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

NCT ID: NCT01220297

Last Updated: 2017-06-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-08-31
• Study Completion Date: 2011-08-31

Brief Summary

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)

Detailed 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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Carmustine Etoposide Cyclophosphamide

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

Group Type: EXPERIMENTAL

Sirolimus

Intervention Type: DRUG

Immunosuppressant administered orally to:

• Adults (age 14 and older), beginning on Day -3 with 12 mg loading dose, followed by 4 mg/day.
• Children < 13 years or weighing 40 kg, beginning on Day -3 with 3 mg/m² loading dose, followed by 1 mg/ m², rounded to the nearest full milligram.

Daily dosage may be adjusted to maintain a target serum trough level of 3 to 12 ng/ml. Sirolimus dose tapering will begin at Day 100 in the absence of GvHD, with the goal of discontinuation by 6 months.

Mycophenolate mofetil (MMF)

Intervention Type: DRUG

Immunosuppressant given intravenously (IV) at 15 mg/kg 3 times daily, starting on Day 0 ≥ 2 hr after the completion of the HSCT infusion. Dose of MMF will be based on actual body weight, but limited to 15 kg above ideal body weight. MMF dose tapering will begin at Day 100 in the absence of GvHD, with the goal of discontinuation by 6 months.

Carmustine

Intervention Type: DRUG

For Carmustine + Etoposide + Cyclophosphamide cohort, chemotherapy administered IV on Day -6 at the lesser of 15 mg/kg or 550 mg/m².

Etoposide

Intervention Type: DRUG

For Carmustine + Etoposide + Cyclophosphamide cohort, chemotherapy administered IV on Day -4 at 60 mg/kg

Cyclophosphamide (Cyclo, CY)

Intervention Type: DRUG

Cyclophosphamide is a chemotherapy agent.

For FTBI + Cyclophosphamide cohort, administered IV on Day -3 and -2 at 60 mg/kg.

For Carmustine + Etoposide + Cyclophosphamide cohort, administered IV on Day -2 at 100 mg/kg

FTBI + Cyclophosphamide

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

Group Type: EXPERIMENTAL

Sirolimus

Intervention Type: DRUG

Immunosuppressant administered orally to:

• Adults (age 14 and older), beginning on Day -3 with 12 mg loading dose, followed by 4 mg/day.
• Children < 13 years or weighing 40 kg, beginning on Day -3 with 3 mg/m² loading dose, followed by 1 mg/ m², rounded to the nearest full milligram.

Daily dosage may be adjusted to maintain a target serum trough level of 3 to 12 ng/ml. Sirolimus dose tapering will begin at Day 100 in the absence of GvHD, with the goal of discontinuation by 6 months.

Mycophenolate mofetil (MMF)

Intervention Type: DRUG

Immunosuppressant given intravenously (IV) at 15 mg/kg 3 times daily, starting on Day 0 ≥ 2 hr after the completion of the HSCT infusion. Dose of MMF will be based on actual body weight, but limited to 15 kg above ideal body weight. MMF dose tapering will begin at Day 100 in the absence of GvHD, with the goal of discontinuation by 6 months.

Cyclophosphamide (Cyclo, CY)

Intervention Type: DRUG

Cyclophosphamide is a chemotherapy agent.

For FTBI + Cyclophosphamide cohort, administered IV on Day -3 and -2 at 60 mg/kg.

For Carmustine + Etoposide + Cyclophosphamide cohort, administered IV on Day -2 at 100 mg/kg

FTBI

Intervention Type: DRUG

For FTBI + Cyclophosphamide cohort, administered as 1320 cGy delivered in 11 120 cGy fractions over 4 days starting on Day -7.

Interventions

Sirolimus

Immunosuppressant administered orally to:

• Adults (age 14 and older), beginning on Day -3 with 12 mg loading dose, followed by 4 mg/day.
• Children < 13 years or weighing 40 kg, beginning on Day -3 with 3 mg/m² loading dose, followed by 1 mg/ m², rounded to the nearest full milligram.

Daily dosage may be adjusted to maintain a target serum trough level of 3 to 12 ng/ml. Sirolimus dose tapering will begin at Day 100 in the absence of GvHD, with the goal of discontinuation by 6 months.

Intervention Type: DRUG

Mycophenolate mofetil (MMF)

Immunosuppressant given intravenously (IV) at 15 mg/kg 3 times daily, starting on Day 0 ≥ 2 hr after the completion of the HSCT infusion. Dose of MMF will be based on actual body weight, but limited to 15 kg above ideal body weight. MMF dose tapering will begin at Day 100 in the absence of GvHD, with the goal of discontinuation by 6 months.

Intervention Type: DRUG

Carmustine

For Carmustine + Etoposide + Cyclophosphamide cohort, chemotherapy administered IV on Day -6 at the lesser of 15 mg/kg or 550 mg/m².

Intervention Type: DRUG

Etoposide

For Carmustine + Etoposide + Cyclophosphamide cohort, chemotherapy administered IV on Day -4 at 60 mg/kg

Intervention Type: DRUG

Cyclophosphamide (Cyclo, CY)

Cyclophosphamide is a chemotherapy agent.

For FTBI + Cyclophosphamide cohort, administered IV on Day -3 and -2 at 60 mg/kg.

For Carmustine + Etoposide + Cyclophosphamide cohort, administered IV on Day -2 at 100 mg/kg

Intervention Type: DRUG

FTBI

For FTBI + Cyclophosphamide cohort, administered as 1320 cGy delivered in 11 120 cGy fractions over 4 days starting on Day -7.

Intervention Type: DRUG

Other Intervention Names

Rapamycin; Rapamune; Cellcept; Bis-chloroethylnitrosourea (BCNU, BiCNU); VP-16; VP16; Cytophosphane; Endoxan; total body irradiation

Eligibility 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).

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Laura Johnston

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Laura Johnston

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University School of Medicine

Stanford, California, United States

Countries

United States

Other Identifiers

SU-09092009-3841

Identifier Type: OTHER

Identifier Source: secondary_id

BMT209

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-14913

Identifier Type: -

Identifier Source: org_study_id