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

Stanford University

Status and phase: Terminated; Phase 2

Conditions: Hodgkin Lymphoma; Non-Hodgkin Lymphoma (NHL); Acute-graft-versus-host Disease; Leukemia; Hematologic Diseases

Treatments: Drug: Cyclophosphamide (Cyclo, CY); Drug: Etoposide; Drug: Sirolimus; Drug: Carmustine; Drug: FTBI; Drug: Mycophenolate mofetil (MMF)

Study type: Interventional

Funder types: Other

Identifiers

NCT01220297

IRB-14913

BMT209 (Other Identifier)

SU-09092009-3841 (Other Identifier)

Details and patient eligibility

About

A continuation study of sirolimus and mycophenolate mofetil (MMF) for graft-vs-host disease (GvHD) prophylaxis for patients undergoing matched related allogeneic hematopoietic stem cell transplantation (HSCT) for acute and chronic leukemia, myelodysplastic syndrome (MDS), high risk non-Hodgkin lymphoma (NHL), or Hodgkin lymphoma (HL)

Full description

To explore the novel combination of sirolimus and mycophenolate mofetil (MMF) as graft-vs-host disease (GvHD) prevention in human leukocyte antigen (HLA)-matched related donor peripheral blood stem cell (PBSC) or marrow transplantation (BMT), collectively hematopoietic stem cell transplantation (HSCT). This study will report the toxicities associated with this drug combination.

For all treatments and procedures, Study Day is based on the day of HSCT as Day 0.

Enrollment: 3 patients

Sex: All

Ages: 2 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

INCLUSION CRITERIA

• Acute myelogenous leukemia (AML), beyond 2nd remission or relapsed/refractory disease, age 2 to 60 years
• AML, in first or subsequent remission or relapsed/refractory disease, age 51 to 60 years of age
• AML with multilineage dysplasia
• Acute lymphoblastic leukemia (ALL), beyond 2nd remission or relapsed/refractory disease, age 2 to 60 years
• ALL, age 51 - 60 years in first or subsequent remission or relapsed/refractory disease
• Chronic myeloid leukemia (CML), beyond 2nd chronic phase or in blast crisis
• Myelodysplastic syndrome (MDS), including World Health Organization (WHO)classifications of refractory anemia with excess blasts-1 (RAEB-1), RAEB-2 and therapy-related MDS
• MDS with poor long-term survival including myeloid metaplasia and myelofibrosis
• Myeloproliferative disorders
• High-risk non-Hodgkin lymphoma (NHL) in 1st emission
• Relapsed or refractory NHL
• Hodgkin lymphoma (HL) beyond first remission
• Males and females of any ethnic background, 2 to 60 years of age
• Karnofsky Performance Status (KPS) ≥ 70% or Lansky performance status > 70% for patients < 16 years of age.
• Related, matched-donor identified [6/6 human leukocyte antigen (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 hematopoietic stem cell transplant (HSCT)
• HIV infection
• Pregnant
• Lactating
• Evidence of uncontrolled active infection
• Serum creatinine > 1.5 mg/dL or 24-hour creatinine clearance < 50 mL/min
• Direct bilirubin, Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 x upper limit of normal (ULN)
• Carbon monoxide diffusing capacity (DlCO) < 60% predicted (adults) OR and in-room air oxygen saturation < 92% (children)
• Left ventricular ejection fraction < 45% (adults) OR shortening fraction < 26%(children)
• Fasting cholesterol > 300 mg/dL or Triglycerides > 300 mg/dL while on lipid-lowering agents.
• Receiving investigational drugs unless cleared by the Principal Investigator (PI).
• Prior malignancies except basal cell carcinoma or treated carcinoma in-situ.
• Cancer treated with curative intent ≤ 5 years (EXCEPTION BY PI DISCRETION) (Cancer treated with curative intent > 5 years will be allowed).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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3 participants in 2 patient groups

Carmustine Etoposide Cyclophosphamide

Experimental group

Description:

Carmustine + Etoposide + Cyclophosphamide followed by Sirolimus and Mycophenolate mofetil (MMF) as prophylaxis.

Treatment:

Drug: Mycophenolate mofetil (MMF)

Drug: Carmustine

Drug: Etoposide

Drug: Sirolimus

Drug: Cyclophosphamide (Cyclo, CY)

FTBI + Cyclophosphamide

Experimental group

Description:

FTBI + Cyclophosphamide followed by Sirolimus and Mycophenolate mofetil (MMF) as prophylaxis.

Treatment:

Drug: Mycophenolate mofetil (MMF)

Drug: FTBI

Drug: Sirolimus

Drug: Cyclophosphamide (Cyclo, CY)