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

NCT ID: NCT02728700

Last Updated: 2018-09-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2018-07-31

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Allogeneic Hematopoietic Stem Cell Transplantation

Intervention Type: PROCEDURE

Undergo HSCT

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Mycophenolate Mofetil

Intervention Type: DRUG

Given IV

Sirolimus

Intervention Type: DRUG

Given PO

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation

Undergo HSCT

Intervention Type: PROCEDURE

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Mycophenolate Mofetil

Given IV

Intervention Type: DRUG

Sirolimus

Given PO

Intervention Type: DRUG

Other Intervention Names

allogeneic stem cell transplantation; HSC; HSCT; Cellcept; MMF; AY 22989; RAPA; Rapamune; RAPAMYCIN; SILA 9268A; WY-090217

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

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rajni Agarwal-Hashmi

Role: PRINCIPAL_INVESTIGATOR

Stanford Cancer Institute

Locations

Stanford University, School of Medicine

Palo Alto, California, United States

Countries

United States

Other Identifiers

NCI-2016-00387

Identifier Type: REGISTRY

Identifier Source: secondary_id

PEDSBMT295

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-34973

Identifier Type: -

Identifier Source: org_study_id