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Combination Chemotherapy and Antithymocyte Globulin in Reducing Graft-Versus-Host Disease in Patients Undergoing Donor Stem Cell Transplantation For Myelodysplastic Syndrome or Myeloproliferative Disorder

Information source: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Chronic Myeloproliferative Disorders; Graft Versus Host Disease; Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases

Intervention: anti-thymocyte globulin (Biological); busulfan (Drug); cyclophosphamide (Drug); cyclosporine (Drug); methotrexate (Drug); allogeneic bone marrow transplantation (Procedure); peripheral blood stem cell transplantation (Procedure)

Phase: Phase 1/Phase 2

Status: Completed

Sponsored by: Fred Hutchinson Cancer Research Center

Official(s) and/or principal investigator(s):
H. Joachim Deeg, MD, Study Chair, Affiliation: Fred Hutchinson Cancer Research Center

Summary

RATIONALE: Combining antithymocyte globulin with combination chemotherapy before donor peripheral stem cell transplantation may reduce the chance of developing graft-versus-host disease following transplantation. PURPOSE: Phase I/II trial to study the effectiveness of combining antithymocyte globulin with busulfan and cyclophosphamide in reducing graft-versus-host disease in patients who are undergoing donor stem cell transplantation for myelodysplastic syndrome or other myeloproliferative disorder.

Clinical Details

Official title: Conditioning With Targeted Busulfan, Cyclophosphamide and Thymoglobulin for Allogeneic Marrow or Peripheral Blood Stem Cell (PBSC) Transplantation for Myelodysplasia and Myeloproliferative Disorders

Study design: Masking: Open Label, Primary Purpose: Supportive Care

Detailed description: OBJECTIVES:

- Determine the incidence of acute graft-vs-host disease (GVHD) requiring therapy in

patients with myelodysplastic syndromes or myeloproliferative disorders treated with busulfan, cyclophosphamide, and anti-thymocyte globulin prior to transplantation with filgrastim (G-CSF)-mobilized peripheral blood stem cells (or bone marrow) from related or unrelated donors.

- Determine the incidence of relapse and relapse-free survival in patients treated with

this regimen.

- Determine the incidence of non-relapse mortality by day 100 and 1 year

posttransplantation in patients treated with this regimen.

- Determine the incidence of Epstein-Barr virus reactivation, infections, and chronic

GVHD in patients treated with this regimen. OUTLINE: This is a dose-escalation study of anti-thymocyte globulin.

- Conditioning and graft-vs-host disease (GVHD) prophylaxis: Patients receive oral

busulfan every 6 hours on days - 7 to -4 (16 doses), cyclophosphamide IV on days -3 and

- 2, and anti-thymocyte globulin IV over 3 hours on days -3, -2, and -1.

Cohorts of 15 patients receive adjusted doses of anti-thymocyte globulin to determine the optimal dose at which Epstein-Barr virus (EBV) activation and GVHD are reduced. The optimal dose is the dose at which 2 consecutive cohorts receive the same regimen.

- Stem cell transplantation: Patients undergo peripheral blood stem cell (PBSC) or bone

marrow transplantation on day 0.

- Posttransplantation GVHD prophylaxis: Patients receive cyclosporine IV continuously on

days - 1 to 4 and then orally twice daily until day 180. Patients also receive

methotrexate on days 1, 3, 6, and 11. Patients are followed every 6 months for 2 years and then annually thereafter. PROJECTED ACCRUAL: A total of 30-45 patients will be accrued for this study within 2 years.

Eligibility

Minimum age: N/A. Maximum age: 65 Years. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

- Diagnosis of 1 of the following:

- Myelodysplastic syndromes (including those that have evolved to acute myeloid

leukemia)

- Myeloproliferative disorders

- No chronic myelogenous leukemia

- Other diseases eligible for conditioning with targeted busulfan,

cyclophosphamide, and anti-thymocyte globulin that are not candidates for other studies

- Available related or unrelated donor compatible for HLA-A, -B, -C, DRB1, and DQB1

- A single allele mismatch at HLA-A, -B, -C, or DRB1 is allowed

PATIENT CHARACTERISTICS: Age

- 65 and under

Performance status

- Not specified

Life expectancy

- No severe limitation due to other diseases

Hematopoietic

- Not specified

Hepatic

- AST no greater than 2 times normal

- No hepatic disease

Renal

- Creatinine no greater than 2 times upper limit of normal OR

- Creatinine clearance at least 50% for age, gender, and weight

Cardiovascular

- No cardiac insufficiency requiring treatment

- No symptomatic coronary artery disease

Pulmonary

- No severe or mild hypoxemia

- pO_2 at least 70 mm Hg and DLCO at least 70% of predicted OR

- pO_2 at least 80 mm Hg and DLCO at least 60% of predicted

Other

- Not pregnant or nursing

- Fertile patients must use effective contraception

- HIV negative

PRIOR CONCURRENT THERAPY: Biologic therapy

- No growth factors given posttransplantation concurrently with methotrexate

immunosuppression Chemotherapy

- Not specified

Endocrine therapy

- Not specified

Radiotherapy

- Not specified

Surgery

- Not specified

Locations and Contacts

Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, United States
Additional Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: October 2002
Last updated: May 12, 2010

Page last updated: August 20, 2015

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