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

NCT02728700 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: IRB-34973NCI-2016-00387PEDSBMT295
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to 60 days post-transplant

• 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.

  Up to 100 days post-transplant

Secondary Outcomes (5)

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

  Up to 100 days

• Incidence of venous-occlusive disease (VOD) using Modified Seattle Criteria

  Up to 100 days

• Severity of mucositis determined by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03

  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

  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

  Baseline to up to 100 days

Study Arms (1)

Treatment (sirolimus, HSCT, MMF)

EXPERIMENTAL

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; Other: Laboratory Biomarker Analysis; Drug: Mycophenolate Mofetil; Drug: Sirolimus

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo HSCT

Also known as: allogeneic stem cell transplantation, HSC, HSCT

Treatment (sirolimus, HSCT, MMF)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (sirolimus, HSCT, MMF)

Mycophenolate Mofetil DRUG

Given IV

Also known as: Cellcept, MMF

Treatment (sirolimus, HSCT, MMF)

Sirolimus DRUG

Given PO

Also known as: AY 22989, RAPA, Rapamune, RAPAMYCIN, SILA 9268A, WY-090217

Treatment (sirolimus, HSCT, MMF)

Eligibility Criteria

• Age: 3 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University, School of Medicine

Palo Alto, California, 94304, United States

Location

MeSH Terms

Conditions

Hodgkin Disease; Anemia, Refractory, with Excess of Blasts; Blast Crisis; Leukemia, Myeloid, Chronic-Phase; Primary Myelofibrosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Mycophenolic Acid; Sirolimus

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Anemia, Refractory; Anemia; Hematologic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases; Leukemia, Myeloid; Leukemia; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Macrolides; Lactones

Study Officials

• Rajni Agarwal-Hashmi

  Stanford Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2016
• First Posted: April 5, 2016
• Study Start: February 1, 2016
• Primary Completion: April 1, 2017
• Study Completion: July 1, 2018
• Last Updated: September 12, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)