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

Sponsor

Mesoblast International Sàrl (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT00081055

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Graft Versus Host Disease Leukemia Myelodysplastic Syndromes	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	Phase 2

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

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Masking:

Double

Primary Purpose:

Supportive Care

Official Title:

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Safety as measured by infusional toxicity, relapse nd survival, formation of potential ectopic tissue foci [84 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)