Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Sirolimus and Mycophenolate Mofetil in Preventing GVHD in Patients With Hematologic Malignancies Undergoing HSCT

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02728700
Recruitment Status : Terminated (Accrual factor)
First Posted : April 5, 2016
Last Update Posted : September 12, 2018
Sponsor:
Information provided by (Responsible Party):
Stanford University

Tracking Information
First Submitted Date  ICMJE March 30, 2016
First Posted Date  ICMJE April 5, 2016
Last Update Posted Date September 12, 2018
Study Start Date  ICMJE February 2016
Actual Primary Completion Date April 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 30, 2016)
  • Incidence of acute GvHD grade 3 & 4, according to the Glucksberg staging criteria [ Time Frame: Up to 60 days post-transplant ]
    Statistical analysis results will be reported using summary tables, figures, and data listings. Continuous variables will be summarized using the mean, standard deviation, median, minimum, and maximum.
  • Incidence of acute GvHD grade 3 & 4, according to the Glucksberg staging criteria [ Time Frame: Up to 100 days post-transplant ]
    Statistical analysis results will be reported using summary tables, figures, and data listings. Continuous variables will be summarized using the mean, standard deviation, median, minimum, and maximum.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 30, 2016)
  • Incidence of thrombotic microangiopathy defined according to the bone marrow transplant clinical trials network toxicity committee [ Time Frame: Up to 100 days ]
    Defined as: red blood cell fragmentation and at least two schistocytes per high-power field on peripheral smear; concurrent increased serum lactate dehydrogenase measurement above institutional baseline; concurrent doubling of serum creatinine or 50% increase in creatinine clearance from baseline and/or neurological dysfunction without other explanations; and negative direct and indirect Coombs. Statistical analysis results will be reported using summary tables, figures, and data listings. Continuous variables will be summarized using the mean, standard deviation, median, minimum, and maximum.
  • Incidence of venous-occlusive disease (VOD) using Modified Seattle Criteria [ Time Frame: Up to 100 days ]
    Severe VOD will be considered a dose limiting toxicity. Statistical analysis results will be reported using summary tables, figures, and data listings. Continuous variables will be summarized using the mean, standard deviation, median, minimum, and maximum.
  • Severity of mucositis determined by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 [ Time Frame: Up to 100 days ]
    Grade III and IV will be considered dose limiting toxicities. Statistical analysis results will be reported using summary tables, figures, and data listings. Categorical variables will be summarized by numbers and percentages of subjects in corresponding categories.
  • Time to neutrophil engraftment defined as first of 3 consecutive days with the absolute neutrophil count is > 500/ul in the peripheral blood [ Time Frame: Baseline to up to 100 days ]
    Statistical analysis results will be reported using summary tables, figures, and data listings. Continuous variables will be summarized using the mean, standard deviation, median, minimum, and maximum.
  • Time to platelet engraftment defined as the first day of a minimum of three consecutive measurements on different days when platelet count > 50,000/mm^3 and patient is transfusion-independent for a minimum of 7 days [ Time Frame: Baseline to up to 100 days ]
    Statistical analysis results will be reported using summary tables, figures, and data listings. Continuous variables will be summarized using the mean, standard deviation, median, minimum, and maximum.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sirolimus and Mycophenolate Mofetil in Preventing GVHD in Patients With Hematologic Malignancies Undergoing HSCT
Official Title  ICMJE Pilot Safety and Feasibility Trial of Mycophenolate and Sirolimus for Prevention of GVHD in Mismatched Unrelated and Related Donor Hematopoietic Stem Cell Transplantation for Hematologic Malignancies
Brief Summary This pilot phase I/II trial studies the side effects and how well sirolimus and mycophenolate mofetil work in preventing graft versus host disease (GvHD) in patients with hematologic malignancies undergoing hematopoietic stem cell transplant (HSCT). Biological therapies, such as sirolimus and mycophenolate mofetil, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop tumor cells from growing. Giving sirolimus and mycophenolate mofetil after hematopoietic stem cell transplant may be better in preventing graft-versus-host disease.
Detailed Description

PRIMARY OBJECTIVES:

I. Evaluate the safety and feasibility of administering sirolimus and mycophenolate mofetil (MMF) as prophylaxis of grade III-IV acute graft versus host disease (aGvHD) in patients undergoing mismatched unrelated and related donor hematopoietic stem cell transplant (HSCT).

OUTLINE:

Patients receive sirolimus orally (PO) starting on day -3, 3 times a week during hospitalization and then once a week for up to 6 months. Patients undergo HSCT on day 0. Patients also receive mycophenolate mofetil intravenously (IV) or PO three times a day (TID) on days 1-180. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at days 30, 60, 100, 180, 270, and 365, and then yearly thereafter.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Adult Hodgkin Lymphoma
  • Adult Myelodysplastic Syndrome
  • Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Childhood Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Childhood Hodgkin Lymphoma
  • Childhood Myelodysplastic Syndrome
  • Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Myelofibrosis
  • Primary Myelofibrosis
  • Recurrent Adult Acute Lymphoblastic Leukemia
  • Recurrent Adult Acute Myeloid Leukemia
  • Recurrent Adult Non-Hodgkin Lymphoma
  • Recurrent Childhood Acute Lymphoblastic Leukemia
  • Recurrent Childhood Acute Myeloid Leukemia
  • Recurrent Childhood Non-Hodgkin Lymphoma
  • Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Refractory Non-Hodgkin Lymphoma
Intervention  ICMJE
  • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
    Undergo HSCT
    Other Names:
    • allogeneic stem cell transplantation
    • HSC
    • HSCT
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Mycophenolate Mofetil
    Given IV
    Other Names:
    • Cellcept
    • MMF
  • Drug: Sirolimus
    Given PO
    Other Names:
    • AY 22989
    • RAPA
    • Rapamune
    • RAPAMYCIN
    • SILA 9268A
    • WY-090217
Study Arms  ICMJE Experimental: Treatment (sirolimus, HSCT, MMF)
Patients receive sirolimus PO starting on day -3, 3 times a week during hospitalization and then once a week for up to 6 months. Patients undergo HSCT on day 0. Patients also receive mycophenolate mofetil IV or PO TID on days 1-180. Treatment continues in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
  • Other: Laboratory Biomarker Analysis
  • Drug: Mycophenolate Mofetil
  • Drug: Sirolimus
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: August 21, 2018)
1
Original Estimated Enrollment  ICMJE
 (submitted: March 30, 2016)
9
Actual Study Completion Date  ICMJE July 2018
Actual Primary Completion Date April 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subjects must have one of the following disease categories:

    • Acute myeloid leukemia (AML) beyond 2nd remission or relapsed/refractory disease
    • Acute lymphoblastic leukemia (ALL) beyond 2nd remission or relapsed/refractory disease
    • Chronic myeloid leukemia (CML) beyond 2nd chronic phase or in blast crises
    • Myelodysplastic syndrome (MDS)
    • Myeloproliferative disorders including myeloid metaplasia and myelofibrosis
    • High risk non-Hodgkin's lymphoma (NHL) in first remission
    • Relapsed or refractory NHL
    • Hodgkin's lymphoma (HL) beyond first remission
  • Performance status by Karnofsky of >= 70% or Lansky > 70% for patients < 16 years of age
  • Human leukocyte antigen (HLA) mismatched related or unrelated donor identified 8/10 or 9/10
  • Willingness to take oral medications during the transplantation period
  • Willingness and ability to sign a written informed consent (assent if applicable)

Exclusion Criteria:

  • Prior myeloablative allogeneic or autologous HSCT
  • Human immunodeficiency virus (HIV) infection
  • Pregnant or lactating females
  • Evidence of uncontrolled active infection
  • Down syndrome
  • Serum creatinine (CR) < 1.5mg/dl or 24 hour CR clearance < 50 ml/min
  • Direct bilirubin > 2 x upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 x ULN
  • Carbon monoxide diffusing capability test (DLCO) > 60% predicted and in children- room air oxygen saturation > 92%
  • Left ventricular ejection fraction < 45% and in children-shortening fraction < 26%
  • Fasting cholesterol > 300 mg/dl or triglycerides > 300 while on lipid lowering agents
  • Patients who have received an investigational drug within 30 days of enrollment in study
  • Patients with prior malignancies except basal cell carcinoma or treated carcinoma in-situ; cancer treated with curative intent > 5 years will be allowed; cancer treatment with curative intent =< 5 years will not be allowed
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Years to 30 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02728700
Other Study ID Numbers  ICMJE IRB-34973
NCI-2016-00387 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
PEDSBMT295 ( Other Identifier: OnCore )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Stanford University
Study Sponsor  ICMJE Stanford University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Rajni Agarwal-Hashmi Stanford Cancer Institute
PRS Account Stanford University
Verification Date August 2018

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