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Sirolimus, Tacrolimus, Thymoglobulin and Rituximab as Graft-versus-Host-Disease Prophylaxis in Patients Undergoing Haploidentical and HLA Partially Matched Donor Hematopoietic Cell Transplantation

Information source: Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Chronic Myeloproliferative Disorders; Graft Versus Host Disease; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms

Intervention: anti-thymocyte globulin (Biological); rituximab (Biological); sirolimus (Drug); tacrolimus (Drug); laboratory biomarker analysis (Other); allogeneic hematopoietic stem cell transplantation (Procedure); management of therapy complications (Procedure); peripheral blood stem cell transplantation (Procedure)

Phase: Phase 2

Status: Terminated

Sponsored by: Barbara Ann Karmanos Cancer Institute

Official(s) and/or principal investigator(s):
Zaid Al-Kadhimi, M.D., Principal Investigator, Affiliation: Barbara Ann Karmanos Cancer Institute


This Phase II clinical trial was designed for patients with hematologic malignancies in need of donor peripheral blood stem cell transplant, and have no HLA matched donor. Therefore It will test the efficacy of combining sirolimus, tacrolimus, antithymocyte globulin, and rituximab in preventing graft versus host disease in transplants from HLA Haploidentical and partially mismatched donors.

Clinical Details

Official title: A Pilot Phase II Study of Sirolimus, Tacrolimus, Thymoglobulin and Rituximab as Graft-versus-Host-Disease Prophylaxis in Patients Undergoing Haploidentical and HLA Partially Matched Donor Hematopoietic Cell Transplantation

Study design: Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Primary outcome:

Incidence and Severity of Acute Graft-vs-host Disease (GVHD)

Time to Engraftment

Safety Assessment

Secondary outcome:

Incidence of Chronic GVHD

Incidence of Infections Including Cytomegalovirus, Epstein-Barr Virus Reactivation, and Post-transplant Lymphoproliferative Disorder

Incidence of Thrombotic Microangiopathy

Overall and Disease-free Survival

Immunocorrelative Studies Pre- and Periodically Post-transplantation

Detailed description: OBJECTIVES: Primary

- Determine the incidence and severity of acute graft-vs-host disease (GVHD) in patients

with hematologic malignancies undergoing donor peripheral blood stem cell transplantation who are receiving sirolimus, tacrolimus, anti-thymocyte globulin, and rituximab as GVHD prophylaxis.

- Assess time to engraftment absolute neutrophil count (> 0. 5 x 10^9/L for 3 consecutive

days) and platelet count (> 20 x 10^9/L for 3 consecutive days) in these patients.

- Determine the safety, as defined by serious adverse events and adverse events related

to this immunosuppressive regimen, in the first 6 months after treatment. Secondary

- Assess the incidence of chronic GVHD measured within 2 years after transplantation.

- Assess overall and disease-free survival at 2 years after transplantation.

- Examine the incidence of opportunistic infections including fungal infections,

pneumocystis carinii pneumonia, and viral infections (cytomegalovirus, varicella zoster virus, herpes simplex virus, BK virus, Epstein-Barr virus, and post-transplant lymphoproliferative disorder).

- Assess the incidence of thrombotic microangiopathy within 100 days of transplantation.

- Perform immunocorrelative studies, including T-cell, B-cell, NK-cell, regulatory cell,

and allo-reactive T-cell measurement studies via flow cytometry, at 30, 60, 90, and 180 days after transplantation.

OUTLINE: Patients receive rituximab IV on days - 7 and 3, tacrolimus IV continuously (may

switch to orally when the patient is able to eat) and oral sirolimus beginning on day - 3,

and anti-thymocyte globulin IV over 6 hours on days - 3 to -1. Tacrolimus and sirolimus are

tapered at the discretion of the treating physician. All patients also receive a standard transplant-preparative regimen and undergo transplantation on day 0. Blood samples are collected before the preparative regimen and at 30, 60, 90, and 180 days after transplantation for correlative immunologic studies. After completion of study treatment, patients are followed up for 2 years.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.



- Diagnosis of a hematological malignancy, including:

- Non-Hodgkin lymphoma

- Hodgkin lymphoma

- Acute myeloid leukemia or acute lymphoblastic leukemia

- Myelodysplastic syndrome (treated or untreated)

- Chronic myelogenous leukemia

- Multiple myeloma

- Chronic lymphocytic leukemia

- Myelofibrosis and other myeloproliferative disorders

- No suitable related HLA-matched or unrelated HLA-matched (8/8 or 7/8 matched) donor

- Available suitable haploidentical or partial-matched unrelated donor (high-resolution

molecular HLA typing is mandatory for HLA Class I and II)

- No more than 4/8 HLA allele or antigen mismatch for a haploidentical-related

first-degree family member donor

- Only 6/8 or 5/8 allele or antigen match for an unrelated donor

- Scheduled to undergo peripheral blood stem cell transplantation

- Not receiving bone marrow or ex vivo engineered or processed graft (e. g., CD34+

enrichment, T-cell depletion)

- No documented uncontrolled CNS disease


- Karnofsky performance status (PS) 70-100%

- ECOG PS 0-2

- Serum bilirubin < 3 times upper limit of normal (ULN)

- ALT and AST < 3 times ULN

- Creatinine clearance > 60 mL/min

- Ejection fraction > 50%

- Forced vital capacity, FEV_1, or DLCO > 50% predicted

- Negative pregnancy test

- Able to cooperate with oral medication intake

- Patients with coronary heart disease (recent myocardial infarctions, angina, cardiac

stent, or bypass surgery in the past 6 months) are eligible provided they are cleared with a stress echo or nuclear myocardial perfusions stress test and a cardiology consult

- No ascites

- No HIV positivity

- No active hepatitis B or C virus infection

- No known contraindication to the administration of sirolimus, tacrolimus,

anti-thymocyte globulin, or rituximab PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Not on home oxygen

Locations and Contacts

Karmanos Cancer Institute, Detroit, Michigan 48201, United States
Additional Information

Starting date: August 2010
Last updated: October 22, 2013

Page last updated: August 23, 2015

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