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
This study is ongoing, but not recruiting participants.
Sponsor:
Kiadis Pharma
Information provided by (Responsible Party):
Kiadis Pharma
ClinicalTrials.gov Identifier:
NCT00993486
First received: October 9, 2009
Last updated: February 11, 2013
Last verified: February 2013
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Purpose
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 | Intervention | Phase |
|---|---|---|
|
Hematologic Diseases Hematologic Malignancies |
Biological: Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR) |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: 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 |
Resource links provided by NLM:
Further study details as provided by Kiadis Pharma:
Primary Outcome Measures:
- Dose limiting toxicity, defined as acute graft-versus-host disease grade III or IV [ Time Frame: Within 30 days after ATIR infusion ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Immune reconstitution [ Time Frame: Until 60 months after ATIR infusion ] [ Designated as safety issue: No ]
- Rate of disease relapse [ Time Frame: Until 60 months after ATIR infusion ] [ Designated as safety issue: No ]
- Occurrence and severity of graft-versus-host disease [ Time Frame: Until 60 months after ATIR infusion ] [ Designated as safety issue: Yes ]
- Occurrence of adverse drug reactions [ Time Frame: Until 18 months after ATIR infusion ] [ Designated as safety issue: Yes ]
- Incidence and severity of infections [ Time Frame: Until 18 months after ATIR infusion ] [ Designated as safety issue: Yes ]
| Enrollment: | 19 |
| Study Start Date: | January 2005 |
| Estimated Study Completion Date: | June 2013 |
| Primary Completion Date: | October 2008 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| 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
|
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.
Eligibility| Ages Eligible for Study: | 18 Years to 50 Years |
| Genders Eligible for Study: | Both |
| 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
Please refer to this study by its ClinicalTrials.gov identifier: 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
No publications provided
| Responsible Party: | Kiadis Pharma |
| ClinicalTrials.gov Identifier: | NCT00993486 History of Changes |
| Other Study ID Numbers: | CR-GVH-001 |
| Study First Received: | October 9, 2009 |
| Last Updated: | February 11, 2013 |
| Health Authority: | Canada: Health Canada |
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 Hematologic Neoplasms Neoplasms by Site |
ClinicalTrials.gov processed this record on May 16, 2013