Maraviroc in Patients Undergoing Non-Myeloablative Allogeneic Stem-Cell Transplantation

• Maraviroc 150 MG (Drug), also known as CCR5 Blockade: Maraviroc b.i.d. (in addition to the standard prophylaxis therapy of tacrolimus and methotrexate) beginning after last dose of chemotherapy conditioning regimen until day 30 after stem-cell infusion.
• Maraviroc 300 mg (Drug), also known as CCR5 Blockade: Maraviroc b.i.d. (in addition to the standard prophylaxis therapy of tacrolimus and methotrexate) beginning after last dose of chemotherapy conditioning regimen until day 30 after stem-cell infusion.
• Maraviroc 300 mg Phase II (Drug), also known as CCR5 Blockade: Maraviroc b.i.d. (in addition to the standard prophylaxis therapy of tacrolimus and methotrexate) beginning after last dose of chemotherapy conditioning regimen until day 30 after stem-cell infusion.

Primary outcomes

• Safety of Maraviroc [1 year]: number of Adverse Events following exposure to Maraviroc
• Efficacy of Maraviroc [8 weeks]: Efficacy is measured by number of participants progressing to acute GVHD. If acute GVHD is noted in a participant following exposure to study drug, then efficacy was not achieved. If no GVHD was noted following exposure, then efficacy was achieved in that participant

Secondary outcomes

• Pharmacokinetic Profile of Maraviroc in Patients Undergoing Nonmyeloablative Allogeneic SCT [pre-dose, 1,2,3,4,6,12 hours post-dose]: Plasma maraviroc levels were measured in the blood with a target level of 100 ng per milliliter. Blood was drawn on Day 0 and Day 10-12 at pre-dose, 1, 2, 3, 4, 6, and 12 hours post-dose. Data was analyzed looking at the number of patients to achieve the target of 100 ng per milliliter at any time point.
• Number of Patients Treated With Maraviroc During SCT That Develop Chronic GVHD [1 year]: count of how many patients treated with Maraviroc during SCT go on to develop chronic GVHD in 1 year
• Rate of Early Mortality After Transplant [1 year]: Number of participants who died without relapse within 1 year of SCT
• Number of Participants Who Relapsed During Study Period [1 year and 11 months]: Number of participants who received Maraviroc during SCT who relapsed within 1 year and 11 months. This was based on a diagnosis made by their physician that their primary cancer had returned.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* patients scheduled to undergo non-myeloablative allogeneic stem-cell transplantation.
* meet institutional eligibility criteria for allogeneic SCT. Significant criteria are:

  * Renal function: Serum creatinine <2; or calculated creatinine clearance > 40 mL/min/1.72m2;
  * 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%.

Exclusion Criteria:

* Patients not expected to be available for follow-up in our institution for at least 100 days after the transplant
* Patients who are not undergoing standard non-myeloablative SCT with Flu/Bu conditioning and Tax/MTX GVHD prophylaxis
* Patients with uncontrolled bacterial, viral or fungal infections
* Patients who take strong inducers or inhibitors of the CYP450A4
* Patients receiving other investigational drugs for GVHD
* Women who are pregnant, plan to become pregnant or are breastfeeding

Participant flow

Outcome results

• Safety of Maraviroc (Primary), Number, Number of AEs: Phase 1: 150mg Maraviroc 8; Phase 1: 300mg Maraviroc 6; Phase 2: 300mg Maraviroc 18
• Efficacy of Maraviroc (Primary), Number, Participants: Phase 1: 150mg Maraviroc 0; Phase 1: 300mg Maraviroc 0; Phase 2: 300mg Maraviroc 0
• Pharmacokinetic Profile of Maraviroc in Patients Undergoing Nonmyeloablative Allogeneic SCT (Secondary), Number, number of patients to reach target: Phase 1: 150mg Maraviroc 4; Phase 1: 300mg Maraviroc 6; Phase 2: 300mg Maraviroc 0
• Number of Patients Treated With Maraviroc During SCT That Develop Chronic GVHD (Secondary), Count of participants, Participants: Phase 1: 150mg Maraviroc 1; Phase 1: 300mg Maraviroc 3; Phase 2: 300mg Maraviroc 2
• Rate of Early Mortality After Transplant (Secondary), Count of participants, Participants: Phase 1: 150mg Maraviroc 2; Phase 1: 300mg Maraviroc 0; Phase 2: 300mg Maraviroc 4
• Number of Participants Who Relapsed During Study Period (Secondary), Count of participants, Participants: Phase 1: 150mg Maraviroc 2; Phase 1: 300mg Maraviroc 2; Phase 2: 300mg Maraviroc 15

Adverse events

Other adverse events by term

• Results publication: Reshef R, Luger SM, Hexner EO, Loren AW, Frey NV, Nasta SD, Goldstein SC, Stadtmauer EA, Smith J, Bailey S, Mick R, Heitjan DF, Emerson SG, Hoxie JA, Vonderheide RH, Porter DL. Blockade of lymphocyte chemotaxis in visceral graft-versus-host disease. N Engl J Med. 2012 Jul 12;367(2):135-45. doi: 10.1056/NEJMoa1201248. PMID 22784116

• David Porter, MD, Principal investigator, University of Pennsylvania