Clinical trial NCT00350181: Sirolimus & Mycophenolate Mofetil as GVHD Prophylaxis in Myeloablative, Matched Related Donor HCT
Official title: Sirolimus and Mycophenolate Mofetil as GVHD Prophylaxis in Myeloablative, Matched Related Donor Hematopoietic Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Lymphoma, Non-Hodgkin
Hematologic Diseases
Acute GVHD
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2006-07-10
Enrollment: 11
Sex: ALL
Minimum age (years): 2
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: GVHD prophylaxis of sirolimus and mycophenolate mofetil for patients undergoing matched related allogeneic transplant for acute and chronic leukemia, MDS, high risk NHL and HL

Detailed description: To explore the novel combination of sirolimus and mycophenolate mofetil (MMF) as graft versus host disease (GVHD) prevention in HLA matched related donor blood or marrow transplantation (BMT). This study will report the toxicities associated with this drug combination and also explore possible correlations between specific blood cell types and antibody production during this therapy.

Eligibility criteria: Inclusion Criteria:

* Disease Categories: (one of the following)

  * AML, age 2 - 60 years beyond 2nd remission or relapsed/refractory disease
  * AML, age 51-60 years of age, in first or subsequent remission or relapsed/refractory disease
  * AML with multilineage dysplasia
  * ALL, age 2 - 60 years beyond 2nd remission or relapsed/refractory disease
  * ALL, age 51 - 60 years in first or subsequent remission or relapsed/refractory disease
  * CML Beyond 2nd chronic phase or in blast crisis
  * MDS; Includes World Health Organization classifications of refractory anemia with excess blasts-1 (RAEB-1), RAEB-2 and therapy-related MDS
  * Myeloproliferative disorders; MDS with poor long-term survival including myeloid metaplasia and myelofibrosis
  * High risk NHL in first remission
  * Relapsed or refractory NHL
  * HL beyond first remission
* Males and females of any ethnic background 2 - 60 years of age
* Karnofsky Performance Status ≥ 70% or Lansky performance status \> 70% for patients \< 16 years of age.
* Matched related donor identified: 6/6 HLA-A, B and DRB1
* Willingness to take oral medications during the transplantation period
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Prior myeloablative allogeneic or autologous HCT
* HIV infection
* Pregnant
* Lactating females
* Evidence of uncontrolled active infection
* Organ Dysfunction:
* Serum creatinine \> 1.5 mg/dL or 24 hour creatinine clearance \< 50 ml/min
* Direct bilirubin, ALT or AST \> 2 x ULN
* In adults DLCO \< 60% predicted and in children room air oxygen saturation \< 92%
* In adults, left ventricular ejection fraction \< 45% and in children, shortening fraction \< 26%
* Fasting Cholesterol \> 300 mg/dL or Triglycerides \> 300 mg/dL while on lipid-lowering agents.
* Patients receiving investigational drugs unless cleared by the PI.
* Patients with prior malignancies except basal cell carcinoma or treated carcinoma in-situ.
* Cancer treated with curative intent \> 5 years will be allowed.
* Cancer treated with curative intent ≤ 5 years will not be allowed with PI approval.

Primary outcomes:
measure: To evaluate the incidence of grade II-IV acute GVHD with sirolimus and mycophenolate mofetil GVHD prophylaxis.
timeFrame: D+100 post-transplant
Secondary outcomes:
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Laura Johnston
role: PRINCIPAL_INVESTIGATOR
References:
citation: Johnston L, Florek M, Armstrong R, McCune JS, Arai S, Brown J, Laport G, Lowsky R, Miklos D, Shizuru J, Sheehan K, Lavori P, Negrin R. Sirolimus and mycophenolate mofetil as GVHD prophylaxis in myeloablative, matched-related donor hematopoietic cell transplantation. Bone Marrow Transplant. 2012 Apr;47(4):581-8. doi: 10.1038/bmt.2011.104. Epub 2011 May 9.