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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00005988
• Other study ID #: 99-205
• Secondary ID: P30CA006516GENE-
• Status: Completed
• Phase: Phase 1
• First received: July 5, 2000
• Last updated: March 30, 2017
• Start date: February 2000
• Est. completion date: March 8, 2002

Study information

• Verified date: March 2017
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: March 8, 2002
• Est. primary completion date: June 16, 2001
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease
• Leukemia
• Lymphoma
• Myelodysplastic Syndromes
• Myeloma
• Preleukemia
• Syndrome

Intervention

Drug:
• cyclophosphamide

• cyclosporine

• leucovorin calcium

• methotrexate

• methylprednisolone

Procedure:
• in vitro-treated bone marrow transplantation

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of primary graft failure		up to 30 days post-transplant
Secondary	Incidence of hyperacute GVHD		up to 100 days post-transplant
Secondary	Incidence of Grade D acute GVHD		up to 50 days post-transplant
Secondary	Incidence of adverse events		up to 100 days post-transplant