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

This study has been terminated.
(Low accrual)
Sponsor:
Information provided by (Responsible Party):
Laura Johnston, Stanford University
ClinicalTrials.gov Identifier:
NCT01220297
First received: November 24, 2009
Last updated: May 31, 2017
Last verified: May 2017
November 24, 2009
May 31, 2017
August 2006
August 2010   (Final data collection date for primary outcome measure)
Acute Graft-vs-Host Disease (GvHD) (Grade 2 to 4) [ Time Frame: 100 days post-transplant ]

Assessed as the incidence of grade 2 to 4 acute graft-vs-host disease (GvHD) at Day 100 post-transplant.

Stage of Acute GvHD was assessed as follows.

  • Stage 1: Skin: rash < 25% of skin. Liver: bilirubin 2 to 3 mg/dL. Gut: diarrhea > 500 mL/day or persistent nausea with positive biopsy for GvHD
  • Stage 2: Skin: rash 25 to 50% of skin. Liver: bilirubin 3 to 6 mg/dL. Gut: diarrhea >1000 mL/day.
  • Stage 3: Skin: rash > 50% of skin. Liver: bilirubin 6 to 15 mg/dL. Gut: diarrhea > 1500 mL/day.
  • Stage 4: Skin: generalized erythroderma with bulla formation. Liver: bilirubin > 15 mg/dL. Gut: severe abdominal pain with or without ileus

Grade of Acute GvHD was determined as follows.

  • Grade 1: Stage 1-2 Skin + No Liver stage + No Gut stage
  • Grade 2: Stage 3 Skin OR Stage 1 Liver or Stage 1 Gut
  • Grade 3: No Skin stage + Stage 2 to 3 Liver Stage 2 to 4 Gut
  • Grade 4: Stage 4 Skin + or Stage 2 to 3 Liver + No Gut stage
Incidence of grade II-IV acute GVHD at D+100 post-transplant [ Time Frame: 100 days post-transplant ]
Complete list of historical versions of study NCT01220297 on ClinicalTrials.gov Archive Site
  • Acute GvHD (Grade 3 to 4) [ Time Frame: 100 days post-transplant ]

    Assessed as the incidence of grade 3 to 4 acute GvHD at Day 100 post-transplant.

    Stage of Acute GvHD was assessed as follows.

    • Stage 1: Skin: rash < 25% of skin. Liver: bilirubin 2 to 3 mg/dL. Gut: diarrhea > 500 mL/day or persistent nausea with positive biopsy for GvHD
    • Stage 2: Skin: rash 25 to 50% of skin. Liver: bilirubin 3 to 6 mg/dL. Gut: diarrhea >1000 mL/day.
    • Stage 3: Skin: rash > 50% of skin. Liver: bilirubin 6 to 15 mg/dL. Gut: diarrhea > 1500 mL/day.
    • Stage 4: Skin: generalized erythroderma with bulla formation. Liver: bilirubin > 15 mg/dL. Gut: severe abdominal pain with or without ileus

    Grade of Acute GvHD was determined as follows.

    • Grade 1: Stage 1-2 Skin + No Liver stage + No Gut stage
    • Grade 2: Stage 3 Skin OR Stage 1 Liver or Stage 1 Gut
    • Grade 3: No Skin stage + Stage 2 to 3 Liver Stage 2 to 4 Gut
    • Grade 4: Stage 4 Skin + or Stage 2 to 3 Liver + No Gut stage
  • Disease-free Survival (DFS) [ Time Frame: 2 years ]
    Assessed as survival without recurrence of disease
  • Overall Survival [ Time Frame: 2 years ]
    Overall survival is defined as time from enrollment to time of death or last follow-up, within 2 years.
  • Veno-occlusive Disease (VoD) [ Time Frame: 100 days post-transplant ]
    Assessed as the incidence of veno-occlusive disease (VoD) at 100 days post-transplant.
  • Grade III-IV acute GVHD [ Time Frame: D100 post-transplan ]
  • Pharmacokinetics of MMF [ Time Frame: completion of study- at 2-3 years after institution ]
  • Veno-occlusive Disease Incidence of Infection CMV reactivation [ Time Frame: VOD- ]
  • Chronic GVHD Disease-free and Overall Survival [ Time Frame: approximately 1-2 years after completion of the study ]
  • Time to neutrophil and platelet engraftment Thrombotic microangiopathy Severity of Mucositis [ Time Frame: Time to neutrophil and platelet engraftment: D100 post-transplant per patient Thrombotic microangiopathy- as it occurs and/or D100 post-transplant Mucositis- first 3 weeks post-transplant per patient; all patients - reviewed at completion of trial ]
Not Provided
Not Provided
 
Sirolimus & Mycophenolate Mofetil as GvHD Prophylaxis in Myeloablative, Matched Related Donor HCT
Sirolimus and Mycophenolate Mofetil as GvHD Prophylaxis in Myeloablative, Matched Related Donor Hematopoietic Cell Transplantation
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)

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.

Interventional
Phase 2
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
  • Hematologic Diseases
  • Acute-graft-versus-host Disease
  • Leukemia
  • Non-Hodgkin Lymphoma (NHL)
  • Hodgkin Lymphoma
  • Drug: 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.

    Other Names:
    • Rapamycin
    • Rapamune
  • 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.
    Other Name: Cellcept
  • Drug: Carmustine
    For Carmustine + Etoposide + Cyclophosphamide cohort, chemotherapy administered IV on Day -6 at the lesser of 15 mg/kg or 550 mg/m².
    Other Name: Bis-chloroethylnitrosourea (BCNU, BiCNU)
  • Drug: Etoposide
    For Carmustine + Etoposide + Cyclophosphamide cohort, chemotherapy administered IV on Day -4 at 60 mg/kg
    Other Names:
    • VP-16
    • VP16
  • 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

    Other Names:
    • Cytophosphane
    • Endoxan
  • Drug: FTBI
    For FTBI + Cyclophosphamide cohort, administered as 1320 cGy delivered in 11 120 cGy fractions over 4 days starting on Day -7.
    Other Name: total body irradiation
  • Experimental: Carmustine Etoposide Cyclophosphamide
    Carmustine + Etoposide + Cyclophosphamide followed by Sirolimus and Mycophenolate mofetil (MMF) as prophylaxis.
    Interventions:
    • Drug: Sirolimus
    • Drug: Mycophenolate mofetil (MMF)
    • Drug: Carmustine
    • Drug: Etoposide
    • Drug: Cyclophosphamide (Cyclo, CY)
  • Experimental: FTBI + Cyclophosphamide
    FTBI + Cyclophosphamide followed by Sirolimus and Mycophenolate mofetil (MMF) as prophylaxis.
    Interventions:
    • Drug: Sirolimus
    • Drug: Mycophenolate mofetil (MMF)
    • Drug: Cyclophosphamide (Cyclo, CY)
    • Drug: FTBI
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
3
August 2011
August 2010   (Final data collection date for primary outcome measure)

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).
Sexes Eligible for Study: All
2 Years to 60 Years   (Child, Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01220297
IRB-14913
SU-09092009-3841 ( Other Identifier: Stanford University )
BMT209 ( Other Identifier: OnCore )
No
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
No
Not Provided
Laura Johnston, Stanford University
Stanford University
Not Provided
Principal Investigator: Laura Johnston Stanford University
Stanford University
May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP