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

NCT ID: NCT00993486

Last Updated: 2013-06-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-01-31
• Study Completion Date: 2013-04-30

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.

Conditions

Hematologic Diseases; Hematologic Malignancies

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

L1 (dose 1.0x10E4 T-cells/kg)

Group Type: EXPERIMENTAL

Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR)

Intervention Type: BIOLOGICAL

Single intravenous infusion

L2 (dose 5.0x10E4 T-cells/kg)

Group Type: EXPERIMENTAL

Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR)

Intervention Type: BIOLOGICAL

Single intravenous infusion

L3 (dose 1.3x10E5 T-cells/kg)

Group Type: EXPERIMENTAL

Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR)

Intervention Type: BIOLOGICAL

Single intravenous infusion

L4 (dose 3.2x10E5 T-cells/kg)

Group Type: EXPERIMENTAL

Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR)

Intervention Type: BIOLOGICAL

Single intravenous infusion

L5 (dose 7.9x10E5 T-cells/kg)

Group Type: EXPERIMENTAL

Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR)

Intervention Type: BIOLOGICAL

Single intravenous infusion

L6 (dose 2.0x10E6 T-cells/kg)

Group Type: EXPERIMENTAL

Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR)

Intervention Type: BIOLOGICAL

Single intravenous infusion

L7 (dose 5.0x10E6 T-cells/kg)

Group Type: EXPERIMENTAL

Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR)

Intervention Type: BIOLOGICAL

Single intravenous infusion

Interventions

Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR)

Single intravenous infusion

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kiadis Pharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Denis-Claude Roy, MD

Role: PRINCIPAL_INVESTIGATOR

Maisonneuve-Rosemont Hospital, Montréal, Canada

Locations

Maisonneuve-Rosemont Hospital

Montreal, Quebec, Canada

Countries

Canada

References

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.

Reference Type: DERIVED

PMID: 31135970 (View on PubMed)

Other Identifiers

CR-GVH-001

Identifier Type: -

Identifier Source: org_study_id