Clinical trial NCT02728700: 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
Overall status: TERMINATED
Phase: PHASE1
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
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2016-04-05
Enrollment: 1
Sex: ALL
Minimum age (years): 3
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Incidence of acute GvHD grade 3 & 4, according to the Glucksberg staging criteria
timeFrame: Up to 60 days post-transplant
measure: Incidence of acute GvHD grade 3 & 4, according to the Glucksberg staging criteria
timeFrame: Up to 100 days post-transplant
Secondary outcomes:
measure: Incidence of thrombotic microangiopathy defined according to the bone marrow transplant clinical trials network toxicity committee
timeFrame: Up to 100 days
measure: Incidence of venous-occlusive disease (VOD) using Modified Seattle Criteria
timeFrame: Up to 100 days
measure: Severity of mucositis determined by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03
timeFrame: Up to 100 days
measure: Time to neutrophil engraftment defined as first of 3 consecutive days with the absolute neutrophil count is > 500/ul in the peripheral blood
timeFrame: Baseline to up to 100 days
measure: 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
timeFrame: Baseline to up to 100 days
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University, School of Medicine
state: California
Study officials:
affiliation: Stanford Cancer Institute
name: Rajni Agarwal-Hashmi
role: PRINCIPAL_INVESTIGATOR
References: