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Tacrolimus and ATG as GVHD Prophylaxis in Patients Undergoing Related Donor HSCT

Information source: Barbara Ann Karmanos Cancer Institute
Information obtained from ClinicalTrials.gov on February 07, 2013
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic 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); Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Stage II Adult Diffuse Small Cleaved Cell Lymphoma; 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; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell 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 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; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; 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 Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin 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 Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone 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 Hodgkin Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Adult T-cell Leukemia/Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Cutaneous T-cell Non-Hodgkin 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 Multiple Myeloma; Stage I Mycosis Fungoides/Sezary Syndrome; Stage I Small Lymphocytic Lymphoma; Stage II Adult Hodgkin Lymphoma; Stage II Adult T-cell Leukemia/Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Multiple Myeloma; Stage II Mycosis Fungoides/Sezary Syndrome; 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 Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Cutaneous T-cell Non-Hodgkin 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 Multiple Myeloma; Stage III Mycosis Fungoides/Sezary Syndrome; 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 Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Cutaneous T-cell Non-Hodgkin 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 Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenstrom Macroglobulinemia

Intervention: tacrolimus (Drug); anti-thymocyte globulin (Biological); laboratory biomarker analysis (Other); flow cytometry (Other); allogeneic hematopoietic stem cell transplantation (Procedure); peripheral blood stem cell transplantation (Procedure)

Phase: Phase 2

Status: Recruiting

Sponsored by: Barbara Ann Karmanos Cancer Institute

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

Summary

This phase II trial studies how well giving tacrolimus and anti-thymocyte globulin together works in preventing graft-vs-host disease (GVHD) in patients with hematologic malignancies undergoing donor peripheral blood stem cell transplant (PBSCT). Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving tacrolimus together with anti-thymocyte globulin may stop this from happening

Clinical Details

Official title: A Phase II Study of Tacrolimus and Thymoglobulin, as Graft-versus-Host-Disease Prophylaxis in Patients Undergoing Related Donor Hematopoietic Cell Transplantation

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Primary outcome:

Proportion of aGVHD graded according to the Glucksberg criteria

Safety of tacrolimus and anti-thymocyte globulin

Secondary outcome:

Proportion of chronic GVHD

Time to engraftment: time to neutrophil (> 500) and platelet (> 25K) count recovery

Overall and disease-free survival

Incidence of opportunistic infections, including fungal, and viral (CMV and EBV reactivation including PTLD)

Biomarkers and immunocorrelative studies

Detailed description: PRIMARY OBJECTIVES:

I. To determine the incidence and severity of acute GVHD (aGVHD) following human leukocyte antigen (HLA) matched related donor hematopoietic peripheral blood transplant in patients with hematologic malignancies that receive the immunosuppressive combination of Tacrolimus and Thymoglobulin (anti-thymocyte globulin) as GVHD prophylaxis.

II. To determine the safety of this combination in the first six months post transplant.

SECONDARY OBJECTIVES:

I. To determine engraftment time of neutrophils (absolute neutrophil count > 0. 5 x 10^9/L for 3 consecutive days), and platelets (platelet count > 20 X 10^9/L for 3 consecutive days).

II. To determine incidence of opportunistic infections, defined as infection that occurs in people with weakened immune systems and caused by an organism that does not normally cause disease. These include: fungal infections, pneumocytics carinii pneumonia (PCP), and viral infections (cytomegalovirus [CMV], varicella zoster virus [VZV], herpes simplex virus [HSV], BK virus [BK], Epstein-Barr virus [EBV], including post-transplant lymphoproliferative disorder [PTLD]).

III. To estimate incidence of chronic GVHD (cGVHD) at two years. IV. To determine overall and disease free survival at two years. V. To assess immune response with immunocorrelative studies both pre and at various points post transplant.

OUTLINE:

GVHD PROPHYLAXIS: Patients receive tacrolimus intravenously (IV) continuously or orally (PO)

on days - 3 to 60 with taper to day 100 (high-risk disease) or on days -3 to 100 with taper

to day 180 (low-risk disease). Patients also receive anti-thymocyte globulin IV over 4-6

hours on days - 3 to -1.

PREPARATIVE REGIMEN: Patients receive standard of care (at the Karmanos Cancer Institute) preparative regimens chosen by the treating physician, based on diagnosis.

TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0.

After completion of study treatment, patients are followed up for 2 years.

Eligibility

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Suitable related donor as determined by the treating physician

- High resolution molecular HLA typing is mandatory for HLA Class I and II

- Diagnosis of hematological malignancy

- Patients with one of the following hematologic malignancies, and felt to be

transplant candidates by their treating physician are eligible to enroll on this protocol:

- Non-Hodgkin lymphoma, any complete remission (CR)/partial remission (PR)

- Hodgkin disease, any CR/PR/stable disease (SD)

- Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) any CR; for non-CR

AML or ALL, bone marrow blast < 20% within 4 weeks of transplant and peripheral blood (PB) absolute blast count < 500/μl on the day of initiation of conditioning

- Myelodysplastic syndrome (MDS), treated or untreated

- Chronic myelogenous leukemia (CML) in chronic phase or accelerated phase

- Chronic myelomonocytic leukemia (CMML)

- Multiple myeloma, any CR/PR/SD

- Chronic lymphocytic leukemia (CLL) any CR/PR

- Myelofibrosis and other myeloproliferative disorders; bone marrow blasts less than 20

percent within four weeks of transplant and peripheral blood absolute blast counts less than 500 per microliter on the day of initiation of conditioning

- Age >= 18 and able to cooperate with oral medication intake

- Filgrastim (G-CSF) mobilized Peripheral blood stem cells

- Agrees to participate, and informed consent signed

- Karnofsky performance status (KPS) >= 60, Eastern Cooperative Oncology Group (ECOG)

performance status =< 2

- Creatinine clearance > 60 mL/min

- Ejection fraction > 50%

- Serum bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST)

less than 3 X upper limit of normal

- Forced vital capacity (FVC), forced expiratory volume in one second (FEV1) or

diffusion capacity of carbon monoxide (DLCO) > 50% predicted

Exclusion Criteria:

- Bone marrow or Ex vivo engineered or processed graft (cluster of differentiation

[CD]34+ enrichment, T-cell depletion, etc)

- Patients with documented uncontrolled central nervous system (CNS) disease

- Active donor or recipient serology positive for human immunodeficiency virus (HIV)

- Known contraindication to administration of Tacrolimus or Thymoglobulin

- Active Hepatitis B or C

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

stent, or bypass surgery in the last 6 months) need to be cleared with a stress echocardiogram or nuclear myocardial perfusion stress test, and cardiology consult; all other cardiac history will be at the discretion of the Principal Investigator

- Oxygen usage at the time of enrollment

- Patients with clinical ascites

- Women who are pregnant or nursing

Locations and Contacts

Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201, United States; Recruiting
Zaid S. Al-Kadhimi, Phone: 313-576-8022, Email: alkadhiz@karmanos.org
Zaid S. Al-Kadhimi, Principal Investigator
Joseph Uberti, M.D., Ph.D., Sub-Investigator
Lawrence G. Lum, M.D., DSc, Sub-Investigator
Voravit Ratanatharathorn, M.D., Sub-Investigator
Lois Ayash, M.D., Sub-Investigator
Muneer Abidi, M.D., Sub-Investigator
Abhinav Deol, M.D., Sub-Investigator
Additional Information

Starting date: November 2010
Last updated: April 30, 2012

Page last updated: February 07, 2013

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