Trial Outcomes & Findings for Safety and Efficacy of Donor T-lymphocytes Depleted ex Vivo of Host Alloreactive T-cells (ATIR) in Patients With a Hematologic Malignancy Who Received a Hematopoietic Stem Cell Transplantation From a Haploidentical Donor (NCT NCT01794299)

NCT ID: NCT01794299

Last Updated: 2021-04-12

Results Overview

TRM is defined as death due to causes other than disease relapse or progression, or other causes which are unrelated to the transplantation procedure (e.g. accident, suicide). The TRM rate is displayed as a function of time using the Kaplan-Meier method. The TRM rate at 6 months post HSCT is estimated from this analysis.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 31 participants
• Primary outcome timeframe: At 6 months post HSCT
• Results posted on: 2021-04-12

Participant Flow

Participant milestones

Measure	ATIR ATIR: Donor T-lymphocytes depleted ex vivo of host alloreactive T-cells using photodynamic treatment. Single intravenous infusion with 2x10E6 viable T-cells/kg.
Overall Study STARTED	31
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	22

Reasons for withdrawal

Measure	ATIR ATIR: Donor T-lymphocytes depleted ex vivo of host alloreactive T-cells using photodynamic treatment. Single intravenous infusion with 2x10E6 viable T-cells/kg.
Overall Study ATIR manufacturing not possible	1
Overall Study Death	14
Overall Study Graft failure	1
Overall Study ATIR batch rejected	2
Overall Study Relapse	2
Overall Study Discontinued from active follow-up	1
Overall Study Relapse and rejection of ATIR batch	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	ATIR n=23 Participants ATIR: Donor T-lymphocytes depleted ex vivo of host alloreactive T-cells using photodynamic treatment. Single intravenous infusion with 2x10E6 viable T-cells/kg.
Age, Continuous	34 years n=23 Participants
Sex: Female, Male Female	13 Participants n=23 Participants
Sex: Female, Male Male	10 Participants n=23 Participants
Human leukocyte antigen (HLA)-match n (%) 3/6	16 Participants n=23 Participants
Human leukocyte antigen (HLA)-match n (%) 4/6	6 Participants n=23 Participants
Human leukocyte antigen (HLA)-match n (%) 5/6	1 Participants n=23 Participants

PRIMARY outcome

Timeframe: At 6 months post HSCT

TRM is defined as death due to causes other than disease relapse or progression, or other causes which are unrelated to the transplantation procedure (e.g. accident, suicide). The TRM rate is displayed as a function of time using the Kaplan-Meier method. The TRM rate at 6 months post HSCT is estimated from this analysis.

Outcome measures

Measure	ATIR n=23 Participants ATIR: Donor T-lymphocytes depleted ex vivo of host alloreactive T-cells using photodynamic treatment. Single intravenous infusion with 2x10E6 viable T-cells/kg.
Transplant-related Mortality (TRM)	13 Kaplan-Meier estimates (%) Interval 5.0 to 36.0

SECONDARY outcome

Timeframe: Up to 24 months post HSCT

Immunophenotyping on peripheral blood samples by means of flow cytometry assessment of immune subsets was done if the absolute lymphocyte count was higher than 0.1×10E9/l

Outcome measures

Measure	ATIR n=23 Participants ATIR: Donor T-lymphocytes depleted ex vivo of host alloreactive T-cells using photodynamic treatment. Single intravenous infusion with 2x10E6 viable T-cells/kg.
Immune Reconstitution Number of participants with CD3 counts above 0.1×10E9/l at 24 months follow up	18 Participants
Immune Reconstitution Number of participants with CD3 counts above 0.2×10E9/l at 24 months follow up	13 Participants

SECONDARY outcome

Timeframe: 6, 12 and 24 months post HSCT

Defined as death due to disease relapse or disease progression. The Kaplan-Meier analysis resulted in estimates and 95% confidence intervals (CI)s.

Outcome measures

Measure	ATIR n=23 Participants ATIR: Donor T-lymphocytes depleted ex vivo of host alloreactive T-cells using photodynamic treatment. Single intravenous infusion with 2x10E6 viable T-cells/kg.
Relapse-related Mortality (RRM) 6 months post HSCT	5 Kaplan-Meier estimates (%) Interval 1.0 to 28.0
Relapse-related Mortality (RRM) 12 months post HSCT	10 Kaplan-Meier estimates (%) Interval 3.0 to 35.0
Relapse-related Mortality (RRM) 24 months post HSCT	25 Kaplan-Meier estimates (%) Interval 10.0 to 55.0

SECONDARY outcome

Timeframe: 6, 12 and 24 months post HSCT

Defined as the time from HSCT until death from any cause. The Kaplan-Meier analysis resulted in estimates and 95% CIs.

Outcome measures

Measure	ATIR n=23 Participants ATIR: Donor T-lymphocytes depleted ex vivo of host alloreactive T-cells using photodynamic treatment. Single intravenous infusion with 2x10E6 viable T-cells/kg.
Overall Survival (OS) 6 months post HSCT	83 Kaplan-Meier estimates (%) Interval 60.0 to 93.0
Overall Survival (OS) 12 months post HSCT	61 Kaplan-Meier estimates (%) Interval 38.0 to 77.0
Overall Survival (OS) 24 months post HSCT	39 Kaplan-Meier estimates (%) Interval 20.0 to 58.0

SECONDARY outcome

Timeframe: 6, 12 and 24 months post HSCT

Defined as the time from HSCT until relapse, disease progression, or death, whichever occurs first. The Kaplan-Meier analysis resulted in estimates and 95% CIs.

Outcome measures

Measure	ATIR n=23 Participants ATIR: Donor T-lymphocytes depleted ex vivo of host alloreactive T-cells using photodynamic treatment. Single intravenous infusion with 2x10E6 viable T-cells/kg.
Progression-free Survival (PFS) 6 months post HSCT	78 Kaplan-Meier estimates (%) Interval 55.0 to 90.0
Progression-free Survival (PFS) 12 months post HSCT	61 Kaplan-Meier estimates (%) Interval 38.0 to 77.0
Progression-free Survival (PFS) 24 months post HSCT	39 Kaplan-Meier estimates (%) Interval 20.0 to 58.0

SECONDARY outcome

Timeframe: Up to 24 months post HSCT

Outcome measures

Measure	ATIR n=23 Participants ATIR: Donor T-lymphocytes depleted ex vivo of host alloreactive T-cells using photodynamic treatment. Single intravenous infusion with 2x10E6 viable T-cells/kg.
Number of Participants With Viral, Fungal, and Bacterial Infections. Any infection, from 1 year to 2 years after HSCT	12 participants
Number of Participants With Viral, Fungal, and Bacterial Infections. Any infection, from HSCT to ATIR infusion	17 participants
Number of Participants With Viral, Fungal, and Bacterial Infections. Any infection, from ATIR infusion to 6 months after HSCT	19 participants
Number of Participants With Viral, Fungal, and Bacterial Infections. Any infection, from 6 months to 1 year after HSCT	13 participants

SECONDARY outcome

Timeframe: Up to 24 months post HSCT

Outcome measures

Measure	ATIR n=23 Participants ATIR: Donor T-lymphocytes depleted ex vivo of host alloreactive T-cells using photodynamic treatment. Single intravenous infusion with 2x10E6 viable T-cells/kg.
Number of Participants With Graft Versus Host Disease (GVHD) Any GVHD, from HSCT to ATIR infusion	2 participants
Number of Participants With Graft Versus Host Disease (GVHD) Any GVHD, from ATIR infusion to 100 days after HSCT.	0 participants
Number of Participants With Graft Versus Host Disease (GVHD) Any GVHD, from 100 days to 6 months after HSCT.	3 participants
Number of Participants With Graft Versus Host Disease (GVHD) Any GVHD, from 6 months to 1 year after HSCT.	3 participants
Number of Participants With Graft Versus Host Disease (GVHD) Any GVHD, from 1 year to 2 years after HSCT.	4 participants

Adverse Events

ATIR

Serious events: 3 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	ATIR n=23 participants at risk ATIR: Donor T-lymphocytes depleted ex vivo of host alloreactive T-cells using photodynamic treatment. Single intravenous infusion with 2x10E6 viable T-cells/kg.
Immune system disorders acute graft versus host disease (aGVHD)	4.3% 1/23
Immune system disorders chronic graft versus host disease (cGVHD)	4.3% 1/23
Blood and lymphatic system disorders Autoimmune haemolytic anaemia	4.3% 1/23

Other adverse events

Measure	ATIR n=23 participants at risk ATIR: Donor T-lymphocytes depleted ex vivo of host alloreactive T-cells using photodynamic treatment. Single intravenous infusion with 2x10E6 viable T-cells/kg.
Immune system disorders aGVHD	17.4% 4/23

Additional Information

Andrew Sandler, MD / Chief Medical Officer

Kiadis Pharma Netherlands B.V.

Phone: +1 206 779 9213

Email: a.sandler@kiadis.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place