Clinical trial NCT00081055: OTI-010 for Graft-Versus-Host Disease Prophylaxis in Treating Patients Who Are Undergoing Donor Peripheral Stem Cell Transplantation for Hematologic Malignancies
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Graft Versus Host Disease
Leukemia
Myelodysplastic Syndromes
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)
Lead sponsor: Mesoblast, Ltd.
Sponsor class: INDUSTRY
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-04-08
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility 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)

Primary outcomes:
measure: Incidence of acute GVHD grade II-IV of skin, liver and gut (stomach to rectum) through Day 84 post-PBSC transplantation
timeFrame: Day 84
Secondary outcomes:
measure: Safety as measured by infusional toxicity, relapse nd survival, formation of potential ectopic tissue foci
timeFrame: 84 days
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
Study officials:
affiliation: Jonsson Comprehensive Cancer Center
name: Mary C. Territo, MD
role: PRINCIPAL_INVESTIGATOR
References: