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Fludarabine

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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

Antirheumatic Agents

Cyclophosphamide

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

T-cell depleted HSCT from a related, haploidentical donor, followed by IV infusion with ATIR101 at a single dose of 2×10E6 viable T-cells/kg body weight between 28 and 32 days after the HSCT

T-cell replete HSCT from a related, haploidentical donor, followed by IV infusion of post-transplant cyclophosphamide (PTCy) 50 mg/kg/day at 3 and 4/5 days after the HSCT

ATIR101 is a T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells using photodynamic treatment; single dose of 2×10E6 viable T-cells/kg body weight between 28 and 32 days after the HSCT (intravenous infusion)

High dose post-transplant cyclophosphamide 50 mg/kg/day at 3 and 4/5 days after the HSCT (powder for intravenous infusion)

T-cell depleted graft prepared from peripheral blood stem cells using the CD34+ cell selection method; infused after a total body irradiation (TBI) or non-TBI conditioning regimen

T-cell depleted HSCT from a related, haploidentical donor

T-cell replete (full, non-manipulated) graft prepared from either bone marrow or peripheral blood stem cells; infused after a total body irradiation (TBI) or non-TBI conditioning regimen

T-cell replete HSCT from a related, haploidentical donor

The primary objective of this study is to compare safety and efficacy of a haploidentical T-cell depleted HSCT and adjunctive treatment with ATIR101 versus a haploidentical T cell replete HSCT with post-transplant administration of high dose cyclophosphamide (PTCy) in patients with a hematologic malignancy. An additional objective of the study is to compare the effect of the two treatments on quality of life.

Study CR-AIR-009 is a Phase III randomized controlled multicenter open-label study comparing two parallel groups. After signing informed consent, a total of 250 patients will be randomized in a 1:1 fashion to receive either a T-cell depleted hematopoietic stem cell transplantation (HSCT; CD34 selection) from a related, haploidentical donor, followed by ATIR101 infusion, or a T-cell replete HSCT, followed by a high dose of post-transplant cyclophosphamide (PTCy).

Randomization will use minimization to balance treatment groups with respect to underlying disease (AML, ALL, or MDS), Disease Risk Index (DRI; intermediate risk, high risk, or very high risk) and center. A stochastic treatment allocation procedure will be used so that the treatment assignment is random for all patients entered in the study.

Patients randomized in the ATIR101 group will receive a single ATIR101 dose of 2×10E6 viable T-cells/kg between 28 and 32 days after the HSCT. Patients randomized in the PTCy group will receive cyclophosphamide 50 mg/kg/day at 3 and 4/5 days after the HSCT. All patients will be followed up for at least 24 months post HSCT.

Safety and Efficacy of ATIR101 as Adjunctive Treatment to Blood Stem Cell Transplantation From a Haploidentical Family Donor Compared to Post-transplant Cyclophosphamide in Patients With Blood Cancer

A Phase III, Multicenter, Randomized Controlled Study to Compare Safety and Efficacy of a Haploidentical HSCT and Adjunctive Treatment With ATIR101, a T-lymphocyte Enriched Leukocyte Preparation Depleted ex Vivo of Host Alloreactive T-cells, Versus a Haploidentical HSCT With Post-transplant Cyclophosphamide in Patients With a Hematologic Malignancy

Time to CD3+ \> 0.2×10E9/l in peripheral blood (at two consecutive measurements; time to first measurement)

Quality of life: Foundation for the Accreditation of Cellular Therapy - Bone Marrow Transplantation questionnaire (FACT-BMT)

Quality of life: Short Form 36-item health survey (SF-36)

Quality of life: MD Anderson Symptom Inventory (MDASI)

Defined as the time until acute GVHD grade III/IV, chronic GVHD requiring systemic treatment, relapse, or death, whichever occurs first. Kaplan-Meier estimates (percentage of participants) of GRFS were calculated at 24 months post HSCT.

OS is defined as the time from HSCT until death from any cause. Kaplan-Meier estimates (percentage of participants) of OS were calculated at 24 months post HSCT.

Defined as the time from HSCT until relapse, disease progression, or death, whichever occurs first. Kaplan-Meier estimates (percentage of participants) of PFS were calculated at 24 months post HSCT.

Time from randomization to death due to disease relapse or disease progression

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). Kaplan-Meier estimates (percentage of participants) of PFS were calculated at 24 months post HSCT.

Study was pre-maturely terminated. For the long term safety follow-up (LTFU), up to 24 months post-HSCT, only cumulative SAEs were recorded.

(63 patients had been enrolled (randomized); 32 to ATIR101 group and 31 to PTCy group (intention-to-treat \[ITT\] population). Only patients who received an HSCT and ATIR101 (n=16) or at least one dose of PTCy (n=27) were included in the modified ITT population (MITT). Eight ATIR101, and 22 PTCy treated patients entered 2 year LTFU).

T-cell depleted HSCT from a related, haploidentical donor, followed by IV infusion with ATIR101 at a single dose of 2×10E6 viable T-cells/kg body weight between 28 and 32 days after the HSCT

ATIR101: ATIR101 is a T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells using photodynamic treatment; single dose of 2×10E6 viable T-cells/kg body weight between 28 and 32 days after the HSCT (intravenous infusion)

T-cell depleted HSCT from a related, haploidentical donor: T-cell depleted graft prepared from peripheral blood stem cells using the CD34+ cell selection method; infused after a total body irradiation (TBI) or non-TBI conditioning regimen

T-cell replete HSCT from a related, haploidentical donor, followed by IV infusion of post-transplant cyclophosphamide (PTCy) 50 mg/kg/day at 3 and 4/5 days after the HSCT

Cyclophosphamide: High dose post-transplant cyclophosphamide 50 mg/kg/day at 3 and 4/5 days after the HSCT (powder for intravenous infusion)

T-cell replete HSCT from a related, haploidentical donor: T-cell replete (full, non-manipulated) graft prepared from either bone marrow or peripheral blood stem cells; infused after a total body irradiation (TBI) or non-TBI conditioning regimen

PTCy

Total

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Hematologic malignancy

Klaudia Traudtner, MD. Head of Safety and Pharmacovigilance.

Graft-versus-host Disease-free, Relapse-free Survival (GRFS)

Study was pre-maturely terminated. Data not collected.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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 ATIR101 as Adjunctive Treatment to Blood Stem Cell Transplantation From a Haploidentical Family Donor Compared to Post-transplant Cyclophosphamide in Patients With Blood Cancer	NCT02999854	Acute Myeloid L... Acute Lymphobla... Myelodysplastic...	ATIR101 Cyclophosphamid... T-cell depleted... T-cell replete ...	18 Years - 70 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 atir101

Every month we try and update this database with for atir101 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for atir101

Every month we try and update this database with for atir101 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for atir101 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.