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Phase II Maraviroc for GVHD Prevention

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ClinicalTrials.gov Identifier: NCT01785810
Recruitment Status : Completed
First Posted : February 7, 2013
Results First Posted : January 11, 2021
Last Update Posted : January 11, 2021
Sponsor:
Information provided by (Responsible Party):
Abramson Cancer Center of the University of Pennsylvania

Tracking Information
First Submitted Date  ICMJE February 5, 2013
First Posted Date  ICMJE February 7, 2013
Results First Submitted Date  ICMJE September 24, 2020
Results First Posted Date  ICMJE January 11, 2021
Last Update Posted Date January 11, 2021
Actual Study Start Date  ICMJE February 2013
Actual Primary Completion Date November 11, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 16, 2020)
Day +180 Rate of Grade II-IV Acute GVHD [ Time Frame: 180 days ]
The cumulative incidence of grade II-IV acute GVHD by day 180 after the stem-cell infusion. This is based on consensus conference criteria.
Original Primary Outcome Measures  ICMJE
 (submitted: February 6, 2013)
Number of Serious Adverse Events [ Time Frame: 180 days ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase II Maraviroc for GVHD Prevention
Official Title  ICMJE A Phase II Study to Assess the Efficacy of Maraviroc in Prophylaxis of GVHD in Patients With Hematologic Malignancies Undergoing Reduced-Intensity Allogeneic SCT From Unrelated Donors
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.

Detailed Description

Detailed Description:

PRIMARY OBJECTIVES:

To estimate the cumulative incidence of grade 2-4 acute GVHD by day 180 with the addition of maraviroc to a standard prophylaxis regimen in patients with hematologic malignancies undergoing reduced intensity allogeneic stem-cell transplantation (RIC SCT) from unrelated donors.

SECONDARY OBJECTIVES:

  1. To assess the toxicity of a prolonged administration of maraviroc in patients undergoing RIC SCT.
  2. To estimate the rates of severe (grade 3-4) acute GVHD by day 100 and 180, grade 2-4 acute GVHD by day 100, organ-specific acute GVHD, chronic GVHD, relapse, infections, non-relapse mortality, use of immunosuppressive therapies and 1-year survival in patients treated with maraviroc after RIC SCT.
  3. To assess the effect of treatment with maraviroc on immune recovery, engraftment and donor T-cell chimerism in peripheral blood and in target organs.
  4. To assess the effect of donor and recipient CCR5 genotype on the incidence of acute GVHD in patients receiving maraviroc as part of a GVHD prophylaxis regimen.

OUTLINE: Patients 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 receive maraviroc from day -3 to d+ 90.

Patients are followed for 1 year after the stem-cell infusion.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hematologic Malignancy
Intervention  ICMJE Drug: Maraviroc 300 mg
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.
Other Name: CCR5 Antagonist
Study Arms  ICMJE Experimental: Maraviroc
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.
Intervention: Drug: Maraviroc 300 mg
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 6, 2013)
37
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 12, 2018
Actual Primary Completion Date November 11, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01785810
Other Study ID Numbers  ICMJE UPCC 04712
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Abramson Cancer Center of the University of Pennsylvania
Study Sponsor  ICMJE Abramson Cancer Center of the University of Pennsylvania
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: David Porter, MD Abramson Cancer Center of the University of Pennsylvania
PRS Account Abramson Cancer Center of the University of Pennsylvania
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP