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

Primary Purpose

Hematological Malignancies

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Tacrolimus and Thymoglobulin

About this trial

This is an interventional treatment trial for Hematological Malignancies focused on measuring ● 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;

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Barbara Ann Karmanos Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tacrolimus and Thymoglobulin

Arm Description

Tacrolimus and Thymoglobulin, as Graft-versus-Host-Disease Prophylaxis

Outcomes

Primary Outcome Measures

Incidence of Acute GVHD

Cumulative Incidence of grade II-V acute GVHD with relapse or NRM as competing risks

Safety Defined by Serious Adverse Events

Counted the number of participants that experienced any type of grade 3 or higher toxicity.

Severity of Acute GVHD

Cumulative Incidence of grade III-V acute GVHD with relapse or NRM as competing risks

Secondary Outcome Measures

Determine Incidence of Opportunistic Infections

Estimate Incidence of Chronic GVHD at Two Years

Cumulative Incidence of chronic GVHD with relapse or NRM as competing risks

Overall Survival at Two Year,

Determine Time to Engraftment ("G500")

The number of days until engraftment ("G500")

Determine Time to Engraftment ("PLT20")

The number of days until engraftment ("PLT20")

Full Information

NCT ID

NCT01246206

First Posted

November 21, 2010

Last Updated

May 16, 2018

Sponsor

Barbara Ann Karmanos Cancer Institute

1. Study Identification

Unique Protocol Identification Number

NCT01246206

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

May 2018

Overall Recruitment Status

Completed

Study Start Date

November 2010 (undefined)

Primary Completion Date

October 2013 (Actual)

Study Completion Date

October 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Barbara Ann Karmanos Cancer Institute

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hematological Malignancies

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;

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

21 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Tacrolimus and Thymoglobulin

Arm Type

Experimental

Arm Description

Tacrolimus and Thymoglobulin, as Graft-versus-Host-Disease Prophylaxis

Intervention Type

Drug

Intervention Name(s)

Tacrolimus and Thymoglobulin

Other Intervention Name(s)

PROGRAF®

Intervention Description

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.

Primary Outcome Measure Information:

Title

Incidence of Acute GVHD

Description

Cumulative Incidence of grade II-V acute GVHD with relapse or NRM as competing risks

Time Frame

Assessed first 6 months post transplant

Title

Safety Defined by Serious Adverse Events

Description

Counted the number of participants that experienced any type of grade 3 or higher toxicity.

Time Frame

Assessed first 6 months post transplant

Title

Severity of Acute GVHD

Description

Cumulative Incidence of grade III-V acute GVHD with relapse or NRM as competing risks

Time Frame

Assessed first 6 months post transplant

Secondary Outcome Measure Information:

Title

Determine Incidence of Opportunistic Infections

Time Frame