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

Stanford University

Status and phase: Terminated; Phase 1

Conditions: Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Myelofibrosis; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Adult Myelodysplastic Syndrome; Recurrent Childhood Acute Myeloid Leukemia; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Childhood Hodgkin Lymphoma; Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Childhood Myelodysplastic Syndrome; Childhood Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Adult Hodgkin Lymphoma; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Refractory Non-Hodgkin Lymphoma

Treatments: Drug: Mycophenolate Mofetil; Other: Laboratory Biomarker Analysis; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Sirolimus

Study type: Interventional

Funder types: Other

Identifiers

NCT02728700

IRB-34973

NCI-2016-00387 (Registry Identifier)

PEDSBMT295 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1 patient

Sex: All

Ages: 3 to 30 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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1 participants in 1 patient group

Treatment (sirolimus, HSCT, MMF)

Experimental group

Description:

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.

Treatment:

Drug: Sirolimus

Other: Laboratory Biomarker Analysis

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation

Drug: Mycophenolate Mofetil