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

Sponsor

Dana-Farber Cancer Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00005988

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

25.2

Actual Duration (Months)

2.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

5 participants

Allocation:

N/A

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 :

Feb 1, 2000

Actual Primary Completion Date :

Jun 16, 2001

Actual Study Completion Date :

Mar 8, 2002

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Incidence of primary graft failure [up to 30 days post-transplant]

Secondary Outcome Measures

Incidence of hyperacute GVHD [up to 100 days post-transplant]
Incidence of Grade D acute GVHD [up to 50 days post-transplant]
Incidence of adverse events [up to 100 days post-transplant]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 40 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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