Tacrolimus and Thymoglobulin, as GvHD Prophylaxis in Patients Undergoing Related Donor HCT

Study Overview
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Brief Summary
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The primary goal of the study is to determine the incidence and severity of acute Graft versus Host Disease (GVHD) following human leukocyte antigen (HLA) matched related donor Hematopoetic Stem Cell(HSC) transplant in patients with blood related cancers who receive the combination of tacrolimus and Thymoglobulin as GVHD prophylaxis. The investigators also will determine the safety of this combination in the first six months post transplant. Secondary goals include determining the time to recovery of white blood cells and platelets (engraftment), determining the occurrence of opportunistic infections, defined as infection that occurs in people with weakened immune systems and caused by organisms that do not normally cause disease (fungal infections, pneumocystis carinii pneumonia (PCP), and viral infections), estimating the incidence of chronic GVHD at two years and the overall and disease free survival at two years. Immune response will be assessed by means of immuno-correlative studies both prior to and at various points after transplant.

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

Conditions
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Hematological Malignancies

Intervention / Treatment
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* Drug: Tacrolimus and Thymoglobulin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tacrolimus and Thymoglobulin<br>Tacrolimus and Thymoglobulin, as Graft-versus-Host-Disease Prophylaxis | Drug: Tacrolimus and Thymoglobulin<br>* Intravenous Tacrolimus 0.03 mg/kg/d, beginning day -3, where day 0 is the day of stem cell infusion or transplant. Intravenous tacrolimus will be discontinued once the participant starts eating, and the drug will then be given orally at a dose of approximately 4 times the intravenous dose. Tacrolimus will be discontinued starting 100 days after transplant unless signs of acute and chronic GVHD develop or if severe toxicity occurs. Thymoglobulin will be given 0.5 mg/kg day-3, Thymoglobulin 1.5 mg/kg day -2, Thymoglobulin 2.5 mg/kg day -1. Thymoglobulin will be given intravenously over 6 hours.<br>* Other names: PROGRAF®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Acute GVHD | Cumulative Incidence of grade II-V acute GVHD with relapse or NRM as competing risks | Assessed first 6 months post transplant | 
| Safety Defined by Serious Adverse Events | Counted the number of participants that experienced any type of grade 3 or higher toxicity. | Assessed first 6 months post transplant | 
| Severity of Acute GVHD | Cumulative Incidence of grade III-V acute GVHD with relapse or NRM as competing risks | Assessed first 6 months post transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine Incidence of Opportunistic Infections |  | Followed for up to two years post transplant | 
| Estimate Incidence of Chronic GVHD at Two Years | Cumulative Incidence of chronic GVHD with relapse or NRM as competing risks | Followed for up to two years post transplant | 
| Overall Survival at Two Year, |  | Followed for up to two years post transplant | 
| Determine Time to Engraftment (G500) | The number of days until engraftment (G500) | Followed for up to two years post transplant | 
| Determine Time to Engraftment (PLT20) | The number of days until engraftment (PLT20) | Followed for up to two years post transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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● Non-Hodgkin lymphoma,, ● Hodgkin disease,, ● Acute Myelogenous or Acute Lymphocytic Leukemia, ● Myelodysplastic Syndromes,, ● Chronic Myelogenous Leukemia, ● Multiple Myeloma, ● Chronic Lymphocytic Leukemia, ● Myelofibrosis and other myeloproliferative disorders;