Clinical trial NCT00548717: Sirolimus, Mycophenolate Mofetil and Bortezomib as Graft-Versus-Host Disease (GVHD) Prophylaxis After Reduced Intensity Conditioning (RIC) Hematopoietic Stem Cell Transplantation
Official title: Sirolimus, Mycophenolate Mofetil and Bortezomib as Graft-Versus-Host Disease Prophylaxis After Non-Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Graft-vs-Host Disease
Keywords: GVHD
Stem cell transplantation
Sirolimus
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Wyeth is now a wholly owned subsidiary of Pfizer
name: PDL BioPharma, Inc.
First posted: 2007-10-24
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: This trial will test the hypothesis that the combination of sirolimus, mycophenolate mofetil, and bortezomib will be effective in preventing both acute and chronic GVHD after reduced intensity allogeneic stem cell transplantation.

Detailed description: The combination of tacrolimus and methotrexate is standard therapy for prevention of GVHD, however, our recent experience has demonstrated that the substitution of sirolimus for methotrexate provides superior GVHD control with reduced transplant-related toxicity. One limitation to the use of calcineurin inhibitors in GVHD prevention is the disruption in Treg function and proliferation. Based on our evolving understanding of the role of Treg in the development of chronic GVHD, we propose a GVHD prophylactic regimen that is effective in prevention of acute GVHD, but by virtue of the maintenance of Treg activity may be able to prevent chronic GVHD. We hypothesize that the substitution of mycophenolate mofetil for tacrolimus as well as the addition of bortezomib may provide similar protection against acute GVHD and prevent chronic GVHD while minimizing renal toxicity after transplantation.

Eligibility criteria: Inclusion Criteria:

1. Patients with hematologic malignancies, who are at high risk of complications after conventional myeloablative transplantation
2. Patients must have a 6/6 matched, related donor. Matching at HLA Class II will be based on PCR of sequence specific primers (SSP). Among family member transplants, serologic matching at Class I is sufficient
3. Patient age greater than 18
4. Performance status 0-2
5. Life expectancy of \> 100 days without transplantation
6. Written informed consent must be obtained in all cases from the patient

Exclusion Criteria:

1. Pregnancy
2. Prior Allogeneic Stem Cell Transplantation from any donor
3. Evidence of HIV infection or active Hepatitis B or C infection
4. Heart failure uncontrolled by medications
5. Total bilirubin \> 2.0 mg/dl that is due to hepatocellular dysfunction
6. AST \> 90
7. Cholesterol \> 300 mg/dl or Triglycerides \> 400 mg/dl while adequately treated
8. Uncontrolled bacterial, viral or fungal infection
9. Requirement for voriconazole at the time of hospital admission

Primary outcomes:
measure: To Determine the Rate of Grade II-IV Acute GVHD When Sirolimus and Mycophenolate Mofetil or Sirolimus, Mycophenolate Mofetil and Bortezomib is Used for GVHD Prophylaxis After Allogeneic Stem Cell Transplantation in Patients With Hematologic Malignancies
timeFrame: 150 days
Secondary outcomes:
measure: Donor Stem Cell Engraftment, Including Donor-host Hematopoietic Chimerism Studies Post Transplant
timeFrame: 30 days
measure: The Rate of Renal Insufficiency
timeFrame: 1 year
measure: To Correlate the Serum Concentrations of Mycophenolate Mofetil and Its Metabolites With Acute GVHD Incidence
timeFrame: 1 year
measure: Incidence of 100 Day Mortality
timeFrame: 100 days
measure: Incidence of Chronic GVHD
timeFrame: 1 year
measure: Overall Survival
timeFrame: 1 year
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Corey Cutler, MD
role: PRINCIPAL_INVESTIGATOR
References: