not Provided
Not Provided
 
Bone Marrow Transplantation With Specially Treated Bone Marrow in Treating Patients With Hematologic Cancer That Have Not Responded to Previous Therapy
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

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.

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.

Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • 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
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,
Interventions:
  • Drug: cyclophosphamide
  • Drug: cyclosporine
  • Drug: leucovorin calcium
  • Drug: methotrexate
  • Drug: methylprednisolone
  • Procedure: in vitro-treated bone marrow transplantation
  • Radiation: radiation therapy
Davies JK, Gribben JG, Brennan LL, Yuk D, Nadler LM, Guinan EC. Outcome of alloanergized haploidentical bone marrow transplantation after ex vivo costimulatory blockade: results of 2 phase 1 studies. Blood. 2008 Sep 15;112(6):2232-41. doi: 10.1182/blood-2008-03-143636. Epub 2008 Jul 10.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
5
March 8, 2002
June 16, 2001   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
up to 40 Years   (Child, Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00005988
99-205
P30CA006516 ( U.S. NIH Grant/Contract )
GENE-C9909-38
NCI-G00-1801
CDR0000067977 ( Other Identifier: other )
Yes
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: No
Eva C. Guinan, MD, Dana-Farber Cancer Institute
Dana-Farber Cancer Institute
National Cancer Institute (NCI)
Study Chair: Eva Guinan, MD Dana-Farber Cancer Institute
Dana-Farber Cancer Institute
March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP