We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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 (HATCY)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02999854
Recruitment Status : Terminated (Insufficient efficacy, terminated by Sponsor)
First Posted : December 21, 2016
Results First Posted : May 24, 2022
Last Update Posted : May 24, 2022
Sponsor:
Information provided by (Responsible Party):
Kiadis Pharma

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Acute Lymphoblastic Leukemia Myelodysplastic Syndrome Biological: ATIR101 Drug: Cyclophosphamide Procedure: T-cell depleted HSCT from a related, haploidentical donor Procedure: T-cell replete HSCT from a related, haploidentical donor Phase 3

Detailed Description:

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.

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 63 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: 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
Actual Study Start Date : November 29, 2017
Actual Primary Completion Date : November 9, 2021
Actual Study Completion Date : December 17, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: ATIR101
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
 Biological: 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)

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

Procedure: 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


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Graft-versus-host Disease-free, Relapse-free Survival (GRFS) [ Time Frame: 24 months post-HSCT ]
    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.


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: 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.

  2. Progression-free Survival (PFS) [ Time Frame: 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.

  3. Relapse-related Mortality (RRM) [ Time Frame: Through study completion, at least two years post HSCT ]
    Time from randomization to death due to disease relapse or disease progression

  4. Transplant-related Mortality (TRM) [ Time Frame: 24 months post-HSCT ]
    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.


Other Outcome Measures:
  1. Immune Reconstitution [ Time Frame: Through study completion, at least two years post HSCT ]
    Time to CD3+ > 0.2×10E9/l in peripheral blood (at two consecutive measurements; time to first measurement)

  2. Cumulative Incidence of Grade II-IV and Grade III-IV Acute Graft-versus-host-disease (GVHD) [ Time Frame: Through study completion, at least two years post HSCT ]
  3. Cumulative Incidence of Moderate/Severe Chronic GVHD [ Time Frame: Through study completion, at least two years post HSCT ]
  4. Cumulative Incidence of Chronic GVHD Requiring Systemic Immunosuppressive Treatment [ Time Frame: Through study completion, at least two years post HSCT ]
  5. Duration of GVHD Episodes [ Time Frame: Through study completion, at least two years post HSCT ]
  6. Cumulative Incidence of NCI CTCAE Grade 2-5 and Grade 3-5 Infections [ Time Frame: Until 2 years after the HSCT ]
    Viral, fungal, and bacterial infections

  7. Cumulative Incidence of NCI CTCAE Grade 3-5 Adverse Events [ Time Frame: Until 2 years after the HSCT ]
    Viral, fungal, and bacterial infections

  8. FACT-BMT Total Score (Change From Screening) [ Time Frame: Through study completion (Month 3, 6, 12, 24, 36, 48 post HSCT) ]
    Quality of life: Foundation for the Accreditation of Cellular Therapy - Bone Marrow Transplantation questionnaire (FACT-BMT)

  9. SF-36 Total Score (Change From Screening) [ Time Frame: Through study completion (Month 3, 6, 12, 24, 36, 48 post HSCT) ]
    Quality of life: Short Form 36-item health survey (SF-36)

  10. MDASI Total Score (Change From Screening) [ Time Frame: Through study completion (Month 3, 6, 12, 24, 36, 48 post HSCT) ]
    Quality of life: MD Anderson Symptom Inventory (MDASI)

  11. EQ-5D-5L (Change From Screening) [ Time Frame: Through study completion (Month 3, 6, 12, 24, 36, 48 post HSCT) ]
    Quality of life: EQ-5D-5L


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Any of the following hematologic malignancies:

    • Acute myeloid leukemia (AML) in first cytomorphological remission (with < 5% blasts in the bone marrow) with Disease Risk Index (DRI) intermediate or above, or in second or higher cytomorphological remission (with < 5% blasts in the bone marrow)
    • Acute lymphoblastic leukemia (ALL) in first or higher remission (with < 5% blasts in the bone marrow)
    • Myelodysplastic syndrome (MDS): transfusion-dependent (requiring at least one transfusion per month), or intermediate or higher Revised International Prognostic Scoring System (IPSS-R) risk group
  • Clinical justification of allogeneic stem cell transplantation where a suitable HLA matched sibling or unrelated donor is unavailable in a timely manner
  • Availability of a related haploidentical donor with one fully shared haplotype and 2 to 4 mismatches at the HLA-A, -B, -C, and -DRB1 loci of the unshared haplotype, as determined by high resolution human leukocyte antigen (HLA)-typing
  • Karnofsky Performance Status (KPS) ≥ 70%
  • Male or female, age ≥ 18 years and ≤ 70 years. Patients aged ≥ 65 years must have a Sorror score ≤ 3
  • Patient weight ≥ 25 kg and ≤ 130 kg
  • Availability of a donor aged ≥ 16 years and ≤ 75 years who is eligible according to local requirements and regulations. Donors aged < 16 years are allowed if they are the only option for an HSCT, if they are permitted by local regulations, and if the IRB/IEC approves participation in the study.
  • For females of childbearing potential who are sexually active and males who have sexual contact with a female of childbearing potential: willingness to use of reliable methods of contraception (oral contraceptives, intrauterine device, hormone implants, contraceptive injection or abstinence) during study participation
  • Given written informed consent (patient and donor)

Exclusion Criteria:

  • Diagnosis of chronic myelomonocytic leukemia (CMML)
  • Availability of a suitable HLA-matched sibling or unrelated donor in a donor search
  • Prior allogeneic hematopoietic stem cell transplantation
  • Diffusing capacity for carbon monoxide (hemoglobin corrected DLCO) < 50% predicted
  • Left ventricular ejection fraction < 45% (evaluated by echocardiogram or MUGA scan)
  • Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2.5 × upper limit of normal (CTCAE grade 2)
  • Creatinine clearance < 50 ml/min (calculated or measured)
  • Positive pregnancy test or breastfeeding of patient or donor (women of childbearing age only)
  • Estimated probability of surviving less than 3 months
  • Known allergy to any of the components of ATIR101 (e.g., dimethyl sulfoxide)
  • Known hypersensitivity to cyclophosphamide or any of its metabolites
  • Any contraindication for GVHD prophylaxis with mycophenolate mofetil, cyclosporine A, or tacrolimus
  • Known presence of HLA antibodies against the non-shared donor haplotype
  • Positive viral test of the patient or donor for human immunodeficiency virus (HIV)-1, HIV-2, hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum, human T-lymphotropic virus (HTLV)-1 (if tested), HTLV-2 (if tested), West Nile virus (WNV; if tested), or Zika virus (if tested)
  • Any other condition that, in the opinion of the investigator, makes the patient or donor ineligible for the study
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02999854


Locations
Show Show 42 study locations
Sponsors and Collaborators
Kiadis Pharma
Investigators
Layout table for investigator information
Principal Investigator: Denis Claude Roy, Prof MD Research Center and Cellular Therapy Laboratory, Maisonneuve-Rosemont Hospital (Montreal, Canada)
Principal Investigator: Stephan Mielke, Prof MD Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital (Stockholm, Sweden)
  Study Documents (Full-Text)

Documents provided by Kiadis Pharma:
Study Protocol  [PDF] August 23, 2018
Statistical Analysis Plan  [PDF] December 13, 2021

More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Kiadis Pharma
ClinicalTrials.gov Identifier: NCT02999854    
Other Study ID Numbers: CR-AIR-009
2016-004672-21 ( EudraCT Number )
First Posted: December 21, 2016    Key Record Dates
Results First Posted: May 24, 2022
Last Update Posted: May 24, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kiadis Pharma:
Haploidentical stem cell transplantation
Graft-versus-host disease
Immune reconstitution
Alloreactive T-cells
Photodynamic treatment
 Hematologic malignancy
Transplant-related mortality
Overall survival
GRFS
GVHD
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
 Immune System Diseases
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists