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
- Conditions
- MedDRA version: 20.0Level: LLTClassification code 10059044Term: Allogeneic peripheral hematopoietic stem cell transplantSystem Organ Class: 100000022080Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]Patients with a hematologic malignancy (AML, ALL, or MDS) who are eligible for a haploidentical HSCTMedDRA version: 20.0Level: LLTClassification code 10000845Term: Acute lymphoblastic leukemiaSystem Organ Class: 100000012958MedDRA version: 20.0Level: PTClassification code 10027703Term: Mismatched donor bone marrow transplantation therapySystem Organ Class: 10042613 - Surgical and medical proceduresMedDRA version: 20.0Level: PTClassification code 10000880Term: Acute myeloid leukaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10028533Term: Myelodysplastic syndromeSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2016-004672-21-ES
- Lead Sponsor
- Kiadis Pharma Netherlands B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 43
1. Any of the following hematologic malignancies:
- Acute myeloid leukemia (AML) in first cytomorphological remission with Disease Risk Index (DRI) intermediate or above, or in second or higher cytomorphological remission
- Acute lymphoblastic leukemia (ALL) in first or higher remission
- Myelodysplastic syndrome (MDS): transfusion-dependent (requiring at least one transfusion per month), or intermediate or higher IPSS-R risk group
2. Clinical justification of allogeneic stem cell transplantation where a suitable HLA matched sibling or unrelated donor is unavailable in a timely manner. An unrelated donor search is not required for a patient to be eligible if the clinical situation dictates an urgent transplantation. Clinical urgency is defined as 6-8 weeks from referral to transplant center or low likelihood of finding a matched unrelated donor
3. Availability of a related haploidentical donor with = 4/8 but < 8/8, or = 5/10 but < 10/10 matches at the HLA-A, -B, -C, -DRB1, and/or -DQB1 loci, as determined by high resolution HLA-typing
4. Karnofsky Performance Status (KPS) = 70%
5. Male or female, age = 18 years and = 70 years
Patients aged = 65 years must have a Sorror score = 3
6. Availability of a donor aged = 16 years and = 75 years who is eligible according to local requirements and regulations
7. For females of childbearing potential who are sexually active and males who have sexual contact with a female of childbearing potential: use of reliable methods of contraception during study participation
8. Given written informed consent (patient and donor)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 185
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10
1. Availability of a suitable fully matched related or unrelated donor in a donor search
2. Prior allogeneic hematopoietic stem cell transplantation
3. Diffusing capacity for carbon monoxide (DLCO) < 50% predicted
4. Left ventricular ejection fraction < 50% (evaluated by echocardiogram or MUGA)
5. AST and/or ALT > 2.5 × ULN (CTCAE grade 2)
6. Bilirubin > 1.5 × ULN (CTCAE grade 2)
7. Creatinine clearance < 50 ml/min (calculated or measured)
8. Positive pregnancy test or breastfeeding of patient or donor (women of childbearing age only)
9. Estimated probability of surviving less than 3 months
10. Known allergy to any of the components of ATIR101 (e.g., dimethyl sulfoxide)
11. Known hypersensitivity to cyclophosphamide or any of its metabolites
12. Known presence of HLA antibodies against the non-shared donor haplotype
13. Positive HIV test
14. Positive CMV test of the patient and negative CMV test of the donor
15. Positive viral test of the donor for HIV-1, HIV-2, HBV, HCV, Treponema pallidum, HTLV 1 (if tested), HTLV-2 (if tested), WNV (if tested), or Zika virus (if tested)
16. Any other condition that, in the opinion of the investigator, makes the patient or donor ineligible for the study
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The 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.;Secondary Objective: Not applicable;Primary end point(s): The primary endpoint of the study is GVHD-free, relapse-free survival (GRFS). GRFS is defined as time from randomization until grade III/IV acute graft-versus-host disease (GVHD), chronic GVHD requiring systemic immunosuppressive treatment, disease relapse, or death, whichever occurs first. This endpoint captures both safety and efficacy.;Timepoint(s) of evaluation of this end point: Throughout the study (no fixed timepoint)
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Overall survival (safety and efficacy), defined as the time from randomization until death from any cause<br>• Progression-free survival (efficacy), defined as the time from randomization until relapse, disease progression, or death, whichever occurs first<br>• Relapse-related mortality (efficacy), defined as the time from randomization to death due to disease relapse or disease progression<br>• Transplant-related mortality (safety and efficacy), defined as the time from randomization to death due to causes other than disease relapse or disease progression;Timepoint(s) of evaluation of this end point: Throughout the study (no fixed timepoint)