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	Treatment or Intervention	Phase
Leukemia Lymphoma Multiple Myeloma	Drug: cyclophosphamide  Drug: cyclosporine  Drug: leucovorin calcium  Drug: methotrexate  Drug: methylprednisolone	Phase I

Further Study Details: 

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.

PROTOCOL 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.

Ages Eligible for Study:  up to  40 Years

Criteria

PROTOCOL ENTRY 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.]

--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

--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

Massachusetts
      Dana-Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States
Minnesota
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States

Study chairs or principal investigators

Eva Guinan,  Study Chair,  Dana-Farber/Harvard Cancer Center   

Study ID Numbers:  CDR0000067977; DFCI-99205; NCI-G00-1801; GENE-C9909-38
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  July 5, 2000
ClinicalTrials.gov Identifier:  NCT00005988
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08