OTI-010 for Graft-Versus-Host Disease Prophylaxis in Treating Patients Who Are Undergoing Donor Peripheral Stem Cell Transplantation for Hematologic Malignancies

Overview

RATIONALE: OTI-010 may be effective for graft-versus-host disease prophylaxis (prevention) in patients who are undergoing donor peripheral stem cell transplantation for hematologic malignancies (cancer of the blood or bone marrow). PURPOSE: This randomized phase II trial is studying how well OTI-010 works in preventing graft-versus-host disease in patients who are undergoing donor peripheral stem cell transplantation for hematologic cancer.

Full Title of Study: “A Phase II, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety and Efficacy of OTI-010 in Subjects Who Receive HLA-Identical Sibling Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Primary Purpose: Supportive Care
    • Masking: Double

Detailed Description

OBJECTIVES: – Compare the safety and efficacy of OTI-010 vs placebo as graft-versus-host disease prophylaxis in patients with hematologic malignancies undergoing HLA-identical sibling matched peripheral blood stem cell transplantation. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to age (18 to 34 vs 35 to 55) and donor/recipient gender (female donor/male recipient vs female donor/female recipient vs male donor/female recipient vs male donor/male recipient). – Conditioning regimen: Patients receive cyclophosphamide IV once daily on days -5 and -4 and undergo total body irradiation twice daily on days -3 to -1 OR busulfan IV over 2 hours every 6 hours on days -7 to -4 and cyclophosphamide IV once daily on days -3 and -2. – Graft-versus-host disease prophylaxis: Patients receive methotrexate IV on days 1, 3, 6, and 11. Patients also receive cyclosporine orally or IV (over 1-4 hours) twice daily beginning on day -1 and continuing for at least 6 months followed by a taper until 1 year after transplantation. – OTI-010 therapy: Patients are randomized to 1 of 3 treatment arms. – Arm I: Patients receive placebo IV 4 hours before peripheral blood stem cell transplantation (PBSCT) on day 0. – Arm II: Patients receive OTI-010 IV 4 hours before PBSCT on day 0. – Arm III: Patients receive a higher dose of OTI-010 IV 4 hours before PBSCT on day 0. – Allogeneic stem cell transplantation: Patients undergo allogeneic PBSCT on day 0. Patients are followed at 18 weeks, at 6, 9, and 12 months, every 6 months for 1 year, and then annually for 3 years. PROJECTED ACCRUAL: A total of 99 patients (33 per treatment arm) will be accrued for this study within 5 months.

Interventions

  • Biological: autologous expanded mesenchymal stem cells OTI-010
  • Drug: busulfan
  • Drug: cyclophosphamide
  • Drug: cyclosporine
  • Drug: methotrexate
  • Procedure: peripheral blood stem cell transplantation
  • Radiation: radiation therapy

Clinical Trial Outcome Measures

Primary Measures

  • Incidence of acute GVHD grade II-IV of skin, liver and gut (stomach to rectum) through Day 84 post-PBSC transplantation
    • Time Frame: Day 84

Secondary Measures

  • Safety as measured by infusional toxicity, relapse nd survival, formation of potential ectopic tissue foci
    • Time Frame: 84 days

Participating in This Clinical Trial

DISEASE CHARACTERISTICS:

  • Histologically confirmed diagnosis of 1 of the following hematologic malignancies: – Acute lymphoblastic leukemia, meeting 1 of the following criteria: – In first or second remission – In early first or second relapse* – Acute myeloid leukemia, meeting 1 of the following criteria: – In first or second remission – In early first or second relapse* – Chronic myelogenous leukemia – Chronic or accelerated phase – Any of the following myelodysplastic syndromes: – Refractory anemia (RA) – RA with ringed sideroblasts – RA with excess blasts NOTE: *< 24% marrow blasts and < 5% peripheral blood blasts (within 10 days of beginning conditioning regimen) – No secondary acute leukemia – Prior CNS tumor involvement allowed provided patient is asymptomatic and there is no evidence of CNS disease on lumbar puncture and CT scan of the brain – Must have a 6/6 HLA-identical sibling donor available PATIENT CHARACTERISTICS: Age – 18 to 55 Performance status – Karnofsky 70-100% Life expectancy – Not specified Hematopoietic – Not specified Hepatic – Bilirubin < 2 times upper limit of normal (ULN) – SGOT < 10 times ULN – Hepatitis B core antigen, surface antigen, and e-antigen negative – Hepatitis B DNA negative – Hepatitis C RNA negative Renal – Creatinine clearance ≥ 60 mL/min Cardiovascular – LVEF ≥ 50% by MUGA or echocardiogram – No right sided heart failure Pulmonary – FEV_1 > 50% of predicted – DLCO ≥ 50% of predicted (corrected for anemia) – Oxygen saturation ≥ 97% on room air – No pulmonary hypertension Immunologic – HIV-1 and 2 antibody negative – HIV-1 antigen negative – HTLV-I and II antibody negative – No active infection Other – CNS function normal – No uncontrolled alcohol or substance abuse within the past 6 months – No other concurrent underlying medical condition that would preclude study participation – Not pregnant – Negative pregnancy test – Fertile patients must use 2 effective methods of contraception PRIOR CONCURRENT THERAPY: Biologic therapy – No prior allogeneic or autologous hematopoietic stem cell transplantation – No concurrent medication to accelerate neutrophil or platelet engraftment except filgrastim (G-CSF) Chemotherapy – Not specified Endocrine therapy – Not specified Radiotherapy – Not specified Surgery – No prior solid organ transplantation Other – More than 30 days since prior investigational agents or devices – No other concurrent investigational agents or devices – No concurrent anti-infective therapy except prophylactic therapy – No other concurrent conditioning regimen agents – No concurrent herbal remedies except multivitamins – No other concurrent graft-versus-host disease prophylaxis medications (e.g., ursodeoxycholic acid)

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 55 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Mesoblast International Sàrl
  • Collaborator
    • National Cancer Institute (NCI)
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Mary C. Territo, MD, Principal Investigator, Jonsson Comprehensive Cancer Center

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