NCT00691015 · REGISTRY CONDITION SEARCH

Sirolimus, Tacrolimus, and Antithymocyte Globulin in Preventing Graft-Versus-Host Disease in Patients With Hematologic Cancer Who Are Undergoing Donor Stem Cell Transplant

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: COMPLETED
Registry last update: 2017-06-28

RATIONALE: Giving low doses of chemotherapy, monoclonal antibodies, and radiation therapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus, sirolimus, and antithymocyte globulin before and after transplant may stop this from happening. PURPOSE: This phase II trial is studying the side effects of giving sirolimus together with tacrolimus and antithymocyte globulin and to see how well it works in preventing graft-versus-host disease in patients with hematologic cancer who are undergoing donor stem cell transplant.

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 of Acute Graft-versus-host Disease (GVHD)

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outcome · POSTED

Severity of Acute Graft-versus-host Disease (GVHD)

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outcome · POSTED

Safety, as Defined by Serious Adverse Events and Adverse Events Related to Study Treatment.

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outcome · POSTED

Incidence of Chronic GVHD.

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outcome · POSTED

Time to Engraftment (i.e., Absolute Neutrophil Recovery [ANC > 500/mm³] )

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outcome · POSTED

Overall Survival.

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outcome · POSTED

Incidence of Infections, Including Bacterial, Fungal, and Viral Infections (i.e., CMV and EBV Reactivation, Including Post-transplant Lymphoproliferative Disorders)

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outcome · POSTED

Karnofsky Performance Status Performance Status

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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 any of the following: * Non-Hodgkin lymphoma in complete remission (CR) or partial remission (PR) * Hodgkin lymphoma in CR or PR * Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) meeting either of the following criteria: * In CR * Not in CR and meets the following criteria: * Bone marrow blast \< 20% within 4 weeks of transplantation * Peripheral blood absolute blast count \< 500 per microliter on the day of initiating conditioning therapy * Myelodysplastic syndromes, treated or untreated * Chronic myeloid leukemia in chronic phase or accelerated phase * Multiple myeloma in CR or PR * Chronic lymphocytic leukemia in second or greater CR or PR * Myelofibrosis or other myeloproliferative disorders meeting the following criteria: * Bone marrow blasts \< 20% within 4 weeks of transplantation * Peripheral blood absolute blast count \< 500 per microliter on the day of initiating conditioning therapy * Patients with ascites not allowed * No prior bone marrow or ex vivo engineered or processed graft (i.e., CD34+ enrichment, T-cell depletion, etc) * Scheduled to undergo peripheral blood stem cell transplantation from a suitable HLA-matched or -mismatched unrelated donor, as determined by treating physician * High resolution molecular HLA typing is required for HLA class I and II * No more than one antigen or allele mismatch * No documented uncontrolled CNS disease PATIENT CHARACTERISTICS: * ECOG performance status (PS) 0-2 * Karnofsky PS 60-100% * Creatinine clearance \> 50 mL/min * Bilirubin \< 3 times upper limit of normal (ULN) * ALT and AST \< 3 times ULN * LVEF \> 50% * FVC, FEV\_1, or DLCO \> 50% predicted * Patients on home oxygen not allowed * Able to cooperate with oral medication intake * HIV negative * No active hepatitis B or hepatitis C * No known contraindication to sirolimus, tacrolimus, or anti-thymocyte globulin PRIOR CONCURRENT THERAPY: * See Disease Characteristics
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Standard of care (SOC) chemotherapy or ( SOC) chemotherapy + total body irradiation (TBI) of one of the following regimens: Regimen I: Patients receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV;anti-thymocyte globulin IV. Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV; anti-thymocyte globulin IV. Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV; anti-thymocyte globulin IV. Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI; anti-thymocyte globulin IV.
intervention Names
Biological: rituximab
Drug: busulfan
Drug: carmustine
Drug: cyclophosphamide
Drug: cytarabine
Drug: etoposide
Drug: fludarabine phosphate
Drug: melphalan
Radiation: total body irradiation (TBI)
Drug: anti-thymocyte globulin IV
label
Chemotherapy or chemotherapy + total body irradiation
type
EXPERIMENTAL

interventions

arm Group Labels
Chemotherapy or chemotherapy + total body irradiation
description
Given IV
name
rituximab
other Names
Rituxan
MabThera
Zytux
type
BIOLOGICAL
arm Group Labels
Chemotherapy or chemotherapy + total body irradiation
description
Given IV
name
busulfan
other Names
Busulfex
Myleran
type
DRUG
arm Group Labels
Chemotherapy or chemotherapy + total body irradiation
description
Given IV
name
carmustine
other Names
Bicnu
Gliadel
type
DRUG
arm Group Labels
Chemotherapy or chemotherapy + total body irradiation
description
Given IV
name
cyclophosphamide
other Names
Cytoxan
Cytoxan Lyophilized
Neosar
type
DRUG
arm Group Labels
Chemotherapy or chemotherapy + total body irradiation
description
Given IV
name
cytarabine
other Names
Depocyt
type
DRUG
arm Group Labels
Chemotherapy or chemotherapy + total body irradiation
description
Given IV
name
etoposide
other Names
Etopophos
Toposar
type
DRUG
arm Group Labels
Chemotherapy or chemotherapy + total body irradiation
description
Given IV
name
fludarabine phosphate
other Names
Fludara®
type
DRUG
arm Group Labels
Chemotherapy or chemotherapy + total body irradiation
description
Given IV
name
melphalan
other Names
Alkeran
type
DRUG
arm Group Labels
Chemotherapy or chemotherapy + total body irradiation
description
Given once or twice daily
name
total body irradiation (TBI)
other Names
radiotherapy
type
RADIATION
arm Group Labels
Chemotherapy or chemotherapy + total body irradiation
description
Given IV
name
anti-thymocyte globulin IV
other Names
Thymoglobulin
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

SUPPORTIVE_CARE

Enrollment

count: 48
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

measure
Incidence of Acute Graft-versus-host Disease (GVHD)
time Frame
Within 100 days after donor peripheral blood stem cell transplantation (PBSCT) as assessed by Glucksberg criteria
measure
Severity of Acute Graft-versus-host Disease (GVHD)
time Frame
Within 100 days after donor peripheral blood stem cell transplantation (PBSCT) as assessed by Glucksberg criteria
measure
Safety, as Defined by Serious Adverse Events and Adverse Events Related to Study Treatment.
time Frame
Within 6 months after PBSCT

secondary Outcomes

measure
Incidence of Chronic GVHD.
time Frame
Within 2 years after PBSCT
measure
Time to Engraftment (i.e., Absolute Neutrophil Recovery [ANC > 500/mm³] )
time Frame
post transplant, up to 4 weeks
measure
Overall Survival.
time Frame
At 2 years after PBSCT
measure
Incidence of Infections, Including Bacterial, Fungal, and Viral Infections (i.e., CMV and EBV Reactivation, Including Post-transplant Lymphoproliferative Disorders)
time Frame
Within 6 months after PBSCT
description
100 - Normal; no complaints; no evidence of disease. 90 - Able to carry on normal activity; minor signs or symptoms of disease. 80 - Normal activity with effort; some signs or symptoms of disease. 70 - Cares for self; unable to carry on normal activity or to do active work. 60 - Requires occasional assistance, but is able to care for most of their personal needs. 50 - Requires considerable assistance and frequent medical care. 40 - Disabled; requires special care and assistance. 30 - Severely disabled; hospital admission is indicated although death not imminent. 20 - Very sick; hospital admission necessary; active supportive treatment necessary. 10 - Moribund; fatal processes progressing rapidly. 0 - Dead
measure
Karnofsky Performance Status Performance Status
time Frame
At 90 days after PBSCT

Full study description

brief Summary: RATIONALE: Giving low doses of chemotherapy, monoclonal antibodies, and radiation therapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus, sirolimus, and antithymocyte globulin before and after transplant may stop this from happening. PURPOSE: This phase II trial is studying the side effects of giving sirolimus together with tacrolimus and antithymocyte globulin and to see how well it works in preventing graft-versus-host disease in patients with hematologic cancer who are undergoing donor stem cell transplant.
detailed Description: OBJECTIVES: Primary * To determine the incidence and severity of acute graft-versus-host disease (GVHD) after HLA-matched or -mismatched unrelated donor peripheral blood stem cell transplantation (PBSCT) in patients with hematologic malignancies treated with immunosuppressive therapy comprising sirolimus, tacrolimus, and anti-thymocyte globulin as GVHD prophylaxis. * To determine the safety of this regimen in these patients at 6 months after PBSCT. Secondary * To determine the time to engraftment (i.e., platelet and absolute neutrophil recovery) in patients treated with this regimen. * To determine the length of hospital stay of these patients within 100 days after PBSCT. * To determine the incidence of infections, including CMV and EBV reactivation and post-transplant lymphoproliferative disorders, in patients treated with this regimen. * To determine the incidence of thrombotic microangiopathy and veno-occlusive disease in patients treated with this regimen. * To determine the incidence of chronic GVHD in patients treated with this regimen. * To determine the overall and disease-free survival of these patients at 2 years after PBSCT. * To determine the Karnofsky performance status of these patients at baseline and at various time points after PBSCT. * To conduct immunocorrelative studies prior to and at various time points after PBSCT. OUTLINE: * Conditioning regimen: Patients receive 1 of 6 conditioning regimens (standard of care treatment) between days -9 and -3, based on diagnosis and the treating physician's preference regarding regimen intensity. * Regimen I: Patients receive fludarabine phosphate IV and busulfan IV. * Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV. * Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV. * Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV. * Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV. * Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI. * Allogeneic peripheral blood stem cell transplantation: Patients undergo filgrastim (G-CSF)-mobilized allogeneic peripheral blood stem cell transplantation on day 0. * Graft-versus-host disease prophylaxis (GVHD): Patients receive tacrolimus IV continuously over 24 hours or orally and sirolimus orally beginning on day -3 and continuing until day 30 or day 90, followed by a taper in the absence of GVHD. Patients also receive anti-thymocyte globulin IV over 4-8 hours on days -3 to -1. Blood samples are obtained at baseline and periodically during study for correlative biomarker studies. Samples are analyzed by T-cell immunophenotyping, absolute subset number quantification, and multi-parameter flow cytometry for evaluation of immune reconstitution, T-cell differentiation status, NK-cell recovery, allo-reactivity of donor T-cells after transplantation, and regulatory T-cell reconstitution. After completion of study therapy, patients are followed periodically for up to 2 years.

Source references

Source notices and limitations

Discovery and provenance

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Preserved source evidence · Not medical advice