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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by:
Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT01246206
First received: November 21, 2010
Last updated: August 6, 2012
Last verified: August 2012
  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: Allocation: Non-Randomized
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 ]

Estimated Enrollment: 22
Study Start Date: November 2010
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (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:

  1. Suitable related donor as determined by the treating physician.
  2. High resolution molecular HLA typing mandatory for HLA Class I and II.
  3. 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. These hematologic malignancies include: Non-Hodgkins lymphoma, Hodgkin's disease, AML or ALL, MDS, CML, Multiple Myeloma, CLL, Myelofibrosis and other myeloproliferative disorders.
  4. Age >=18 and able to cooperate with oral medication intake (age>18 for section 7, immuno-correlative studies due to the volume of the blood draws)
  5. Peripheral blood stem cells
  6. Agrees to participate, and informed consent signed
  7. KPS>60, ECOG performance status <=2
  8. Creatinine <2.0 mg/dl or creatinine clearance >50 ml/min
  9. Ejection fraction >45%
  10. Serum bilirubin, Liver enzymes less than 3 X upper limit of normal
  11. Lung function tests >45% predicted

Exclusion Criteria:

  1. Age <18 years and >70 years
  2. Bone marrow or Ex vivo engineered or processed graft (CD34+ enrichment, T-cell depletion, etc).
  3. Patients with documented uncontrolled Central Nervous System disease
  4. Active donor or recipient serology positive for human immunodeficiency virus (HIV)
  5. Known contraindication to administration of tacrolimus or Thymoglobulin
  6. Active Hepatitis B or C
  7. Women who are pregnant or nursing..
  Contacts and Locations
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, M.D., Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT01246206     History of Changes
Other Study ID Numbers: WSU 2009-095
Study First Received: November 21, 2010
Last Updated: August 6, 2012
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 April 16, 2014