AMLPhase 2/3HAMLETNCT03275636
Haploidentical Donor vs mMUD in Hematological Malignancies
A Phase 2/3 study testing Peripheral blood stem cells in people with AML and ALL, run by DKMS gemeinnützige GmbH at 9 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- Peripheral blood stem cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 98 participants
- Where
- 9 sitesGermany
- Study dates
- 1 Jan 2018to 13 Apr 2024
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- Fit for transplant according to physician judgement.
- No history of cardiac disease and absence of active symptoms, otherwise, documented left ventricular ejection fraction ≥40%.
- 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
- 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.
- 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.
Who cannot join
- Relapse or graft failure after a first allogeneic transplantation.
- Thymic ALL in first complete remission.
- 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
- Uncontrolled infection at the time of enrollment.
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- Pregnant or breast-feeding women.
- 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.
- Men unable or unwilling to use adequate contraception methods from enrollment to minimum of six months after the last dose of chemotherapy.
- 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.
- Simultaneous participation in another clinical trial.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Germany9 sites
Universitätsklinikum Bonn
Bonn, 53105
Universitätsklinikum Dresden
Dresden
Universitätsklinikum Frankfurt
Frankfurt am Main, 60595
Universitätsklinikum Halle (Saale)
Halle, 06120
Universitätsmedizin Mannheim
Mannheim, 68167
Universitätsklinikum Münster
Münster, 48149
Klinikum Nürnberg Nord
Nuremberg, 90419
Robert-Bosch-Krankenhaus
Stuttgart, 70376
Universitätsklinikum Tübingen
Tübingen, 72076
About this study
Official title: A Randomized Controlled Trial Comparing Outcome After Hematopoietic Cell Transplantation From a Partially Matched Unrelated Versus Haploidentical Donor
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.
Read the 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..
- Being tested
- Peripheral blood stem cells
- Keywords
- Haploidentical, mismatched unrelated donor, hematopoietic stem cell transplantation, donor comparison
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Peripheral blood stem cellsBiological
Also called PBSC
Hematopoietic stem cell transplantation with PBSC
| Study group | Role | What they receive |
|---|---|---|
| Haploidentical donor | Experimental | Peripheral blood stem cells from Haploidentical donor Receives: Biological: Peripheral blood stem cells |
| partially matched unrelated donor | Active comparator | 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 Receives: Biological: Peripheral blood stem cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
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.
Measured: 2 years
Secondary outcomes (6)
Engraftment rate
Engraftment
Measured: day 56
Immune-reconstitution rate
Immune-reconstitution rate
Measured: day56
Infections
Severe infections rate
Measured: 2 months after HCT
Event Free Survival
Event Free Survival
Measured: 1 year
Graft vs Host Disease
Graft vs Host Disease rate
Measured: 1 year
Graft vs Host Disease-free survival
Graft vs Host Disease-free survival rate
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2017
- Study start1 Jan 2018
- Primary completion13 Apr 2024
- Study completion13 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AMLStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 98 participants (actual)
Sponsor and investigators
- Lead sponsor
- DKMS gemeinnützige GmbH
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Johannes Schetelig, Prof Dr med, Study chair, Universtitätsklinikum Dresden
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03275636
- Sponsor's protocol ID
- DKMS-16-01
- Other IDs
- 2015-005399-12, 2015
- Acronym
- HAMLET
- Status last verified
- Aug 2024
- First submitted
- 4 Sep 2017
- Last updated
- 7 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial Comparing Outcome After Hematopoietic Cell Transplantation From a Partially Matched Unrelated Versus Haploidentical Donor
- ClinicalTrials.gov ID
- NCT03275636
- Acronym / sponsor ID
- HAMLET / DKMS-16-01
- Keywords
- Haploidentical, mismatched unrelated donor, hematopoietic stem cell transplantation, donor comparison
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 98 participants (actual)
- Lead sponsor
- DKMS gemeinnützige GmbHUniversity, hospital or other
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- 13 Apr 2024 (actual)
- Study completion
- 13 Apr 2024 (actual)
- First posted
- 7 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Haploidentical donor | Experimental | Biological: Peripheral blood stem cellsPeripheral blood stem cells from Haploidentical donor |
| partially matched unrelated donor | Active comparator | Biological: Peripheral blood stem cellsPeripheral 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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.
Key exclusion criteria (11 listed)
- Relapse or graft failure after a first allogeneic transplantation.
- Thymic ALL in first complete remission.
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Peripheral blood stem cellsAlso: PBSCHematopoietic stem cell transplantation with PBSC | Biological | Haploidentical donor, partially matched unrelated donor |
Primary outcome
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.
6 secondary outcomes
Engraftment rate
Time frame: day 56
Immune-reconstitution rate
Time frame: day56
Infections
Time frame: 2 months after HCT
Event Free Survival
Time frame: 1 year
Graft vs Host Disease
Time frame: 1 year
Graft vs Host Disease-free survival
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Johannes Schetelig, Prof Dr med study chair
Universtitätsklinikum Dresden
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Peripheral blood stem cells in people with AML and ALL, run by DKMS gemeinnützige GmbH at 9 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2024.