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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

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ClinicalTrials.gov Identifier: NCT00993486
Recruitment Status : Completed
First Posted : October 12, 2009
Last Update Posted : June 20, 2013
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
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 or disease Intervention/treatment Phase
Hematologic Diseases Hematologic Malignancies Biological: Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR) Phase 1 Phase 2

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.


Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : January 2005
Primary Completion Date : October 2008
Study Completion Date : April 2013

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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


Outcome Measures

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

Secondary Outcome Measures :
  1. Immune reconstitution [ Time Frame: Until 60 months after ATIR infusion ]
  2. Rate of disease relapse [ Time Frame: Until 60 months after ATIR infusion ]
  3. Occurrence and severity of graft-versus-host disease [ Time Frame: Until 60 months after ATIR infusion ]
  4. Occurrence of adverse drug reactions [ Time Frame: Until 18 months after ATIR infusion ]
  5. Incidence and severity of infections [ Time Frame: Until 18 months after ATIR infusion ]

Eligibility Criteria

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

Responsible Party: Kiadis Pharma
ClinicalTrials.gov Identifier: NCT00993486     History of Changes
Other Study ID Numbers: CR-GVH-001
First Posted: October 12, 2009    Key Record Dates
Last Update Posted: June 20, 2013
Last Verified: June 2013

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