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Haploidentical Donor vs mMUD in Hematological Malignancies (HAMLET)

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ClinicalTrials.gov Identifier: NCT03275636
Recruitment Status : Recruiting
First Posted : September 7, 2017
Last Update Posted : August 22, 2018
Sponsor:
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..


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

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

Experimental: partially matched unrelated donor
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 ]
  3. Severe infections rate [ Time Frame: 2 months after HCT ]
  4. Event Free Survival [ Time Frame: 1 year ]
  5. Graft vs Host Disease rate [ Time Frame: 1 year ]
  6. Graft vs Host Disease-free survival rate [ Time Frame: 1 year ]


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

Inclusion Criteria:

  1. Eligible diagnoses are listed below:

    • AML with adverse risk genetic abnormalities (according to the ELN guidelines)
    • AML with intermediate genetic abnormalities (according to ELN guidelines) 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)
    • First CR of high-risk ALL (classification of ALL according to GMALL3), defined by one or more of these:

      • Phenotype (pro B-ALL, early T-ALL, or mature T-ALL).
      • High-risk genetic markers (t(4;11)/ALL1-AF4 or t(9;22)/BCR-ABL).
      • WBC count > 30 GPt/L at diagnosis.
      • Delayed CR (no CR on day 26 after first induction course).
      • Persistence of minimal residual disease after the second induction course.
    • ALL in second complete remission.
  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

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 ClinicalTrials.gov identifier (NCT number): NCT03275636


Contacts
Contact: Raquel Palencia, PharmD 0049 351210798 ext 21 palencia@dkms.de

Locations
Germany
Universitätsklinikum Dresden Recruiting
Dresden, Germany
Contact: Johannes Schetelig, Prof         
Robert Bosch Krankenhaus Recruiting
Stuttgart, Germany
Contact: Martin Kaufmann         
Sponsors and Collaborators
DKMS gemeinnützige GmbH
Investigators
Study Chair: Johannes Schetelig, MD Universtitätsklinikum Dresden

Responsible Party: DKMS gemeinnützige GmbH
ClinicalTrials.gov Identifier: NCT03275636     History of Changes
Other Study ID Numbers: DKMS-16-01
2015-005399-12 ( EudraCT Number )
First Posted: September 7, 2017    Key Record Dates
Last Update Posted: August 22, 2018
Last Verified: August 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by DKMS gemeinnützige GmbH:
Haploidentical
mismatched unrelated donor
hematopoietic stem cell transplantation
donor comparison