Phase II Maraviroc for GVHD Prevention

NCT01785810 | Completed Phase 2 Results DMC

• 1 other identifier: UPCC 04712
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hematologic Malignancy

Outcome Measures

Primary Outcomes (1)

• Day +180 Rate of Grade II-IV Acute GVHD

  The cumulative incidence of grade II-IV acute GVHD by day 180 after the stem-cell infusion. This is based on consensus conference criteria.

  180 days

Study Arms (1)

Maraviroc

EXPERIMENTAL

Phase II, single arm, single center trial, assessing the efficacy of the combination of tacrolimus, methotrexate and maraviroc as graft-versus-host disease (GVHD) prophylaxis after unrelated donor peripheral blood stem-cell transplantation in patients with hematologic malignancies. Patients enrolled on this trial will receive a standard conditioning regimen with fludarabine and busulfan followed by a peripheral blood stem cell infusion from an unrelated donor, standard GVHD prophylaxis and standard antiviral and antifungal prophylaxis. In addition, all patients will receive maraviroc from day -3 to d+ 90.

Drug: Maraviroc 300 mg

Interventions

Maraviroc 300 mg DRUG

Patients enrolled on this trial will receive a standard conditioning regimen with fludarabine and busulfan followed by a peripheral blood stem cell infusion from an unrelated donor, standard GVHD prophylaxis and standard antiviral and antifungal prophylaxis. In addition, all patients will receive maraviroc from day -3 to d+ 90.

Also known as: CCR5 Antagonist

Maraviroc

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

Maraviroc

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Michael Gardo
• Organization: Abramson Cancer Center

michael.gardo@uphs.upenn.edu

215-615-2232

Study Officials

• David Porter, MD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2013
• First Posted: February 7, 2013
• Study Start: February 1, 2013
• Primary Completion: November 11, 2016
• Study Completion: July 12, 2018
• Last Updated: January 11, 2021
• Results First Posted: January 11, 2021

Record last verified: 2020-12

Locations

US (1)