Graft Versus Host Disease, Leukemia, Myelodysplastic Syndromes
Conditions
Keywords
graft versus host disease, adult acute lymphoblastic leukemia in remission, recurrent adult acute lymphoblastic leukemia, adult acute myeloid leukemia in remission, recurrent adult acute myeloid leukemia, accelerated phase chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, refractory anemia, refractory anemia with excess blasts, refractory anemia with ringed sideroblasts, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with t(15;17)(q22;q12)
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.
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
BIOLOGICALautologous expanded mesenchymal stem cells OTI-010
DRUGbusulfan
DRUGcyclophosphamide
DRUGcyclosporine
DRUGmethotrexate
PROCEDUREperipheral blood stem cell transplantation
RADIATIONradiation therapy
Sponsors
National Cancer Institute (NCI)
Mesoblast International Sàrl
Study design
Allocation
RANDOMIZED
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of acute GVHD grade II-IV of skin, liver and gut (stomach to rectum) through Day 84 post-PBSC transplantation | Day 84 |
Secondary
| Measure | Time frame |
|---|---|
| Safety as measured by infusional toxicity, relapse nd survival, formation of potential ectopic tissue foci | 84 days |
Countries
United States
Outcome results
None listed