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

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

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.

Study Overview

• Status: Completed
• Conditions: Hematological Malignancies
• Intervention / Treatment: Drug: Tacrolimus and Thymoglobulin

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Tacrolimus and Thymoglobulin; Tacrolimus and Thymoglobulin, as Graft-versus-Host-Disease Prophylaxis

Drug: Tacrolimus and Thymoglobulin; 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.; Other Names: PROGRAF®

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Barbara Ann Karmanos Cancer Institute

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: November 21, 2010
• First Submitted That Met QC Criteria: November 22, 2010
• First Posted (Estimate): November 23, 2010

Study Record Updates

• Last Update Posted (Actual): June 18, 2018
• Last Update Submitted That Met QC Criteria: May 16, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: ● 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
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus; Thymoglobulin
• Other Study ID Numbers: WSU 2009-095