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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


Phase 2
18 Years
N/A
Not Enrolling
Both
Chronic Myeloproliferative Disorders, Graft Versus Host Disease, Leukemia, Lymphoma, Lymphoproliferative Disorder, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms

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Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Incidence and severity of acute graft-vs-host disease (GVHD)

Outcome Time Frame:

During the first six months post transplant

Safety Issue:

No

Principal Investigator

Zaid Al-Kadhimi, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Barbara Ann Karmanos Cancer Institute

Authority:

United States: Institutional Review Board

Study ID:

CDR0000671822

NCT ID:

NCT01116232

Start Date:

August 2010

Completion Date:

Related Keywords:

  • Chronic Myeloproliferative Disorders
  • Graft Versus Host Disease
  • Leukemia
  • Lymphoma
  • Lymphoproliferative Disorder
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Neoplasms
  • graft versus host disease
  • accelerated phase chronic myelogenous leukemia
  • adult acute lymphoblastic leukemia in remission
  • adult acute myeloid leukemia in remission
  • adult acute myeloid leukemia with 11q23 (MLL) abnormalities
  • adult acute myeloid leukemia with inv(16)(p13;q22)
  • adult acute myeloid leukemia with t(15;17)(q22;q12)
  • adult acute myeloid leukemia with t(16;16)(p13;q22)
  • adult acute myeloid leukemia with t(8;21)(q22;q22)
  • atypical chronic myeloid leukemia, BCR-ABL negative
  • blastic phase chronic myelogenous leukemia
  • chronic myelomonocytic leukemia
  • chronic phase chronic myelogenous leukemia
  • meningeal chronic myelogenous leukemia
  • progressive hairy cell leukemia, initial treatment
  • prolymphocytic leukemia
  • recurrent adult acute lymphoblastic leukemia
  • recurrent adult acute myeloid leukemia
  • recurrent adult T-cell leukemia/lymphoma
  • refractory chronic lymphocytic leukemia
  • refractory hairy cell leukemia
  • relapsing chronic myelogenous leukemia
  • stage I adult T-cell leukemia/lymphoma
  • stage I chronic lymphocytic leukemia
  • stage II adult T-cell leukemia/lymphoma
  • stage II chronic lymphocytic leukemia
  • stage III adult T-cell leukemia/lymphoma
  • stage III chronic lymphocytic leukemia
  • stage IV adult T-cell leukemia/lymphoma
  • stage IV chronic lymphocytic leukemia
  • T-cell large granular lymphocyte leukemia
  • untreated adult acute lymphoblastic leukemia
  • untreated adult acute myeloid leukemia
  • untreated hairy cell leukemia
  • recurrent adult Hodgkin lymphoma
  • stage I adult Hodgkin lymphoma
  • stage II adult Hodgkin lymphoma
  • stage III adult Hodgkin lymphoma
  • stage IV adult Hodgkin lymphoma
  • anaplastic large cell lymphoma
  • angioimmunoblastic T-cell lymphoma
  • cutaneous B-cell non-Hodgkin lymphoma
  • recurrent cutaneous T-cell non-Hodgkin lymphoma
  • stage I cutaneous T-cell non-Hodgkin lymphoma
  • stage II cutaneous T-cell non-Hodgkin lymphoma
  • stage III cutaneous T-cell non-Hodgkin lymphoma
  • stage IV cutaneous T-cell non-Hodgkin lymphoma
  • recurrent mycosis fungoides/Sezary syndrome
  • stage I mycosis fungoides/Sezary syndrome
  • stage II mycosis fungoides/Sezary syndrome
  • stage III mycosis fungoides/Sezary syndrome
  • stage IV mycosis fungoides/Sezary syndrome
  • adult grade III lymphomatoid granulomatosis
  • adult nasal type extranodal NK/T-cell lymphoma
  • Waldenstrom macroglobulinemia
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone lymphoma
  • contiguous stage II adult Burkitt lymphoma
  • contiguous stage II adult diffuse large cell lymphoma
  • contiguous stage II adult diffuse mixed cell lymphoma
  • contiguous stage II adult diffuse small cleaved cell lymphoma
  • contiguous stage II adult immunoblastic large cell lymphoma
  • contiguous stage II adult lymphoblastic lymphoma
  • contiguous stage II grade 1 follicular lymphoma
  • contiguous stage II grade 2 follicular lymphoma
  • contiguous stage II grade 3 follicular lymphoma
  • contiguous stage II mantle cell lymphoma
  • contiguous stage II marginal zone lymphoma
  • contiguous stage II small lymphocytic lymphoma
  • stage I adult Burkitt lymphoma
  • stage I adult diffuse large cell lymphoma
  • stage I adult diffuse mixed cell lymphoma
  • stage I adult diffuse small cleaved cell lymphoma
  • stage I adult immunoblastic large cell lymphoma
  • stage I adult lymphoblastic lymphoma
  • stage I grade 1 follicular lymphoma
  • stage I grade 2 follicular lymphoma
  • stage I grade 3 follicular lymphoma
  • stage I mantle cell lymphoma
  • stage I marginal zone lymphoma
  • stage I small lymphocytic lymphoma
  • noncontiguous stage II adult Burkitt lymphoma
  • noncontiguous stage II adult diffuse large cell lymphoma
  • noncontiguous stage II adult diffuse mixed cell lymphoma
  • noncontiguous stage II adult diffuse small cleaved cell lymphoma
  • noncontiguous stage II adult immunoblastic large cell lymphoma
  • noncontiguous stage II adult lymphoblastic lymphoma
  • noncontiguous stage II grade 1 follicular lymphoma
  • noncontiguous stage II grade 2 follicular lymphoma
  • noncontiguous stage II grade 3 follicular lymphoma
  • noncontiguous stage II mantle cell lymphoma
  • noncontiguous stage II marginal zone lymphoma
  • noncontiguous stage II small lymphocytic lymphoma
  • stage III adult Burkitt lymphoma
  • stage III adult diffuse large cell lymphoma
  • stage III adult diffuse mixed cell lymphoma
  • stage III adult diffuse small cleaved cell lymphoma
  • stage III adult immunoblastic large cell lymphoma
  • stage III adult lymphoblastic lymphoma
  • stage III grade 1 follicular lymphoma
  • stage III grade 2 follicular lymphoma
  • stage III grade 3 follicular lymphoma
  • stage III mantle cell lymphoma
  • stage III marginal zone lymphoma
  • stage III small lymphocytic lymphoma
  • stage IV adult Burkitt lymphoma
  • stage IV adult diffuse large cell lymphoma
  • stage IV adult diffuse mixed cell lymphoma
  • stage IV adult diffuse small cleaved cell lymphoma
  • stage IV adult immunoblastic large cell lymphoma
  • stage IV adult lymphoblastic lymphoma
  • stage IV grade 1 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • stage IV mantle cell lymphoma
  • stage IV marginal zone lymphoma
  • stage IV small lymphocytic lymphoma
  • recurrent adult Burkitt lymphoma
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • recurrent adult grade III lymphomatoid granulomatosis
  • recurrent adult immunoblastic large cell lymphoma
  • recurrent adult lymphoblastic lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent mantle cell lymphoma
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic lymphoma
  • intraocular lymphoma
  • post-transplant lymphoproliferative disorder
  • chronic eosinophilic leukemia
  • chronic neutrophilic leukemia
  • primary myelofibrosis
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • refractory multiple myeloma
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • myelodysplastic/myeloproliferative neoplasm, unclassifiable
  • Neoplasms
  • Graft vs Host Disease
  • Leukemia
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoproliferative Disorders
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Lymphoma, Large-Cell, Immunoblastic
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location

Karmanos Cancer InstituteDetroit, Michigan  48201