Phase II Maraviroc for GVHD Prevention

• Status: Completed
• Trial end date: 2018-07-12
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Successful allogeneic stem-cell transplantation is often limited by graft-versus-host disease (GVHD). Migration of donor cells into tissues plays a major role in GVHD. Drugs that block chemokine receptors such as CCR5, can potentially decrease the migration of donor cells into tissues. Blocking CCR5 after allogeneic stem-cell transplantation may therefore reduce the rates of GVHD.

PURPOSE: This study explores the efficacy of pharmacologic inhibition of CCR5 in prevention of GVHDby administering maraviroc during allogeneic stem-cell transplantation with reduced intensity conditioning.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Abramson Cancer Center of the University of Pennsylvania
• Treatments: Maraviroc

Criteria

Inclusion Criteria:

• Patients ≥18 years of age with a hematologic malignancy other than aplastic anemia or primary myelofibrosis, scheduled to undergo RIC allogeneic SCT with a peripheral blood stem cell graft from an unrelated donor, using Flu/Bu conditioning and Tac/MTX GVHD prophylaxis. The following diagnoses are included:

• Acute leukemia - AML, ALL or acute biphenotypic leukemia. Patients will have documentation of complete remission within 6 weeks prior to their transplant. Complete remission is defined as <5% blasts on a bone marrow biopsy and absence of any known extramedullary disease.

• Chronic myelogenous leukemia in any stage, but with documentation of <5% blasts on a bone marrow biopsy within 6 weeks prior to transplant.

• Myelodysplastic syndrome of any subtype, but with documentation of <5% blasts on a bone marrow biopsy within 6 weeks prior to transplant.

• Myeloproliferative disorders other than primary myelofibrosis.

• Lymphoma - All types of lymphoma are eligible.

• CLL and PLL.

• Patients who meet institutional eligibility criteria for allogeneic SCT:

• Renal function: Serum creatinine ≤2.

• Hepatic function: Baseline direct bilirubin, ALT or AST lower than three times the upper limit of normal.

• Pulmonary disease: FVC or FEV1 ≥ 40% predicted.

• Cardiac ejection fraction ≥ 40%.

• Availability of an unrelated donor, identified and screened by the NMDP. The donor will have at least 7/8 HLA-A, -B, -C and -DRB1 matching by high resolution molecular typing and will meet NMDP eligibility criteria to serve as a peripheral blood stem-cell donor.

• Karnofsky score ≥ 70% at the time of screening.

• Capacity to understand and sign the study informed consent form.

• Negative pregnancy test. Women of childbearing potential (not having had a hysterectomy, a bilateral oophorectomy or bilateral tubal ligation, or be post-menopausal with a total cessation of menses of > 1 year) must agree to use documented reliable method(s) of contraception. Men should agree to use condoms during the study period.

• Co-enrollment in other clinical trials that do not include experimental GVHD therapies is allowed.

Exclusion Criteria

• Patients with aplastic anemia or primary myelofibrosis. Patients with marrow fibrosis secondary to MDS, AML or a myeloproliferative disorder other than primary myelofibrosis are eligible.

• Patients who are not expected to be available for follow-up in our institution for at least 180 days after the transplant.

• Prior allogeneic SCT.

• Uncontrolled bacterial, viral or fungal infections.

• Patients who receive maraviroc for the treatment of HIV infection.

• Patients receiving other investigational drugs for GVHD.

• Co-enrollment in other clinical trials that do not include experimental GVHD therapies is allowed.

• Patients with prior malignancies are excluded unless treated with curative intent and known to be free of disease for at least 2 years.