Sirolimus, Mycophenolate Mofetil and Bortezomib as Graft-Versus-Host Disease (GVHD) Prophylaxis After Reduced Intensity Conditioning (RIC) Hematopoietic Stem Cell Transplantation

Dana-Farber Cancer Institute

Status and phase: Terminated; Phase 2

Conditions: Graft-vs-Host Disease

Treatments: Drug: Sirolimus; Drug: Mycophenolate mofetil; Drug: Bortezomib

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00548717

DFCI 07-197

Details and patient eligibility

About

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.

Full 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.

Enrollment: 15 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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15 participants in 2 patient groups

Siro/MMF

Experimental group

Description:

Sirolimus and Mycophenolate Mofetil as GVHD Prophylaxis Sirolimus (Rapamycin); Mycophenolate Mofetil (MMF)

Treatment:

Drug: Mycophenolate mofetil

Drug: Sirolimus

Siro/MMF/Bort

Experimental group

Description:

Sirolimus, Mycophenolate Mofetil, and Bortezomib as GVHD Prophylaxis Sirolimus (Rapamycin); Mycophenolate Mofetil (MMF) Bortezomib (Velcade) \*added with study reopening in 2012

Treatment:

Drug: Bortezomib

Drug: Mycophenolate mofetil

Drug: Sirolimus