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

September 10, 2018 updated by: Stanford University

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

1

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94304
        • Stanford University, School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 30 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Mycophenolate Mofetil
Given IV
Other Names:
  • Cellcept
  • MMF
Drug: Sirolimus
Given PO
Other Names:
  • Rapamune
  • AY 22989
  • RAPA
  • RAPAMYCIN
  • SILA 9268A
  • WY-090217
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo HSCT
Other Names:
  • HSC
  • HSCT
  • allogeneic stem cell transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 60 days post-transplant
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.
Up to 100 days post-transplant

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 100 days
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.
Up to 100 days
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.
Up to 100 days
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.
Baseline to up to 100 days
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.
Baseline to up to 100 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stanford University

Investigators

  • Principal Investigator: Rajni Agarwal-Hashmi, Stanford Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2016

Primary Completion (Actual)

April 1, 2017

Study Completion (Actual)

July 1, 2018

Study Registration Dates

First Submitted

March 30, 2016

First Submitted That Met QC Criteria

March 30, 2016

First Posted (Estimate)

April 5, 2016

Study Record Updates

Last Update Posted (Actual)

September 12, 2018

Last Update Submitted That Met QC Criteria

September 10, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB-34973
  • NCI-2016-00387 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • PEDSBMT295 (Other Identifier: OnCore)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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