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

December 3, 2014 updated by: Mesoblast International Sàrl

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

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095-1678
        • Jonsson Comprehensive Cancer Center, UCLA

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Day 84

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mesoblast International Sàrl

Collaborators

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

First Submitted

April 7, 2004

First Submitted That Met QC Criteria

April 7, 2004

First Posted (Estimate)

April 8, 2004

Study Record Updates

Last Update Posted (Estimate)

December 4, 2014

Last Update Submitted That Met QC Criteria

December 3, 2014

Last Verified

December 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Mesoblast
  • UCLA-0303036
  • CDR0000358809 (Registry Identifier: PDQ (Physician Data Query))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Myelodysplastic Syndromes

Clinical Trials on cyclophosphamide

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Moldova

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe