Clinical Trial 24380

• Overview

  Study Title:

  A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase III Trial of remestemcel-L-rknd added to ruxolitinib for Grade III-IV Steroid-Refractory Acute Graft-Versus-Host Disease

  Summary:

  This study is a randomized, double-blind, placebo-controlled, multicenter Phase III trial to compare the efficacy and safety of remestemcel-L-rknd (remestemcel-L), ex-vivo cultured adult human mesenchymal stromal cells (MSC), combined with ruxolitinib vs. ruxolitinib combined with placebo as second-line therapy in adult patients with Grade III-IV steroid-refractory acute graft-versus-host disease (SR-aGVHD).

  Objective:

  Primary objective: to compare the ORR between the 2 arms, where a response is defined as a PR or CR on Day 28 post-randomization without new intervening systemic therapy. Secondary objective: 1. Overall survival (OS) through day 180 post-randomization. 2. Duration of response (DoR), defined as the time from the Day 28 response (CR or PR) to the day of aGVHD recurrence/progression, new systemic therapy for aGVHD, or death from any cause, whichever occurs first. In addition, we will also consider variations on the DoR definition as detailed in section 3.3.2

• Treatments

  Therapies:

  Cell Therapy; Janus kinase (JAK) inhibitor

  Medications:

  Jakafi (Ruxolitinib); Placebo (); Remestemcel-L (); Ruxolitinib ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • Age 18 years or older at the time of enrollment.
  • Able to take oral medications.
  • Have Grade III-IV SR-aGVHD at the time of enrollment, defined as aGVHD resistant to high dose corticosteroids at a dose of ≥ 1 mg/kg/day methylprednisolone (or equivalent), given alone or in combination with GVHD prophylaxis agents such as CNI, mTOR inhibitor, or MMF.
  • Evident myeloid and platelet engraftment. Absolute neutrophil count (ANC) > 1000/mm3 and platelets ≥ 20,000/ mm3. Use of growth factor supplementation and transfusion support is allowed.
  • Minimum Karnofsky performance score of 30 at the time of study entry.
  • Patient (or legal representative where appropriate) must be capable of providing written informed consent/assent.
  • Female patients of childbearing potential must use a medically accepted method of contraception and must agree to continue use of this method for the entire duration of study participation. Acceptable methods of contraception include abstinence, barrier method with spermicide, intrauterine device, or steroid contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method.
  • Male patients with partners of childbearing potential must agree to use adequate contraception (barrier method with spermicide or abstinence) for the entire duration of study participation.
  • Willing and able to comply with study requirements, remain at the clinic, and return to the clinic for the follow-up evaluation, as specified in this protocol during the study period.

• Exclusion Criteria

  Key Exclusion Criteria:
  • Underwent second allogeneic hematopoietic cell transplantation within six months from the first transplant.
  • Received systemic treatment for aGVHD other than corticosteroids +/- agents used for aGVHD prophylaxis (e.g., CNIs, mTOR inhibitor, and/or MMF).
  • Respiratory disease requiring continuous positive pressure ventilation or intubation. Patients who need intermittent continuous positive airway pressure (e.g., during sleep) are eligible.
  • Any underlying or current medical or psychiatric condition that, in the opinion of the investigator, would interfere with the evaluation of the patient.
  • Post-transplant morphologic relapsed malignancy [defined as > 5% blasts on bone marrow examination and/or extramedullary relapse].
  • Donor leukocyte infusion (DLI) for treatment of malignant disease relapse. Patients who received DLI for indications other than relapse, including for treatment of minimal residual disease (MRD) and mixed chimerism, are eligible.
  • Prior treatment with any mesenchymal lineage cells, including remestemcel-L.
  • Active or inadequately treated latent infection with Mycobacterium tuberculosis (i.e., tuberculosis).
  • Female patients who are pregnant, lactating, or planning a pregnancy during the expected remestemcel-L treatment period.
  • Concurrently receiving an investigational agent, device or procedure. An investigational agent, device or procedure is defined as having no known FDA-approved indications. Any prior and/or current participation in a clinical trial of an investigational medicinal product (IMP) that is registered and being used off label requires review by the study's Protocol Officer, Protocol Chairs, and Sponsor prior to enrollment.
  • Known hypersensitivity to DMSO or to porcine or bovine proteins.
  • Requiring vasopressor support.
  • Uncontrolled infections. Infections are considered controlled if appropriate therapy has been instituted and, at the time of enrollment, no signs of progression are present. Persistent fever without other signs or symptoms will not be interpreted as progressing infection. Progression of infection is defined as: hemodynamic instability attributable to sepsis OR new symptoms attributable to infection OR worsening physical signs attributable to infection OR worsening radiographic findings attributable to infection. Patients with radiographic findings attributable to infection within 4 weeks prior to enrollment must have a repeat radiographic exam within one week of enrollment that documents stable or improved findings.
  • Estimated creatinine clearance less than 15 mL/min or those requiring hemodialysis.
  • Clinically significant liver disorders or bilirubin greater than 3 mg/dl not attributable to aGVHD or Gilbert's.
  • Moderate to severe cGVHD that require systemic treatment. Chronic GVHD that is not requiring systemic therapy is allowed.

If you are interested in learning more about clinical trials, our clinical trial navigators can discuss your options and recommend opportunities that may be suitable for you. Call 813-745-6100 or 1-800-679-0775 (toll-free) or submit a clinical trials inquiry form.