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Haploidentical Donor vs mMUD in Hematological Malignancies (HAMLET)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03275636
Recruitment Status : Recruiting
First Posted : September 7, 2017
Last Update Posted : August 26, 2021
Information provided by (Responsible Party):
DKMS gemeinnützige GmbH

Brief Summary:
The goal of this trial is to compare the outcome after partially matched (single mismatch) unrelated donor transplantation with haploidentical transplantation in a randomized controlled setting.

Condition or disease Intervention/treatment Phase
AML ALL MDS Biological: Peripheral blood stem cells Phase 2 Phase 3

Detailed Description:

For patients with an indication for allogeneic HCT, the search for a stem cell donor is a challenge. 20% of patients who need an allograft have an HLA-identical sibling available, and for approximately 70% of the remaining patients, a suitable, HLA-well-matched (10/10), unrelated volunteer can be found. For the remaining patients, partially matched (single mismatch) unrelated donors or haploidentical donors are alternative options.

Recently published retrospective single center and registry studies suggest comparable outcomes for HCT from unrelated donors matched at HLA -A, -B, -C, and -DRB1 and haploidentical donors. The number of haploidentical HCT evaluated in these studies was still relatively small and a selection bias for the retrospective comparisons cannot be excluded.

The goal of this trial is to evaluate overall survival of patients with high-risk AML, ALL or MDS after partially matched unrelated or haploidentical donor transplantation..

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 266 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Controlled Trial Comparing Outcome After Hematopoietic Cell Transplantation From a Partially Matched Unrelated Versus Haploidentical Donor
Actual Study Start Date : January 1, 2018
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : October 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Organ Donation

Arm Intervention/treatment
Experimental: Haploidentical donor
Peripheral blood stem cells from Haploidentical donor
Biological: Peripheral blood stem cells
Hematopoietic stem cell transplantation with PBSC
Other Name: PBSC

Active Comparator: partially matched unrelated donor
Peripheral blood stem cells from 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
Biological: Peripheral blood stem cells
Hematopoietic stem cell transplantation with PBSC
Other Name: PBSC

Primary Outcome Measures :
  1. Overall survival [ Time Frame: 2 years ]
    Overall survival calculated from the time of randomization will be the primary endpoint of this trial. Death from any reason will be considered as event.

Secondary Outcome Measures :
  1. Engraftment rate [ Time Frame: day 56 ]

  2. Immune-reconstitution rate [ Time Frame: day56 ]
    Immune-reconstitution rate

  3. Infections [ Time Frame: 2 months after HCT ]
    Severe infections rate

  4. Event Free Survival [ Time Frame: 1 year ]
    Event Free Survival

  5. Graft vs Host Disease [ Time Frame: 1 year ]
    Graft vs Host Disease rate

  6. Graft vs Host Disease-free survival [ Time Frame: 1 year ]
    Graft vs Host Disease-free survival rate

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.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria

  1. 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 by chemotherapy-refractory disease.

    AML with favourable genetic abnormalities (according to ELN guidelines) after relapse or by 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 score)2.

    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.

  2. Fit for transplant according to physician judgement.
  3. No history of cardiac disease and absence of active symptoms, otherwise, documented left ventricular ejection fraction ≥40%.
  4. 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
  5. 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.
  6. 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.

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

  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.

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 identifier (NCT number): NCT03275636

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Contact: Sarah Trost, MSc 0049 351210798 ext 28

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Universitätsklinikum Bonn Recruiting
Bonn, Germany, 53105
Principal Investigator: Tobias Holderried, Dr med         
Universitätsklinikum Dresden Recruiting
Dresden, Germany
Contact: Johannes Schetelig, Prof Dr med         
Universitätsklinikum Frankfurt Recruiting
Frankfurt am Main, Germany, 60595
Principal Investigator: Gesine Bug, Dr med         
Universitätsklinikum Halle (Saale) Recruiting
Halle, Germany, 06120
Principal Investigator: Lutz Peter Müller, PD Dr med         
Universitätsmedizin Mannheim Recruiting
Mannheim, Germany, 68167
Principal Investigator: Stefan Klein, PD Dr med         
Universitätsklinikum Münster Recruiting
Münster, Germany, 48149
Principal Investigator: Matthias Stelljes, PD Dr med         
Klinikum Nürnberg Nord Recruiting
Nürnberg, Germany, 90419
Principal Investigator: Kerstin Schäfer-Eckhard, Dr med         
Robert-Bosch-Krankenhaus Recruiting
Stuttgart, Germany, 70376
Principal Investigator: Martin Kaufmann, Dr med         
Universitätsklinikum Tübingen Recruiting
Tübingen, Germany, 72076
Principal Investigator: Wolfgang Bethge, Prof Dr med         
Sponsors and Collaborators
DKMS gemeinnützige GmbH
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Study Chair: Johannes Schetelig, Prof Dr med Universtitätsklinikum Dresden
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Responsible Party: DKMS gemeinnützige GmbH Identifier: NCT03275636    
Other Study ID Numbers: DKMS-16-01
2015-005399-12 ( EudraCT Number )
First Posted: September 7, 2017    Key Record Dates
Last Update Posted: August 26, 2021
Last Verified: August 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by DKMS gemeinnützige GmbH:
mismatched unrelated donor
hematopoietic stem cell transplantation
donor comparison