Sirolimus & Mycophenolate Mofetil as GVHD Prophylaxis in Myeloablative, Matched Related Donor HCT

Stanford University

Status and phase: Completed; Phase 2

Conditions: Acute GVHD; Leukemia; Lymphoma, Non-Hodgkin; Hematologic Diseases

Treatments: Drug: MMF; Drug: VP-16; Drug: BCNU; Drug: BU; Drug: FTBI; Drug: CY; Drug: Sirolimus

Study type: Interventional

Funder types: Other

Identifiers

NCT00350181

97168

BMT184

6112

IRB-06112

Details and patient eligibility

About

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

Full 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.

Enrollment: 11 patients

Sex: All

Ages: 2 to 60 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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11 participants in 3 patient groups

Regimen Treatment 1

Experimental group

Description:

For subjects 18-60 years old with lymphoma: (BCNU+ VP-16 +CY) BCNU 15 mg / kg (maximum dose 550 mg/m² actual body weight) on day -6. VP 60 mg / kg on day 4 and CY 100 mg / kg on day -2. Followed by Sirolimus and MMF as prophylaxis

Treatment:

Drug: Sirolimus

Drug: CY

Drug: BCNU

Drug: VP-16

Drug: MMF

Regimen Treatment 2

Experimental group

Description:

For subjects 18-50 years old with AML, ALL or CML: (VP-16 +CY+ FBI) Patients aged 18-50 years with AML, ALL or CML: FTBI 1320 cGy delivered in 11 120 cGy fractions over 4 days on days -8 through -5. VP 60 mg / kg on day -4 and CY 60 mg / kg on day -2. Followed by Sirolimus and MMF as prophylaxis

Treatment:

Drug: Sirolimus

Drug: FTBI

Drug: CY

Drug: VP-16

Drug: MMF

Regimen Treatment 3

Experimental group

Description:

For subjects 51-60 years with MDS, AML or ALL or 18-60 with MDS, secondary AML pr non-CML myeloproliferative disease: (BU+ VP-16 +CY) BU 1 mg/kg every 6 hours X 14 doses on days -9 through -6 with target concentration at steady state of X 800 ng / ml based on first dose pharmacokinetics. VP 60 mg / kg on day -5 and CY 45 mg / kg per day -2 days on day -3 and day -2. Followed by Sirolimus and MMF as prophylaxis

Treatment:

Drug: Sirolimus

Drug: CY

Drug: BU

Drug: VP-16

Drug: MMF