Cyclophosphamide Plus T-Cell Transplantation for Patients With Hematologic Malignancies

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Terminated

CT.gov ID

NCT00356928

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

Actual Duration (Months)

0.3

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Myelodysplastic Syndromes	Drug: Cyclophosphamide Biological: Donor T cells	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

14 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 1, 2006

Actual Primary Completion Date :

May 1, 2011

Actual Study Completion Date :

May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cyclophosphamide + T cells Conditioning regimen with cyclophosphamide followed by donor T cells on Day 0.	Drug: Cyclophosphamide 50 mg/kg/day intravenously (IV) on Days -2 and -1. Other Names: Cytoxan Cy CTX Biological: Donor T cells 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

Arm

Intervention/Treatment

Experimental: Cyclophosphamide + T cells

Conditioning regimen with cyclophosphamide followed by donor T cells on Day 0.

Drug: Cyclophosphamide

50 mg/kg/day intravenously (IV) on Days -2 and -1.

Other Names:

Cytoxan

CTX

Biological: Donor T cells

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

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose of haploidentical donor lymphocytes [60 days]
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 [Up to 6 months]
Percentage of participants who had a complete remission after protocol treatment.
Duration of response [Up to 6 months]
Median length of response (in months) of participants who had a complete remission after protocol treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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