Clinical trial NCT01246206: 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
Overall status: COMPLETED
Phase: PHASE2
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;
Lead sponsor: Barbara Ann Karmanos Cancer Institute
Sponsor class: OTHER
First posted: 2010-11-23
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Incidence of Acute GVHD
timeFrame: Assessed first 6 months post transplant
measure: Safety Defined by Serious Adverse Events
timeFrame: Assessed first 6 months post transplant
measure: Severity of Acute GVHD
timeFrame: Assessed first 6 months post transplant
Secondary outcomes:
measure: Determine Incidence of Opportunistic Infections
timeFrame: Followed for up to two years post transplant
measure: Estimate Incidence of Chronic GVHD at Two Years
timeFrame: Followed for up to two years post transplant
measure: Overall Survival at Two Year,
timeFrame: Followed for up to two years post transplant
measure: Determine Time to Engraftment ("G500")
timeFrame: Followed for up to two years post transplant
measure: Determine Time to Engraftment ("PLT20")
timeFrame: Followed for up to two years post transplant
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
Study officials:
affiliation: Barbara Ann Karmanos Cancer Institute
name: Zaid Al-Kadhimi, M.D.
role: PRINCIPAL_INVESTIGATOR
References: