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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2016-00387 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| PEDSBMT295 | Other Identifier | OnCore |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Allogeneic Hematopoietic Stem Cell Transplantation | Procedure | Undergo HSCT |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of thrombotic microangiopathy defined according to the bone marrow transplant clinical trials network toxicity committee | 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. |
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Inclusion Criteria:
Subjects must have one of the following disease categories:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Rajni Agarwal-Hashmi | Stanford Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University, School of Medicine | Palo Alto | California | 94304 | United States |
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| Laboratory Biomarker Analysis | Other | Correlative studies |
|
| Mycophenolate Mofetil | Drug | Given IV |
|
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| Sirolimus | Drug | Given PO |
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| Up to 100 days |
| Incidence of venous-occlusive disease (VOD) using Modified Seattle Criteria | 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. | Up to 100 days |
| Severity of mucositis determined by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 | 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. | 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 | 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. | 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 | 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. | Baseline to up to 100 days |
| ID | Term |
|---|---|
| D006689 | Hodgkin Disease |
| D000754 | Anemia, Refractory, with Excess of Blasts |
| D001752 | Blast Crisis |
| D015466 | Leukemia, Myeloid, Chronic-Phase |
| D055728 | Primary Myelofibrosis |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D015470 | Leukemia, Myeloid, Acute |
| D008228 | Lymphoma, Non-Hodgkin |
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D000753 | Anemia, Refractory |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D009190 | Myelodysplastic Syndromes |
| D001855 | Bone Marrow Diseases |
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D002471 | Cell Transformation, Neoplastic |
| D063646 | Carcinogenesis |
| D009385 | Neoplastic Processes |
| D009196 | Myeloproliferative Disorders |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007945 | Leukemia, Lymphoid |
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| ID | Term |
|---|---|
| D009173 | Mycophenolic Acid |
| D020123 | Sirolimus |
| ID | Term |
|---|---|
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D018942 | Macrolides |
| D007783 | Lactones |
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