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

March 30, 2017 updated by: Eva C. Guinan, MD, Dana-Farber Cancer Institute

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

5

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 40 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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: leucovorin calcium
Radiation: radiation therapy
Drug: methotrexate
Drug: methylprednisolone
Drug: cyclosporine
Procedure: in vitro-treated bone marrow transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of primary graft failure
Time Frame: up to 30 days post-transplant
up to 30 days post-transplant

Secondary Outcome Measures

Outcome Measure
Time Frame
Incidence of hyperacute GVHD
Time Frame: up to 100 days post-transplant
up to 100 days post-transplant
Incidence of Grade D acute GVHD
Time Frame: up to 50 days post-transplant
up to 50 days post-transplant
Incidence of adverse events
Time Frame: up to 100 days post-transplant
up to 100 days post-transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dana-Farber Cancer Institute

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Eva Guinan, MD, Dana-Farber Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2000

Primary Completion (Actual)

June 16, 2001

Study Completion (Actual)

March 8, 2002

Study Registration Dates

First Submitted

July 5, 2000

First Submitted That Met QC Criteria

April 30, 2004

First Posted (Estimate)

May 3, 2004

Study Record Updates

Last Update Posted (Actual)

April 4, 2017

Last Update Submitted That Met QC Criteria

March 30, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 99-205
  • P30CA006516 (U.S. NIH Grant/Contract)
  • GENE-C9909-38
  • NCI-G00-1801
  • CDR0000067977 (Other Identifier: other)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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