免费获得国外相关药品，最快 1 个工作日回馈药物信息
出境医 / 临床实验 / Sirolimus and Mycophenolate Mofetil in Preventing GVHD in Patients With Hematologic Malignancies Undergoing HSCT
Sirolimus and Mycophenolate Mofetil in Preventing GVHD in Patients With Hematologic Malignancies Undergoing HSCT
Study Description
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| 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 | Procedure: Allogeneic Hematopoietic Stem Cell Transplantation Other: Laboratory Biomarker Analysis Drug: Mycophenolate Mofetil Drug: Sirolimus | Phase 1 |
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.
Study Design
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 1 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Prevention |
| 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 Start Date : | February 2016 |
| Actual Primary Completion Date : | April 2017 |
| Actual Study Completion Date : | July 2018 |
Arms and Interventions
| Arm | Intervention/treatment |
|---|---|
|
Experimental: 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.
|
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo HSCT
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies
Drug: Mycophenolate Mofetil Given IV
Other Names:
Drug: Sirolimus Given PO
Other Names:
|
Outcome Measures
Primary Outcome Measures :
- Incidence of acute GvHD grade 3 & 4, according to the Glucksberg staging criteria [ Time Frame: Up to 60 days post-transplant ]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.
- Incidence of acute GvHD grade 3 & 4, according to the Glucksberg staging criteria [ Time Frame: Up to 100 days post-transplant ]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.
Secondary Outcome Measures :
- Incidence of thrombotic microangiopathy defined according to the bone marrow transplant clinical trials network toxicity committee [ Time Frame: Up to 100 days ]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.
- Incidence of venous-occlusive disease (VOD) using Modified Seattle Criteria [ Time Frame: Up to 100 days ]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.
- Severity of mucositis determined by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 [ Time Frame: Up to 100 days ]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.
- Time to neutrophil engraftment defined as first of 3 consecutive days with the absolute neutrophil count is > 500/ul in the peripheral blood [ Time Frame: Baseline to up to 100 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.
- 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 [ Time Frame: Baseline to up to 100 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.
Eligibility Criteria
| Ages Eligible for Study: | 3 Years to 30 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Locations
| United States, California | |
| Stanford University, School of Medicine | |
| Palo Alto, California, United States, 94304 | |
Sponsors and Collaborators
Stanford University
Investigators
| Principal Investigator: | Rajni Agarwal-Hashmi | Stanford Cancer Institute |
| Tracking Information | |||||||
|---|---|---|---|---|---|---|---|
| First Submitted Date ICMJE | March 30, 2016 | ||||||
| First Posted Date ICMJE | April 5, 2016 | ||||||
| Last Update Posted Date | September 12, 2018 | ||||||
| Study Start Date ICMJE | February 2016 | ||||||
| Actual Primary Completion Date | April 2017 (Final data collection date for primary outcome measure) | ||||||
| Current Primary Outcome Measures ICMJE |
|
||||||
| Original Primary Outcome Measures ICMJE | Same as current | ||||||
| Change History | |||||||
| Current Secondary Outcome Measures ICMJE |
|
||||||
| Original Secondary Outcome Measures ICMJE | Same as current | ||||||
| Current Other Pre-specified Outcome Measures | Not Provided | ||||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||||
| Descriptive Information | |||||||
| Brief Title ICMJE | Sirolimus and Mycophenolate Mofetil in Preventing GVHD in Patients With Hematologic Malignancies Undergoing HSCT | ||||||
| Official Title ICMJE | 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 | ||||||
| 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. |
||||||
| Study Type ICMJE | Interventional | ||||||
| Study Phase ICMJE | Phase 1 | ||||||
| Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Prevention |
||||||
| Condition ICMJE |
|
||||||
| Intervention ICMJE |
|
||||||
| Study Arms ICMJE | Experimental: 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.
Interventions:
|
||||||
| Publications * | Not Provided | ||||||
|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||||
| Recruitment Information | |||||||
| Recruitment Status ICMJE | Terminated | ||||||
| Actual Enrollment ICMJE |
1 | ||||||
| Original Estimated Enrollment ICMJE |
9 | ||||||
| Actual Study Completion Date ICMJE | July 2018 | ||||||
| Actual Primary Completion Date | April 2017 (Final data collection date for primary outcome measure) | ||||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
|
||||||
| Sex/Gender ICMJE |
|
||||||
| Ages ICMJE | 3 Years to 30 Years (Child, Adult) | ||||||
| Accepts Healthy Volunteers ICMJE | No | ||||||
| Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
| Listed Location Countries ICMJE | United States | ||||||
| Removed Location Countries | |||||||
| Administrative Information | |||||||
| NCT Number ICMJE | NCT02728700 | ||||||
| Other Study ID Numbers ICMJE | IRB-34973 NCI-2016-00387 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) PEDSBMT295 ( Other Identifier: OnCore ) |
||||||
| Has Data Monitoring Committee | Yes | ||||||
| U.S. FDA-regulated Product |
|
||||||
| IPD Sharing Statement ICMJE |
|
||||||
| Responsible Party | Stanford University | ||||||
| Study Sponsor ICMJE | Stanford University | ||||||
| Collaborators ICMJE | Not Provided | ||||||
| Investigators ICMJE |
|
||||||
| PRS Account | Stanford University | ||||||
| Verification Date | August 2018 | ||||||
|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
|||||||
