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

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

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.

Study Overview

• Status: Completed
• Conditions: Hematologic Diseases; Hematologic Malignancies
• Intervention / Treatment: Biological: Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR)

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 Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Maisonneuve-Rosemont Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dose limiting toxicity, defined as acute graft-versus-host disease grade III or IV	Within 30 days after ATIR infusion

Secondary Outcome Measures

Outcome Measure	Time Frame
Immune reconstitution	Until 60 months after ATIR infusion
Rate of disease relapse	Until 60 months after ATIR infusion
Occurrence and severity of graft-versus-host disease	Until 60 months after ATIR infusion
Occurrence of adverse drug reactions	Until 18 months after ATIR infusion
Incidence and severity of infections	Until 18 months after ATIR infusion

Collaborators and Investigators

• Sponsor: Kiadis Pharma
• Investigators: Principal Investigator: Denis-Claude Roy, MD, Maisonneuve-Rosemont Hospital, Montréal, Canada

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: October 9, 2009
• First Submitted That Met QC Criteria: October 9, 2009
• First Posted (Estimate): October 12, 2009

Study Record Updates

• Last Update Posted (Estimate): June 20, 2013
• Last Update Submitted That Met QC Criteria: June 19, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Transplant related mortality; Graft-versus-host disease; Hematologic malignancy; Immune reconstitution; Haploidentical stem cell transplantation; Alloreactive T-cells; Photodepletion; TH9402
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Neoplasms; Hematologic Diseases
• Other Study ID Numbers: CR-GVH-001