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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

Primary Purpose

Graft Versus Host Disease, Leukemia, Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
cyclophosphamide
cyclosporine
leucovorin calcium
methotrexate
methylprednisolone
in vitro-treated bone marrow transplantation
radiation therapy
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Graft Versus Host Disease focused on measuring recurrent childhood acute lymphoblastic leukemia, recurrent adult Hodgkin lymphoma, refractory multiple myeloma, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, stage I childhood lymphoblastic lymphoma, stage II childhood lymphoblastic lymphoma, stage III childhood lymphoblastic lymphoma, stage IV childhood lymphoblastic lymphoma, recurrent childhood lymphoblastic lymphoma, recurrent childhood acute myeloid leukemia, recurrent adult acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, childhood diffuse large cell lymphoma, childhood immunoblastic large cell lymphoma, adult acute myeloid leukemia in remission, adult acute lymphoblastic leukemia in remission, childhood acute myeloid leukemia in remission, childhood acute lymphoblastic leukemia in remission, recurrent/refractory childhood Hodgkin lymphoma, stage I grade 3 follicular lymphoma, stage I adult diffuse small cleaved cell lymphoma, stage I adult diffuse mixed cell lymphoma, stage I adult diffuse large cell lymphoma, stage I adult immunoblastic large cell lymphoma, stage I adult lymphoblastic lymphoma, stage I adult Burkitt lymphoma, chronic myelomonocytic leukemia, stage III grade 3 follicular lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage III adult diffuse large cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, stage III adult Burkitt lymphoma, stage IV grade 3 follicular lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, stage IV adult Burkitt lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult Burkitt lymphoma, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, graft versus host disease, stage I childhood small noncleaved cell lymphoma, stage I childhood large cell lymphoma, stage II childhood small noncleaved cell lymphoma, stage II childhood large cell lymphoma, stage III childhood small noncleaved cell lymphoma, stage III childhood large cell lymphoma, stage IV childhood small noncleaved cell lymphoma, stage IV childhood large cell lymphoma, recurrent childhood small noncleaved cell lymphoma, recurrent childhood large cell lymphoma, contiguous stage II grade 3 follicular lymphoma, contiguous stage II adult diffuse small cleaved cell lymphoma, contiguous stage II adult diffuse mixed cell lymphoma, contiguous stage II adult immunoblastic large cell lymphoma, contiguous stage II adult diffuse large cell lymphoma, contiguous stage II adult Burkitt lymphoma, contiguous stage II adult lymphoblastic lymphoma, noncontiguous stage II grade 3 follicular lymphoma, noncontiguous stage II adult diffuse small cleaved cell lymphoma, noncontiguous stage II adult diffuse mixed cell lymphoma, noncontiguous stage II adult immunoblastic large cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult Burkitt lymphoma, noncontiguous stage II adult lymphoblastic lymphoma, refractory cytopenia with multilineage dysplasia, childhood myelodysplastic syndromes

Eligibility Criteria

undefined - 40 Years (Child, Adult)All SexesDoes not accept 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

Sites / Locations

  • Dana-Farber Cancer Institute
  • University of Minnesota Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

in vitro-treated bone marrow transplantation

Arm Description

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,

Outcomes

Primary Outcome Measures

Incidence of primary graft failure

Secondary Outcome Measures

Incidence of hyperacute GVHD
Incidence of Grade D acute GVHD
Incidence of adverse events

Full Information

First Posted
July 5, 2000
Last Updated
March 30, 2017
Sponsor
Dana-Farber Cancer Institute
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00005988
Brief Title
Bone Marrow Transplantation With Specially Treated Bone Marrow in Treating Patients With Hematologic Cancer That Have Not Responded to Previous Therapy
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
February 2000 (Actual)
Primary Completion Date
June 16, 2001 (Actual)
Study Completion Date
March 8, 2002 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft Versus Host Disease, Leukemia, Lymphoma, Myelodysplastic Syndromes, Myeloma
Keywords
recurrent childhood acute lymphoblastic leukemia, recurrent adult Hodgkin lymphoma, refractory multiple myeloma, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, stage I childhood lymphoblastic lymphoma, stage II childhood lymphoblastic lymphoma, stage III childhood lymphoblastic lymphoma, stage IV childhood lymphoblastic lymphoma, recurrent childhood lymphoblastic lymphoma, recurrent childhood acute myeloid leukemia, recurrent adult acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, childhood diffuse large cell lymphoma, childhood immunoblastic large cell lymphoma, adult acute myeloid leukemia in remission, adult acute lymphoblastic leukemia in remission, childhood acute myeloid leukemia in remission, childhood acute lymphoblastic leukemia in remission, recurrent/refractory childhood Hodgkin lymphoma, stage I grade 3 follicular lymphoma, stage I adult diffuse small cleaved cell lymphoma, stage I adult diffuse mixed cell lymphoma, stage I adult diffuse large cell lymphoma, stage I adult immunoblastic large cell lymphoma, stage I adult lymphoblastic lymphoma, stage I adult Burkitt lymphoma, chronic myelomonocytic leukemia, stage III grade 3 follicular lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage III adult diffuse large cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, stage III adult Burkitt lymphoma, stage IV grade 3 follicular lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, stage IV adult Burkitt lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult Burkitt lymphoma, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, graft versus host disease, stage I childhood small noncleaved cell lymphoma, stage I childhood large cell lymphoma, stage II childhood small noncleaved cell lymphoma, stage II childhood large cell lymphoma, stage III childhood small noncleaved cell lymphoma, stage III childhood large cell lymphoma, stage IV childhood small noncleaved cell lymphoma, stage IV childhood large cell lymphoma, recurrent childhood small noncleaved cell lymphoma, recurrent childhood large cell lymphoma, contiguous stage II grade 3 follicular lymphoma, contiguous stage II adult diffuse small cleaved cell lymphoma, contiguous stage II adult diffuse mixed cell lymphoma, contiguous stage II adult immunoblastic large cell lymphoma, contiguous stage II adult diffuse large cell lymphoma, contiguous stage II adult Burkitt lymphoma, contiguous stage II adult lymphoblastic lymphoma, noncontiguous stage II grade 3 follicular lymphoma, noncontiguous stage II adult diffuse small cleaved cell lymphoma, noncontiguous stage II adult diffuse mixed cell lymphoma, noncontiguous stage II adult immunoblastic large cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult Burkitt lymphoma, noncontiguous stage II adult lymphoblastic lymphoma, refractory cytopenia with multilineage dysplasia, childhood myelodysplastic syndromes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
in vitro-treated bone marrow transplantation
Arm Type
Experimental
Arm Description
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,
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
cyclosporine
Intervention Type
Drug
Intervention Name(s)
leucovorin calcium
Intervention Type
Drug
Intervention Name(s)
methotrexate
Intervention Type
Drug
Intervention Name(s)
methylprednisolone
Intervention Type
Procedure
Intervention Name(s)
in vitro-treated bone marrow transplantation
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Primary Outcome Measure Information:
Title
Incidence of primary graft failure
Time Frame
up to 30 days post-transplant
Secondary Outcome Measure Information:
Title
Incidence of hyperacute GVHD
Time Frame
up to 100 days post-transplant
Title
Incidence of Grade D acute GVHD
Time Frame
up to 50 days post-transplant
Title
Incidence of adverse events
Time Frame
up to 100 days post-transplant

10. Eligibility

Sex
All
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eva Guinan, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Minnesota Cancer Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
18617635
Citation
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.
Results Reference
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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

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