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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

Primary Purpose

Hematologic Diseases, Hematologic Malignancies

Status
Completed
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR)
Sponsored by
Kiadis Pharma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hematologic Diseases focused on measuring Haploidentical stem cell transplantation, Graft-versus-host disease, Immune reconstitution, Alloreactive T-cells, Photodepletion, TH9402, Transplant related mortality, Hematologic malignancy

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Maisonneuve-Rosemont Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

L1 (dose 1.0x10E4 T-cells/kg)

L2 (dose 5.0x10E4 T-cells/kg)

L3 (dose 1.3x10E5 T-cells/kg)

L4 (dose 3.2x10E5 T-cells/kg)

L5 (dose 7.9x10E5 T-cells/kg)

L6 (dose 2.0x10E6 T-cells/kg)

L7 (dose 5.0x10E6 T-cells/kg)

Arm Description

Outcomes

Primary Outcome Measures

Dose limiting toxicity, defined as acute graft-versus-host disease grade III or IV

Secondary Outcome Measures

Immune reconstitution
Rate of disease relapse
Occurrence and severity of graft-versus-host disease
Occurrence of adverse drug reactions
Incidence and severity of infections

Full Information

First Posted
October 9, 2009
Last Updated
June 19, 2013
Sponsor
Kiadis Pharma
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1. Study Identification

Unique Protocol Identification Number
NCT00993486
Brief Title
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
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 Type
Interventional

2. Study Status

Record Verification Date
June 2013
Overall Recruitment Status
Completed
Study Start Date
January 2005 (undefined)
Primary Completion Date
October 2008 (Actual)
Study Completion Date
April 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kiadis Pharma

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematologic Diseases, Hematologic Malignancies
Keywords
Haploidentical stem cell transplantation, Graft-versus-host disease, Immune reconstitution, Alloreactive T-cells, Photodepletion, TH9402, Transplant related mortality, Hematologic malignancy

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
L1 (dose 1.0x10E4 T-cells/kg)
Arm Type
Experimental
Arm Title
L2 (dose 5.0x10E4 T-cells/kg)
Arm Type
Experimental
Arm Title
L3 (dose 1.3x10E5 T-cells/kg)
Arm Type
Experimental
Arm Title
L4 (dose 3.2x10E5 T-cells/kg)
Arm Type
Experimental
Arm Title
L5 (dose 7.9x10E5 T-cells/kg)
Arm Type
Experimental
Arm Title
L6 (dose 2.0x10E6 T-cells/kg)
Arm Type
Experimental
Arm Title
L7 (dose 5.0x10E6 T-cells/kg)
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR)
Intervention Description
Single intravenous infusion
Primary Outcome Measure Information:
Title
Dose limiting toxicity, defined as acute graft-versus-host disease grade III or IV
Time Frame
Within 30 days after ATIR infusion
Secondary Outcome Measure Information:
Title
Immune reconstitution
Time Frame
Until 60 months after ATIR infusion
Title
Rate of disease relapse
Time Frame
Until 60 months after ATIR infusion
Title
Occurrence and severity of graft-versus-host disease
Time Frame
Until 60 months after ATIR infusion
Title
Occurrence of adverse drug reactions
Time Frame
Until 18 months after ATIR infusion
Title
Incidence and severity of infections
Time Frame
Until 18 months after ATIR infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Denis-Claude Roy, MD
Organizational Affiliation
Maisonneuve-Rosemont Hospital, Montréal, Canada
Official's Role
Principal Investigator
Facility Information:
Facility Name
Maisonneuve-Rosemont Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
31135970
Citation
Roy DC, Lachance S, Cohen S, Delisle JS, Kiss T, Sauvageau G, Busque L, Ahmad I, Bernard L, Bambace N, Boumedine RS, Guertin MC, Rezvani K, Mielke S, Perreault C, Roy J. Allodepleted T-cell immunotherapy after haploidentical haematopoietic stem cell transplantation without severe acute graft-versus-host disease (GVHD) in the absence of GVHD prophylaxis. Br J Haematol. 2019 Sep;186(5):754-766. doi: 10.1111/bjh.15970. Epub 2019 May 28.
Results Reference
derived

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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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