Cyclophosphamide Plus T-Cell Transplantation for Patients With Hematologic Malignancies

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00356928
• Other study ID #: J0551
• Secondary ID: R21CA121588P30CA
• Status: Terminated
• Phase: Phase 1
• Start date: October 2006
• Est. completion date: May 2011

Study information

• Verified date: August 2018
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Myelodysplastic Syndromes
• Myeloproliferative Disorders
• Preleukemia
• Syndrome

Intervention

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

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

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	60 days
Secondary	Disease response	Percentage of participants who had a complete remission after protocol treatment.	Up to 6 months
Secondary	Duration of response	Median length of response (in months) of participants who had a complete remission after protocol treatment.	Up to 6 months