A randomized controlled trial comparing outcome after hematopoietic cell transplantation from a partially matched unrelated versus haploidentical donor

Phase 1

• Conditions: Patients with high-risk AML, ALL or MDS which have to undergo allogenic transplantaion.; MedDRA version: 21.0Level: LLTClassification code 10024349Term: Leukemia myeloidSystem Organ Class: 100000004864; MedDRA version: 20.0Level: LLTClassification code 10024337Term: Leukemia lymphaticSystem Organ Class: 100000004864; MedDRA version: 20.0Level: LLTClassification code 10068361Term: MDSSystem Organ Class: 100000004864; MedDRA version: 20.1Level: LLTClassification code 10024330Term: Leukemia acuteSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-005399-12-DE
• Lead Sponsor: DKMS gemeinnützige GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-12-01
• Last Update Posted: 15 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 266

Inclusion Criteria

1) Signed written informed consent.
2) Males and females aged =18 years old.
3) Eligible diagnoses are listed below:
• AML with adverse risk genetic abnormalities (according to the ELN guidelines)1.
• AML with intermediate genetic abnormalities (according to ELN guidelines) either in first complete remission, after relapse, or with chemotherapy-refractory disease.
• AML with favourable genetic abnormalities (according to ELN guidelines) after relapse or with chemotherapy-refractory disease, except APL.
• AML with undefined genetic risk classification after relapse or with chemotherapy-refractory disease.
• AML arising from myelodysplastic syndrome (MDS) or a myeloproliferative neoplasia, except if favourable genetic abnormalities (according to ELN guidelines) are present.
• Therapy-related myeloid neoplasia except if favorable genetic abnormalities (according to ELN guidelines) are present.
• MDS with high risk or very high risk disease (according to the IPSS-R score2).
• First CR of high-risk ALL, defined by one or more of these:
- Early or mature T-ALL (CD1a negative).
- Pro B-ALL with t(4v;11); KMT2A-rearrangements
- Presence of BCR-ABL and/or t(9;22).
- Persistence of minimal residual disease after the second induction course.
• ALL with or without complete remission after salvage therapy following poor response to induction therapy
• ALL after haematological or molecular relapse.
4) Fit for transplant according to physician judgement.
5) No history of cardiac disease and absence of active symptoms, otherwise, documented left ventricular ejection fraction =40%.
6) No history of chronic pulmonary disease and absence of dyspnea. Otherwise, documented diffusion lung capacity for carbon monoxide (DLCO) =40% or FEV1/FVC = 50% despite appropriate treatment
7) Availability of =1 unrelated donor with a single allele or antigen mismatch at HLA-A, -B, -C, or -DRB1 and no concurrent DQB1 mismatch (9/10) shown by confirmatory typing.
8) Availability of at least one haploidentical donor meeting the following criteria:
• Donor is a biologic parent / child of the patient or haploidentity has been confirmed for patient’s relatives by HLA-Typing.
• The donor has expressed his / her will to donate, and has no contraindications against a stem cell donation by medical history.
• Donor age is =18 years and =75 years.
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 266
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 266

Exclusion Criteria

1)Relapse or graft failure after a first allogeneic transplantation.
2)Thymic ALL in first complete remission.
3)Severe organ dysfunction defined by either of the following three criteria:
•Patients who receive supplementary continuous oxygen.
•Serum bilirubin >1.5 x ULN (if not considered Gilbert-Syndrome) or ASAT/ALAT >5 x ULN.
•Estimated Glomerular Filtration Rate (GFR) < 40 ml/min, where:
Estimated GFR (mL/min/1.73 m2) = 186 x (Serum Creatinine)-1.154 x (age in years)-0.203 x (0.742 if patient is female) x (1.212 if patient is black)
4)Uncontrolled infection at the time of enrollment.
5)Pregnant or breast-feeding women.
6)An HLA-identical sibling donor or 8/8 (HLA-A, -B, -C, or -DRB1) matched unrelated donor is available and suitable to donate prior to
randomization.
7)Men unable or unwilling to use adequate contraception methods from enrollment to minimum of six months after the last dose of
chemotherapy.
8)Women of childbearing potential except those who fulfill the following criteria: Post-menopausal or post-operative or continuous and
correct application of a contraception method with a Pearl Index <1% or sexual abstinence or vasectomy of the sexual partner.
9)Simultaneous participation in another clinical trial.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate overall mortality of patients with high-risk AML, ALL or MDS after partially matched unrelated or haploidentical donor transplantation.;Secondary Objective: Event-free survival, time to transplantation, relapse incidence, the incidences of acute and chronic GvHD, severe infections and rate of graft failure.;Primary end point(s): Overall survival ;Timepoint(s) of evaluation of this end point: max. five years after randomisation

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Event-free survival, time to transplantation, relapse incidence, the incidences of acute and chronic GvHD, severe infections and rate of graft failure.;Timepoint(s) of evaluation of this end point: day 56 after transplant and max. 5 years after randomisation