Back to resultsCyclophosphamide Plus T-Cell Transplantation for Patients With Hematologic Malignancies
Primary Purpose
Leukemia, Myelodysplastic Syndromes
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cyclophosphamide
Donor T cells
Sponsored by
About this trial
This is an interventional treatment trial for Leukemia focused on measuring previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, secondary acute myeloid leukemia, chronic myelomonocytic leukemia, de novo myelodysplastic syndromes
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of 1 of the following: Myelodysplastic syndromes (MDS) International Prognostic Scoring System (IPSS) score ≥ intermediate-2 Chronic myelomonocytic leukemia Acute myeloid leukemia arising from MDS Must have failed or are ineligible for or intolerant to treatment with azacitidine Patients with normal marrow cytogenetics or an isolated 5q- abnormality must have failed or are ineligible for or intolerant to treatment with lenalidomide Patients who are HLA-DR15-positive must have failed or are ineligible for pharmacologic immunosuppression (e.g., anti-thymocyte globulin, cyclosporine, steroids) No presence of cytotoxic antibodies against donor lymphocytes No HLA-identical donor available OR ineligible for HLA-identical allogeneic bone marrow transplantation HLA partially mismatched (haploidentical) related donor available First-degree related donor, including half-siblings or first cousins Inherited recombinant haplotype from parents allowed if donor shares ≥ 1 HLA antigen at each of the HLA-A, -B, and DR loci PATIENT CHARACTERISTICS: ECOG performance status (PS) 0-1 OR Karnofsky PS 80-100% Bilirubin < 3.0 mg/dL AST and ALT ≤ 4 times upper limit of normal Creatinine < 3.0 mg/dL LVEF > 35% PRIOR CONCURRENT THERAPY: See Disease Characteristics Recovered from prior therapy No prior transfusions from donor At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy No other concurrent investigational drugs
Sites / Locations
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Cyclophosphamide + T cells
Arm Description
Conditioning regimen with cyclophosphamide followed by donor T cells on Day 0.
Outcomes
Primary Outcome Measures
Maximum tolerated dose of haploidentical donor lymphocytes
Maximum dose in cells per kilogram that did not cause dose-limiting toxicity (defined as grade 3-5 non-hematologic toxicity, death within 60 days related to protocol treatment, aplasia related to treatment, or grade 3-4 graft-vs-host-disease).
Secondary Outcome Measures
Disease response
Percentage of participants who had a complete remission after protocol treatment.
Duration of response
Median length of response (in months) of participants who had a complete remission after protocol treatment.
Full Information
NCT ID
NCT00356928
First Posted
July 26, 2006
Last Updated
August 16, 2018
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00356928
Brief Title
Cyclophosphamide Plus T-Cell Transplantation for Patients With Hematologic Malignancies
Official Title
Cyclophosphamide Plus Transplantation of Partially HLA-mismatched (Haploidentical), CD8+ T Cell-depleted Peripheral Blood Cells for Patients With Myelodysplastic Syndrome, Acute Myeloid Leukemia, Lymphoma, or Myeloproliferative Disorders
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Terminated
Why Stopped
Poor accrual
Study Start Date
October 2006 (Actual)
Primary Completion Date
May 2011 (Actual)
Study Completion Date
May 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of abnormal blood cells, either by killing the cells or by stopping them from dividing. Giving cyclophosphamide together with donor lymphocytes that have been treated in the laboratory may be an effective treatment for myelodysplastic syndromes or myeloproliferative disorders.
PURPOSE: This clinical trial is studying the best dose of donor lymphocytes when given together with cyclophosphamide in treating patients with myelodysplastic syndromes or myeloproliferative disorders.
Detailed Description
OBJECTIVES:
Determine the maximum tolerated dose of allogeneic CD8-positive T-cell-depleted, haploidentical donor lymphocytes when given after cyclophosphamide in patients with myelodysplastic syndromes or myeloproliferative disorders.
OUTLINE: Patients receive cyclophosphamide on days 1 and 2. Patients then undergo infusion of allogeneic T-cell depleted donor lymphocytes on day 3.
Cohorts of patients receive escalating doses of CD8-positive T-cell-depleted haploidentical donor lymphocytes until the maximum tolerated dose is determined.
PROJECTED ACCRUAL: A total of 44 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
Leukemia, Myelodysplastic Syndromes
Keywords
previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, secondary acute myeloid leukemia, chronic myelomonocytic leukemia, de novo 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
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cyclophosphamide + T cells
Arm Type
Experimental
Arm Description
Conditioning regimen with cyclophosphamide followed by donor T cells on Day 0.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan, Cy, CTX
Intervention Description
50 mg/kg/day intravenously (IV) on Days -2 and -1.
Intervention Type
Biological
Intervention Name(s)
Donor T cells
Intervention Description
CD8-depleted T cells given IV on Day 0. Dose levels are as follows (all doses in cells/kg):
Dose level 1: 1E5 CD4+ cells and less than 3.2E3 CD8+ cells Dose level 2: 1E6 CD4+ cells and less than 3.2E4 CD8+ cells Dose level 3: 1E7 CD4+ cells and less than 3.2E5 CD8+ cells Dose level 4: 5E7 CD4+ cells and less than 1.6E6 CD8+ cells
Primary Outcome Measure Information:
Title
Maximum tolerated dose of haploidentical donor lymphocytes
Description
Maximum dose in cells per kilogram that did not cause dose-limiting toxicity (defined as grade 3-5 non-hematologic toxicity, death within 60 days related to protocol treatment, aplasia related to treatment, or grade 3-4 graft-vs-host-disease).
Time Frame
60 days
Secondary Outcome Measure Information:
Title
Disease response
Description
Percentage of participants who had a complete remission after protocol treatment.
Time Frame
Up to 6 months
Title
Duration of response
Description
Median length of response (in months) of participants who had a complete remission after protocol treatment.
Time Frame
Up to 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS:
Diagnosis of 1 of the following:
Myelodysplastic syndromes (MDS)
International Prognostic Scoring System (IPSS) score ≥ intermediate-2
Chronic myelomonocytic leukemia
Acute myeloid leukemia arising from MDS
Must have failed or are ineligible for or intolerant to treatment with azacitidine
Patients with normal marrow cytogenetics or an isolated 5q- abnormality must have failed or are ineligible for or intolerant to treatment with lenalidomide
Patients who are HLA-DR15-positive must have failed or are ineligible for pharmacologic immunosuppression (e.g., anti-thymocyte globulin, cyclosporine, steroids)
No presence of cytotoxic antibodies against donor lymphocytes
No HLA-identical donor available OR ineligible for HLA-identical allogeneic bone marrow transplantation
HLA partially mismatched (haploidentical) related donor available
First-degree related donor, including half-siblings or first cousins
Inherited recombinant haplotype from parents allowed if donor shares ≥ 1 HLA antigen at each of the HLA-A, -B, and DR loci
PATIENT CHARACTERISTICS:
ECOG performance status (PS) 0-1 OR Karnofsky PS 80-100%
Bilirubin < 3.0 mg/dL
AST and ALT ≤ 4 times upper limit of normal
Creatinine < 3.0 mg/dL
LVEF > 35%
PRIOR CONCURRENT THERAPY:
See Disease Characteristics
Recovered from prior therapy
No prior transfusions from donor
At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy
No other concurrent investigational drugs
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yvette L. Kasamon, MD
Organizational Affiliation
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Official's Role
Study Chair
Facility Information:
Facility Name
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231-2410
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Cyclophosphamide Plus T-Cell Transplantation for Patients With Hematologic Malignancies
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