Dose-ranging Study of a Single Administration of T-cell Add-back Depleted of Host Alloreactive Cells in Patients Undergoing a Peripheral Blood Stem Cell Transplant From a Related, Haploidentical Donor

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Kiadis Pharma
ClinicalTrials.gov Identifier:
NCT00993486
First received: October 9, 2009
Last updated: June 19, 2013
Last verified: June 2013
  Purpose

The purpose of this study is to determine the maximum tolerated dose and evaluate the safety of the administration of donor lymphocytes depleted of alloreactive T-cells following a stem cell transplant from a related, haploidentical donor, in patients with severe hematologic malignancies.


Condition Intervention Phase
Hematologic Diseases
Hematologic Malignancies
Biological: Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Phase I, Dose-ranging, Open-label, Study of a Single Administration of T-cells Add-back Depleted of Host Alloreactive Cells Using Theralux™ Therapy, Following Haploidentical Peripheral Blood Stem Cell Transplantation Submitted to CD34+ Cell Selection, in Patients With Severe Hematologic Malignancies

Resource links provided by NLM:


Further study details as provided by Kiadis Pharma:

Primary Outcome Measures:
  • Dose limiting toxicity, defined as acute graft-versus-host disease grade III or IV [ Time Frame: Within 30 days after ATIR infusion ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Immune reconstitution [ Time Frame: Until 60 months after ATIR infusion ] [ Designated as safety issue: No ]
  • Rate of disease relapse [ Time Frame: Until 60 months after ATIR infusion ] [ Designated as safety issue: No ]
  • Occurrence and severity of graft-versus-host disease [ Time Frame: Until 60 months after ATIR infusion ] [ Designated as safety issue: Yes ]
  • Occurrence of adverse drug reactions [ Time Frame: Until 18 months after ATIR infusion ] [ Designated as safety issue: Yes ]
  • Incidence and severity of infections [ Time Frame: Until 18 months after ATIR infusion ] [ Designated as safety issue: Yes ]

Enrollment: 19
Study Start Date: January 2005
Study Completion Date: April 2013
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: L1 (dose 1.0x10E4 T-cells/kg) Biological: Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR)
Single intravenous infusion
Experimental: L2 (dose 5.0x10E4 T-cells/kg) Biological: Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR)
Single intravenous infusion
Experimental: L3 (dose 1.3x10E5 T-cells/kg) Biological: Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR)
Single intravenous infusion
Experimental: L4 (dose 3.2x10E5 T-cells/kg) Biological: Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR)
Single intravenous infusion
Experimental: L5 (dose 7.9x10E5 T-cells/kg) Biological: Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR)
Single intravenous infusion
Experimental: L6 (dose 2.0x10E6 T-cells/kg) Biological: Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR)
Single intravenous infusion
Experimental: L7 (dose 5.0x10E6 T-cells/kg) Biological: Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR)
Single intravenous infusion

Detailed Description:

Allogeneic stem cell transplantation is the treatment of choice for many patients with leukemia and other hematologic malignancies. However, a major limitation of this therapy is that for a significant number of patients no fully HLA-matched donor can be found. The application of partially HLA-matched (haploidentical) family donors, who are virtually always available, has some complications. If there is no T-cell add-back it increases the risk for life-threatening infections and disease relapse, while in case of T-cell add-back the risk of graft-versus-host disease is raised.

Kiadis Pharma has developed a method to selectively deplete host alloreactive T-cells through photodynamic therapy, using TH9402 ex vivo. The donor lymphocyte preparation depleted of functional alloreactive T-cells (ATIR) are administered to the patient 4-6 weeks after the stem cell transplant. This method enables early immune reconstitution while preventing graft-versus-host disease.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Any of the following hematologic malignancies: very high risk leukemia, acute leukemia, chronic myeloid leukemia (CML), lymphoma, multiple myeloma (MM), myelodysplastic syndrome (MDS)
  • Incompatibility at two to three loci (HLA-A, B and/or DR) or a single DR locus of the unshared haplotype between the donor and recipient
  • Life expectancy of at least 3 months
  • Satisfactory performance status (ECOG ≤ 2);

Exclusion Criteria:

  • Possibility of performing an allogeneic transplant with an HLA (human leukocyte antigen) matched sibling donor
  • Availability of an 6/6 HLA-A, B and DRB1 matched unrelated donor within 2-3 months;
  • Pregnancy
  • Viral hepatitis (B or C)
  • Active serious infectious process
  • HIV positivity;
  • Systemic dysfunction (cardiac, pulmonary, hepatic and renal) contra-indicating allogeneic stem cell transplantation
  • Prior allogeneic transplantation
  • Prior autologous transplantation within twelve months of baseline visit
  • Any abnormal condition or laboratory result that is considered by the principal investigator capable of altering patient condition or study outcome
  • Active central nervous system (CNS) disease at baseline
  • Participation in a trial with an investigational agent within 30 days prior to entry in the study
  • Malignant cells in circulating peripheral blood (> 25%)
  • Other active malignant disease that would severely limit life expectancy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00993486

Locations
Canada, Quebec
Maisonneuve-Rosemont Hospital
Montreal, Quebec, Canada, H1T 2M4
Sponsors and Collaborators
Kiadis Pharma
Investigators
Principal Investigator: Denis-Claude Roy, MD Maisonneuve-Rosemont Hospital, Montréal, Canada
  More Information

No publications provided

Responsible Party: Kiadis Pharma
ClinicalTrials.gov Identifier: NCT00993486     History of Changes
Other Study ID Numbers: CR-GVH-001
Study First Received: October 9, 2009
Last Updated: June 19, 2013
Health Authority: Canada: Health Canada

Keywords provided by Kiadis Pharma:
Haploidentical stem cell transplantation
Graft-versus-host disease
Immune reconstitution
Alloreactive T-cells
Photodepletion
TH9402
Transplant related mortality
Hematologic malignancy

Additional relevant MeSH terms:
Neoplasms
Hematologic Diseases
Hematologic Neoplasms
Neoplasms by Site

ClinicalTrials.gov processed this record on April 16, 2014