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

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ClinicalTrials.gov Identifier: NCT02728700
Recruitment Status : Recruiting
First Posted : April 5, 2016
Last Update Posted : April 5, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Stanford University

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.

Condition or disease Intervention/treatment Phase
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 Procedure: Allogeneic Hematopoietic Stem Cell Transplantation Other: Laboratory Biomarker Analysis Drug: Mycophenolate Mofetil Drug: Sirolimus Phase 1 Phase 2

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  (Clinical Trial)
Estimated Enrollment : 9 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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 Start Date : February 2016
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : August 2018


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.
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




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.



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Ages Eligible for Study:   3 Years to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02728700


Locations
United States, California
Stanford University, School of Medicine Recruiting
Palo Alto, California, United States, 94304
Contact: Gopin Saini    650-725-9032    gopin.saini@stanford.edu   
Principal Investigator: Rajni Agarwal-Hashmi         
Sponsors and Collaborators
Stanford University
National Cancer Institute (NCI)
Investigators
Principal Investigator: Rajni Agarwal-Hashmi Stanford Cancer Institute

Responsible Party: Stanford University
ClinicalTrials.gov Identifier: NCT02728700     History of Changes
Other Study ID Numbers: PEDSBMT295
NCI-2016-00387 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
34973 ( Other Identifier: Stanford IRB )
First Posted: April 5, 2016    Key Record Dates
Last Update Posted: April 5, 2018
Last Verified: April 2018

Additional relevant MeSH terms:
Lymphoma
Syndrome
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Lymphoma, Non-Hodgkin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Hodgkin Disease
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Primary Myelofibrosis
Leukemia, Myeloid, Chronic-Phase
Blast Crisis
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Myeloproliferative Disorders
Cell Transformation, Neoplastic
Carcinogenesis
Neoplastic Processes