NCT01116232 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE2
Status at capture: TERMINATED
Registry last update: 2019-03-26

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

Time to Engraftment

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outcome · POSTED

Safety Assessment

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outcome · POSTED

Incidence of Chronic GVHD

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outcome · POSTED

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

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outcome · POSTED

Incidence of Thrombotic Microangiopathy

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outcome · POSTED

Overall and Disease-free Survival

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outcome · POSTED

Immunocorrelative Studies Pre- and Periodically Post-transplantation

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: DISEASE CHARACTERISTICS: * 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 PATIENT CHARACTERISTICS: * 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
healthy Volunteers: false
maximum Age: 120 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
anti-thymocyte globulin: Infuse the first dose over a minimum of 6 hours, and subsequent doses over a minimum of 4 hours via a 0.22 micron in-line filter Rituximab: The total dose chosen for this protocol is 28 mg/kg divided in two doses (14 mg/kg on days -7 and +3). Initial infusion: Start rate of 50 mg/hour; For adults, Sirolimus will be administered at 12 mg orally loading dose on day -3, followed by 4 mg orally single morning daily dose (target serum level 3-12 ng/ml by HPLC). Tacrolimus will be administered intravenously at a dose of 0.03 mg/kg (ideal body weight) q 24h by continuous infusion starting on Day -3. Intravenous Tacrolimus will be discontinued once the patient starts eating and the drug will then be given orally at a dose of approximately 4 times the intravenous dose.
intervention Names
Biological: anti-thymocyte globulin
Biological: rituximab
Drug: sirolimus
Drug: tacrolimus
Other: laboratory biomarker analysis
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: management of therapy complications
Procedure: peripheral blood stem cell transplantation
label
anti-thymocyte globulin, rituximab, sirolimus, tacrolimus,
type
EXPERIMENTAL

interventions

arm Group Labels
anti-thymocyte globulin, rituximab, sirolimus, tacrolimus,
description
Infuse the first dose over a minimum of 6 hours, and subsequent doses over a minimum of 4 hours via a 0.22 micron in-line filter.
name
anti-thymocyte globulin
type
BIOLOGICAL
arm Group Labels
anti-thymocyte globulin, rituximab, sirolimus, tacrolimus,
description
The total dose chosen for this protocol is 28 mg/kg divided in two doses (14 mg/kg on days -7 and +3). Initial infusion: Start rate of 50 mg/hour; if there is no reaction, increase the rate by 50 mg/hour increments every 30 minutes, to a maximum rate of 400 mg/hour. Subsequent infusions: If patient did not tolerate initial infusion follow initial infusion guidelines. If patient tolerated initial infusion, start at 100 mg/hour; if there is no reaction, increase the rate by 100 mg/hour increments every 30 minutes, to a maximum rate of 400 mg/hour. Note: If a reaction occurs, slow or stop the infusion. If the reaction abates, restart infusion at 50% of the previous rate. In patients who tolerated the Rituximab well in the past, a rapid infusion rate can be used over 90 minutes with 20% of the dose administered in the first 30 minutes and the remaining 80% is given over 60 minutes.
name
rituximab
other Names
Rituxan®
type
BIOLOGICAL
arm Group Labels
anti-thymocyte globulin, rituximab, sirolimus, tacrolimus,
description
For adults, Sirolimus will be administered at 12 mg orally loading dose on day -3, followed by 4 mg orally single morning daily dose (target serum level 3-12 ng/ml by HPLC).
name
sirolimus
other Names
Rapamune®
type
DRUG
arm Group Labels
anti-thymocyte globulin, rituximab, sirolimus, tacrolimus,
description
Tacrolimus will be administered intravenously at a dose of 0.03 mg/kg (ideal body weight) q 24h by continuous infusion starting on Day -3. Intravenous Tacrolimus will be discontinued once the patient starts eating and the drug will then be given orally at a dose of approximately 4 times the intravenous dose.
name
tacrolimus
other Names
Prograf
type
DRUG
arm Group Labels
anti-thymocyte globulin, rituximab, sirolimus, tacrolimus,
description
laboratory biomarker analysis
name
laboratory biomarker analysis
type
OTHER
arm Group Labels
anti-thymocyte globulin, rituximab, sirolimus, tacrolimus,
description
allogeneic hematopoietic stem cell transplantation
name
allogeneic hematopoietic stem cell transplantation
type
PROCEDURE
arm Group Labels
anti-thymocyte globulin, rituximab, sirolimus, tacrolimus,
description
management of therapy complications
name
management of therapy complications
type
PROCEDURE
arm Group Labels
anti-thymocyte globulin, rituximab, sirolimus, tacrolimus,
description
peripheral blood stem cell transplantation
name
peripheral blood stem cell transplantation
type
PROCEDURE

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

SUPPORTIVE_CARE

Enrollment

count: 4
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

measure
Incidence and Severity of Acute Graft-vs-host Disease (GVHD)
time Frame
During the first six months post transplant
measure
Time to Engraftment
time Frame
During the first six months post transplant
measure
Safety Assessment
time Frame
During the first six months post transplant

secondary Outcomes

measure
Incidence of Chronic GVHD
time Frame
Within two years after transplant
measure
Incidence of Infections Including Cytomegalovirus, Epstein-Barr Virus Reactivation, and Post-transplant Lymphoproliferative Disorder
time Frame
At one year
measure
Incidence of Thrombotic Microangiopathy
time Frame
Within 100 days of HCT
measure
Overall and Disease-free Survival
time Frame
At 1 year
measure
Immunocorrelative Studies Pre- and Periodically Post-transplantation
time Frame
Using flow cytometry at 30, 60, 90, and 180 days post transplant.

Full study description

brief Summary: 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.
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.

Source references