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

NCT00993486 | Completed Phase 1

• 1 other identifier: CR-GVH-001
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

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

  Within 30 days after ATIR infusion

Secondary Outcomes (5)

• 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

Study Arms (7)

L1 (dose 1.0x10E4 T-cells/kg)

EXPERIMENTAL

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

L2 (dose 5.0x10E4 T-cells/kg)

EXPERIMENTAL

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

L3 (dose 1.3x10E5 T-cells/kg)

EXPERIMENTAL

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

L4 (dose 3.2x10E5 T-cells/kg)

EXPERIMENTAL

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

L5 (dose 7.9x10E5 T-cells/kg)

EXPERIMENTAL

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

L6 (dose 2.0x10E6 T-cells/kg)

EXPERIMENTAL

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

L7 (dose 5.0x10E6 T-cells/kg)

EXPERIMENTAL

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

Interventions

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

Single intravenous infusion

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)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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);

You may not qualify if:

• 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

Sponsors & Collaborators

• Kiadis Pharma: lead

Study Sites (1)

Maisonneuve-Rosemont Hospital

Montreal, Quebec, H1T 2M4, Canada

Location

Related Publications (1)

• 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.

  PMID: 31135970 DERIVED

MeSH Terms

Conditions

Hematologic Diseases; Hematologic Neoplasms; Graft vs Host Disease

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Neoplasms by Site; Neoplasms; Immune System Diseases

Study Officials

• Denis-Claude Roy, MD

  Maisonneuve-Rosemont Hospital, Montréal, Canada

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2009
• First Posted: October 12, 2009
• Study Start: January 1, 2005
• Primary Completion: October 1, 2008
• Study Completion: April 1, 2013
• Last Updated: June 20, 2013

Record last verified: 2013-06

Locations

CA (1)