search
Back to results

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

Primary Purpose

Adult Hodgkin Lymphoma, Adult Myelodysplastic Syndrome, Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Allogeneic Hematopoietic Stem Cell Transplantation
Laboratory Biomarker Analysis
Mycophenolate Mofetil
Sirolimus
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Adult Hodgkin Lymphoma

Eligibility Criteria

3 Years - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Stanford University, School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (sirolimus, HSCT, MMF)

Arm Description

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.

Outcomes

Primary Outcome Measures

Incidence of acute GvHD grade 3 & 4, according to the Glucksberg staging criteria
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
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.

Secondary Outcome Measures

Incidence of thrombotic microangiopathy defined according to the bone marrow transplant clinical trials network toxicity committee
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
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
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
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
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.

Full Information

First Posted
March 30, 2016
Last Updated
September 10, 2018
Sponsor
Stanford University
search

1. Study Identification

Unique Protocol Identification Number
NCT02728700
Brief Title
Sirolimus and Mycophenolate Mofetil in Preventing GVHD in Patients With Hematologic Malignancies Undergoing HSCT
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Terminated
Why Stopped
Accrual factor
Study Start Date
February 2016 (undefined)
Primary Completion Date
April 2017 (Actual)
Study Completion Date
July 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Stanford University

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (sirolimus, HSCT, MMF)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Allogeneic Hematopoietic Stem Cell Transplantation
Other Intervention Name(s)
allogeneic stem cell transplantation, HSC, HSCT
Intervention Description
Undergo HSCT
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Mycophenolate Mofetil
Other Intervention Name(s)
Cellcept, MMF
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Sirolimus
Other Intervention Name(s)
AY 22989, RAPA, Rapamune, RAPAMYCIN, SILA 9268A, WY-090217
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Incidence of acute GvHD grade 3 & 4, according to the Glucksberg staging criteria
Description
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 Frame
Up to 60 days post-transplant
Title
Incidence of acute GvHD grade 3 & 4, according to the Glucksberg staging criteria
Description
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 Frame
Up to 100 days post-transplant
Secondary Outcome Measure Information:
Title
Incidence of thrombotic microangiopathy defined according to the bone marrow transplant clinical trials network toxicity committee
Description
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.
Time Frame
Up to 100 days
Title
Incidence of venous-occlusive disease (VOD) using Modified Seattle Criteria
Description
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.
Time Frame
Up to 100 days
Title
Severity of mucositis determined by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03
Description
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 Frame
Up to 100 days
Title
Time to neutrophil engraftment defined as first of 3 consecutive days with the absolute neutrophil count is > 500/ul in the peripheral blood
Description
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 Frame
Baseline to up to 100 days
Title
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
Description
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 Frame
Baseline to up to 100 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rajni Agarwal-Hashmi
Organizational Affiliation
Stanford Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University, School of Medicine
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs