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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Zaid Al-Kadhimi, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT01246206
First received: November 21, 2010
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Hematological Malignancies
Drug: Tacrolimus and Thymoglobulin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Tacrolimus and Thymoglobulin, as Graft-versus-Host-Disease Prophylaxis in Patients Undergoing Related Donor Hematopoietic Cell Transplantation

Resource links provided by NLM:


Further study details as provided by Barbara Ann Karmanos Cancer Institute:

Primary Outcome Measures:
  • Incidence and severity of acute GVHD [ Time Frame: Assessed first 6 months post transplant ] [ Designated as safety issue: No ]
  • Safety defined by serious adverse events [ Time Frame: Assessed first 6 months post transplant ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Determine incidence of opportunistic infections [ Time Frame: Followed for up to two years post transplant ] [ Designated as safety issue: No ]
  • Estimate incidence of chronic GVHD at two years [ Time Frame: Followed for up to two years post transplant ] [ Designated as safety issue: No ]
  • Overall and disease free survival at two year, [ Time Frame: Followed for up to two years post transplant ] [ Designated as safety issue: No ]
  • Assess immune response with immuno-correlative studies both pre and at various points post transplant. [ Time Frame: Followed for up to two years post transplant ] [ Designated as safety issue: No ]
  • Determine time to engraftment [ Time Frame: Followed for up to two years post transplant ] [ Designated as safety issue: No ]

Enrollment: 21
Study Start Date: November 2010
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: PROGRAF®

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01246206

Locations
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
Investigators
Principal Investigator: Zaid Al-Kadhimi, M.D. Barbara Ann Karmanos Cancer Institute
  More Information

No publications provided

Responsible Party: Zaid Al-Kadhimi, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT01246206     History of Changes
Obsolete Identifiers: NCT01414127
Other Study ID Numbers: WSU 2009-095
Study First Received: November 21, 2010
Last Updated: May 15, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Barbara Ann Karmanos Cancer Institute:
● 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
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 28, 2014