Cyclophosphamide Plus T-Cell Transplantation for Patients With Hematologic Malignancies

NCT00356928 | Terminated Phase 1 DMC FDA Drug

• 4 other identifiers: J0551R21CA121588P30CA006973NA_00000901
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Leukemia; Myelodysplastic Syndromes

Keywords

previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; secondary acute myeloid leukemia; chronic myelomonocytic leukemia; de novo myelodysplastic syndromes

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Disease response

  Up to 6 months

• Duration of response

  Up to 6 months

Study Arms (1)

Cyclophosphamide + T cells

EXPERIMENTAL

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

Drug: Cyclophosphamide; Biological: Donor T cells

Interventions

Cyclophosphamide DRUG

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

Also known as: Cytoxan, Cy, CTX

Cyclophosphamide + T cells

Donor T cells 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

Cyclophosphamide + T cells

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Yvette L. Kasamon, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2006
• First Posted: July 27, 2006
• Study Start: October 1, 2006
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: August 20, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)