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Antilymphocyte Serum

T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons).

ATIR101

CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended:

* Total Body Irradiation (TBI) regime
* Non-TBI regime

(See below for details)

Haploidentical hematopoietic stem cell transplantation (HSCT)

* Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions)
* Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.

TBI regime

* Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1
* ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.

Non-TBI regime

Denis Claude Roy, Prof MD

Stephan Mielke, Prof MD

The purpose of this study is to determine whether a repeat dose administration of ATIR101 is safe and effective when infused in patients with a hematologic malignancy following a T-cell depleted stem cell graft from a related haploidentical donor. All patients are planned to receive two ATIR101 doses of 2×10E6 viable T-cells/kg, unless the second dose is reduced or halted for safety reasons.

Study CR-AIR-008 is an exploratory, open-label, multicenter study. After signing informed consent, patients will receive a hematopoietic stem cell transplantation (HSCT) from a related, haploidentical donor, followed by a first ATIR101 infusion at a dose of 2×10E6 viable T-cells/kg between 28 and 32 days after the HSCT. Patients will receive a second ATIR101 infusion at a dose of 2×10E6 viable T-cells/kg between 70 and 74 days after the HSCT. To evaluate safety of the second dose administration, the first 6 patients treated will be evaluated for the occurrence of dose limiting toxicity (DLT), defined as acute GvHD grade III/IV within 120 days post HSCT (or within 42 days after the second ATIR101 infusion in case of prior dose delays). If within the first 6 patients no DLT is observed, treatment of the remaining 9 patients will continue with two ATIR101 doses of 2×10E6 viable T cells/kg. If within the first 6 patients at least 2 patients show DLT, the second ATIR101 infusion will be adjusted to a dose of 1×10E6 viable T cells/kg. If in one of the next 3 patients treated at this lower dose again DLT is observed, the second ATIR101 infusion will be halted and the remaining patients will be given only a single dose of ATIR101.

All patients treated with ATIR101 will be followed up until 12 months after the HSCT. Assessments will be performed at weekly visits from the day of the first ATIR101 infusion (Week 4) until 6 weeks after the second ATIR101 infusion (Week 16), at monthly visits from 4 until 6 months after the HSCT, and every 3 months from 6 until 12 months after the HSCT.

Safety and Efficacy of Two Doses of ATIR101, a T-lymphocyte Enriched Leukocyte Preparation Depleted of Host Alloreactive T-cells, in Patients With a Hematologic Malignancy Who Received a Hematopoietic Stem Cell Transplantation From a Haploidentical Donor

An Exploratory, Open-label, Multicenter Study to Evaluate the Safety and Efficacy of a Two-dose Regimen of ATIR101, a T-lymphocyte Enriched Leukocyte Preparation Depleted ex Vivo of Host Alloreactive T-cells (Using Photodynamic Treatment), in Patients With a Hematologic Malignancy, Who Received a CD34-selected Hematopoietic Stem Cell Transplantation From a Haploidentical Donor

Defined as CD3+ in peripheral blood higher than 0.2×10E9/L at 6 and 12 months post HSCT.

Infection was defined as (1) a clinically apparent infectious disease with symptoms or (2) a viral reactivation. Severity was graded according to CTCAE vs. 4.0

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)

Defined as death due to disease relapse or disease progression

Defined as the time from HSCT until death from any cause

Defined as the time from HSCT until relapse, disease progression, or death, whichever occurs first

Defined as the time until acute GVHD grade III/IV, chronic GVHD requiring systemic treatment, relapse, or death, whichever occurs first

Kiadis Pharma

ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons).

Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended:

* Total Body Irradiation (TBI) regime
* Non-TBI regime

(See below for details)

TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions)

* Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.

Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4

* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1
* ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

Canada

Belgium

United Kingdom

Germany

Region of Enrollment

Andrew Sandler, MD / Chief Medical Officer

Single dose of ATIR101, grade III/IV acute GVHD within 180 days after HSCT

Two doses of ATIR101, Grade III/IV acute GVHD within 180 days after HSCT

The primary study endpoint, grade III/IV acute GVHD within 180 days after HSCT, was met for two patients treated with two doses of ATIR101.

Two patients developed grade III/IV acute GVHD within 180 days after HSCT treated with a single dose of ATIR101.

Incidence of Acute Graft Versus Host Disease (GVHD) Grade III/IV

Single dose group acute GVHD between 6 and 12 months after HSCT

Double dose group acute GVHD between 6 and 12 months after HSCT

Single dose group chronic GVHD between 6 and 12 months after HSCT

Double dose group chronic GVHD between 6 and 12 months after HSCT

7 patients in the single dose and 4 patients in the double dose were analysed to make a total of 11 patients analysed.

Incidence and Severity of Acute and Chronic GVHD

Cumulative incidence estimates of T-cell reconstitution, 6 months post HSCT. Single dose group.

Cumulative incidence estimates of T-cell reconstitution, 6 months post HSCT. Double dose group.

Cumulative incidence estimates of T-cell reconstitution, 12 months post HSCT. Single dose group.

Cumulative incidence estimates of T-cell reconstitution, 12 months post HSCT. Double dose group.

Cumulative incidence estimates of T-cell reconstitution at 6 and 12 months post HSCT were analyzed for the single dose group (N=9) and double dose group (N=6).

Percentage of Participants Who Achieved T-Cell Reconstitution at 6 and 12 Months Post HSCT

Any infection

Severity, grade 1-2

Severity, grade 3-5

Viral, Fungal, and Bacterial Infections

Single-dose group, cumulative estimates of TRM

Double-dose group, cumulative estimates of TRM

Nine participants received a single dose of ATIR101 and 6 participants received a double dose of ATIR101

Transplant-related Mortality (TRM)

Single dose group, cumulative estimates of RRM 12 months post HSCT

Double dose group, cumulative estimates of RRM 12 months post HSCT

Relapse-related Mortality (RRM)

Single dose group, Kaplan-Meier estimates of OS 12 months post HSCT

Double dose group, Kaplan-Meier estimates of OS 12 months post HSCT

Overall Survival (OS)

Single dose group, Kaplan-Meier estimates of PFS 12 months post HSCT

Double dose group, Kaplan-Meier estimates of PFS 12 months post HSCT

Progression-free Survival (PFS)

Single dose, Kaplan-Meier estimates of GRFS

Double dose, Kaplan-Meier estimates of GRFS

Nine subjects received a single dose of ATIR101 and 6 subjects received a double dose of ATIR101.

GVHD-free, Relapse-free Survival (GRFS)

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Safety and Efficacy of Two Doses of ATIR101, a T-lymphocyte Enriched Leukocyte Preparation Depleted of Host Alloreactive T-cells, in Patients With a Hematologic Malignancy Who Received a Hematopoietic Stem Cell Transplantation From a Haploidentical Donor	NCT02500550	Acute Myeloid L... Acute Lymphobla... Myelodysplastic...	ATIR101 Haploidentical ... TBI regime Non-TBI regime	18 Years - 65 Years	Kiadis Pharma
Safety and Efficacy of Two Doses of ATIR101, a T-lymphocyte Enriched Leukocyte Preparation Depleted of Host Alloreactive T-cells, in Patients With a Hematologic Malignancy Who Received a Hematopoietic Stem Cell Transplantation From a Haploidentical Donor	NCT02500550	Acute Myeloid L... Acute Lymphobla... Myelodysplastic...	ATIR101 Haploidentical ... TBI regime Non-TBI regime	18 Years - 65 Years	Kiadis Pharma

Spots Global Cancer Trial Database for haploidentical hematopoietic stem cell transplantation (hsct)