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
18 Years
55 Years
Both
Graft Versus Host Disease, Leukemia, Myelodysplastic Syndromes
Trial Information
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
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.
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)
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Supportive Care
Principal Investigator
Mary C. Territo, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Jonsson Comprehensive Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000358809
NCT ID:
NCT00081055
Start Date:
December 2003
Completion Date:
Related Keywords:
- Graft Versus Host Disease
- Leukemia
- Myelodysplastic Syndromes
- 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)
- Graft vs Host Disease
- Leukemia
- Myelodysplastic Syndromes
- Preleukemia
- Hematologic Neoplasms
Name | Location |
|---|---|
| Jonsson Comprehensive Cancer Center, UCLA | Los Angeles, California 90095-1781 |
