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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01246206

Enrollment

Registered

2010-11-23

Start date

2010-11-30

Completion date

2013-10-31

Last updated

2018-06-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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;

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.

Interventions

DRUGTacrolimus 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.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

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

Design outcomes

Primary

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

Secondary

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

Countries

United States

Participant flow

Participants by arm

Arm	Count
Tacrolimus and Thymoglobulin Tacrolimus and Thymoglobulin, as Graft-versus-Host-Disease Prophylaxis 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.	20
Total	20

Arm

Count

Tacrolimus and Thymoglobulin

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

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Patient did not receive study regiments.	1

Baseline characteristics

Characteristic	Tacrolimus and Thymoglobulin
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	3 Participants
Age, Categorical Between 18 and 65 years	17 Participants
Age, Continuous	59.5 years
Region of Enrollment United States	20 participants
Sex: Female, Male Female	14 Participants
Sex: Female, Male Male	6 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	0 / 21
serious Total, serious adverse events	19 / 21

Outcome results

Primary

Incidence of Acute GVHD

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

Time frame: Assessed first 6 months post transplant

Population: All participants

Arm	Measure	Value (NUMBER)
Tacrolimus and Thymoglobulin	Incidence of Acute GVHD	45.0 percentage of participants

Primary

Safety Defined by Serious Adverse Events

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

Time frame: Assessed first 6 months post transplant

Arm	Measure	Value (NUMBER)
Tacrolimus and Thymoglobulin	Safety Defined by Serious Adverse Events	19 participants

Primary

Severity of Acute GVHD

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

Time frame: Assessed first 6 months post transplant

Population: Those participants who contracted Acute GVHD

Arm	Measure	Value (NUMBER)
Tacrolimus and Thymoglobulin	Severity of Acute GVHD	10.0 % of participants with sever aGVHD

Secondary