Cyclophosphamide Plus T-Cell Transplantation for Patients With Hematologic Malignancies

NCT ID: NCT00356928

Last Updated: 2018-08-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-10-31
• Study Completion Date: 2011-05-31

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.

Conditions

Leukemia; Myelodysplastic Syndromes

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cyclophosphamide + T cells

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

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

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

Donor T cells

Intervention Type: BIOLOGICAL

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

Interventions

Cyclophosphamide

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

Intervention Type: DRUG

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

Intervention Type: BIOLOGICAL

Other Intervention Names

Cytoxan; Cy; CTX

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yvette L. Kasamon, MD

Role: STUDY_CHAIR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

R21CA121588

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA006973

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NA_00000901

Identifier Type: OTHER

Identifier Source: secondary_id

J0551

Identifier Type: -

Identifier Source: org_study_id