Registry and clinical trial comparing standard intensity and reduced intensity treatment in patients with AML or CLL who do not have residual disease.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medizinische Hochschule Hannover

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

19 Dec 2025 → ongoing

Decision date (initial)

2025-07-07

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

EU Funding, Programme Horizon Europe

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Diagnosis

● MRD registry, Arm A (AML):
To determine the frequency of MRD negative complete remission (CR), CR with incomplete hematologic recovery (CRi) and CR with partial hematologic recovery (CRh) in the registered cohort of AML patients with ELN intermediate risk who have been treated with standard induction chemotherapy for 1-2 cycles.

● MRD registry, Arm B (CLL):
To determine the frequency of undetectable MRD (uMRD) in treatment-naive CLL patients who have been treated with fixed duration treatments for 7 or 9 cycles, depending on the treatment regimen.

● RESOLVE trial, Arm A (AML):
To evaluate non-inferiority of non-alloHCT consolidation (group 2) compared to alloHCT consolidation (group 1) with regard to overall survival (OS) in intermediate-risk AML patients who tested MRD-negative after 1-2 cycles of induction chemotherapy.

● RESOLVE trial, Arm B (CLL):
To demonstrate a lower average overall adverse event burden score based on physician assessment during the first 6 months after randomization in patients with CLL achieving uMRD who stopped treatment at the time of randomization (treatment group 4) compared to those completing fixed-duration treatment as per standard of care (treatment group 3).

Secondary objectives 10

1. MRD registry, Arm A (AML): To assess the response rate after 1-2 cycles of chemotherapy
2. MRD registry, Arm A (AML): To identify reasons for non-participation in the RESOLVE trial
3. MRD registry, Arm B (CLL): To assess the frequency of uMRD
4. MRD registry, Arm B (CLL): To identify reasons for non-participation in the RESOLVE trial
5. RESOLVE trial, Arm A (AML): To evaluate GvHD-free-relapse-free survival (GRFS)
6. RESOLVE trial, Arm A (AML): To evaluate the cumulative incidence of relapse (CIR)
7. RESOLVE trial, Arm A (AML): To evaluate the cumulative incidence of non-relapse mortality (CID)
8. RESOLVE trial, Arm B (CLL): To assess the frequency of adverse events not considering laboratory AEs
9. RESOLVE trial, Arm B (CLL): To evaluate the duration of response
10. RESOLVE trial, Arm B (CLL): To evaluate the rate of progression-free survival

Conditions and MedDRA coding

Arm A (AML): Newly diagnosed de novo Acute myeloid leukemia (AML) or MDS/AML (MDS = Myelodysplastic syndrome) patients according to ICC 2022 or newly diagnosed AML or MDS-IB2 patients according to WHO 2022 classifications Arm B (CLL): Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Federal Institute For Drugs And Medical Devices, Paul-Ehrlich-Institut

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 43

1. RESOLVE trial, Arm A (AML): 1. Newly diagnosed de novo AML or MDS/AML patients according to ICC 2022 or newly diagnosed AML or MDS-IB2 patients according to WHO 2022 classifications. For better readability, AML, MDS/AML or MDS-IB2 patients are generally referred to as AML patients.
2. RESOLVE trial, Arm A (AML): 10. Female patient must agree not to breastfeed during treatment and for 6 months after the end of the trial-specific treatment.
3. RESOLVE trial, Arm A (AML): 11. Male patient must not donate sperm during treatment and for 6 months after the end of the trial-specific treatment.
4. RESOLVE trial, Arm A (AML): 12. Informed consent for registration in MRD registry is available and the patient is registered in the MRD registry
5. RESOLVE trial, Arm A (AML): 13. Written informed consent for randomization (in RESOLVE trial, Arm A)
6. RESOLVE trial, Arm A (AML): 14. Patient agrees not to participate in another clinical trial (other investigational drugs or devices) while participating in the RESOLVE trial
7. RESOLVE trial, Arm B (CLL): 1. Diagnosis of CLL or SLL. For better readability, CLL or SLL patients are generally referred to as "CLL patients"
8. RESOLVE trial, Arm B (CLL): 2. Patients of all genders, age ≥ 65 years at time of registration
9. RESOLVE trial, Arm B (CLL): 3. Undetectable MRD in peripheral blood according to a certified (ERIC/RESOLVE) MRD laboratory at C7D1 AND C8D1 (venetoclax + anti-CD20 MoAb (obinutuzumab)) or C9D1 AND C10D1 (venetoclax + BTKi ibrutinib). MRD negativity or uMRD prior to randomization is confirmed if MRD is undetectable at a sensitivity level of <10-4 (uMRD4 or uMRD5) at MRD1 (C7D1 or C9D1) and <10-5 (uMRD5) at MRD2 (C8D1 or C10D1).
10. RESOLVE trial, Arm B (CLL): 4. Male patient of reproductive potential and a female partner who is of childbearing potential must agree to use highly effective methods of contraception during treatment and until 6 months after the end of the assigned trial-specific treatment
11. RESOLVE trial, Arm B (CLL): 5. Female patient must agree not to breastfeed during treatment and for 18 months after the end of the assigned trial-specific treatment.
12. RESOLVE trial, Arm A (AML): 2. Intermediate risk according to ELN 2022 recommendations
13. RESOLVE trial, Arm B (CLL): 6. Male patient must not donate sperm during treatment and for 6 months after the end of the assigned trial-specific treatment.
14. RESOLVE trial, Arm B (CLL): 7. Informed consent for registration in the MRD registry is available and the patient is registered in the MRD registry
15. RESOLVE trial, Arm B (CLL): 8. Written informed consent for randomization (in the RESOLVE trial, Arm B)
16. RESOLVE trial, Arm B (CLL): 9. Patient agrees not to participate in another clinical trial (other investigational drugs or devices) while participating in the RESOLVE trial
17. RESOLVE trial, Arm A (AML): 3. AML patients who achieved CR, CR with incomplete hematologic recovery (CRi) or CR with partial hematologic recovery (CRh) after intensive induction therapy
18. RESOLVE trial, Arm A (AML): 4. AML patients who are MFC-MRD-negative (cutoff <0.1%) in bone marrow after 1 - 2 cycles of standard induction/consolidation chemotherapy according to a certified (RESOLVE) MRD laboratory; the latest assessment must be MRD-negative
19. RESOLVE trial, Arm A (AML): 5. Patients of all genders, age 18-70 years at time of registration
20. RESOLVE trial, Arm A (AML): 6. Fit for alloHCT based on investigator assessment
21. RESOLVE trial, Arm A (AML): 7. Suitable alloHCT donor available, who can be recruited within a short time frame (e.g. 4 weeks)
22. RESOLVE trial, Arm A (AML): 8. Male and female patients of reproductive potential must agree to use highly effective methods of contraception during treatment and until 6 months after the end of the assigned treatment.
23. RESOLVE trial, Arm A (AML): 9. Female patient of childbearing potential must: o Agree not to try to become pregnant during treatment and for 6 months after the end of trial-specific treatment and o have a negative urine or serum pregnancy test at screening o Unless conditions apply that exclude a pregnancy, women who have the potential to become pregnant must agree to pregnancy testing prior and during treatment in accordance with local standards.
24. MRD registry, Arm A (AML): 1. Newly diagnosed de novo AML or MDS/AML patients according to ICC 2022 or newly diagnosed AML or MDS-IB2 patients according to WHO 2022 classifications. For better readability, AML, MDS/AML or MDS-IB2 patients are generally referred to as AML patients.
25. MRD registry, Arm A (AML): 2. Patients of all genders, age 18-70 years
26. MRD registry, Arm A (AML): 3. Scheduled for or undergoing intensive induction chemotherapy according to state of the art
27. MRD registry, Arm A (AML): 4. Fit or potential to becoming fit for alloHCT
28. MRD registry, Arm A (AML): 5. Unknown ELN 2022 risk or known ELN 2022 intermediate risk
29. MRD registry, Arm A (AML): 6. Male and female patients of reproductive potential must agree to use effective methods of contraception adequate for the planned intervention and as per locally accepted standards.
30. MRD registry, Arm A (AML): 7. Unless conditions apply that exclude a pregnancy, women who have the potential to become pregnant must consent to undergo pregnancy testing prior to treatment in accordance with local standards. If necessary, they must also agree to additional testing throughout the treatment period.
31. MRD registry, Arm A (AML): 8. Able to understand and willing to sign an informed consent form (ICF)
32. MRD registry, Arm A (AML): 9. Written informed consent for registration
33. MRD registry, Arm A (AML): 10. Patient agrees not to participate in another clinical trial (other investigational drugs or devices) before randomization
34. MRD registry, Arm B (CLL): 1. Diagnosis of CLL or small lymphocytic lymphoma (SLL) For better readability, “CLL or SLL patients” are generally referred to as “CLL patients”.
35. MRD registry, Arm B (CLL): 2. Treatment naïve CLL/SLL or undergoing first line treatment during the first 4 months of treatment
36. MRD registry, Arm B (CLL): 3. Patient of all genders, age ≥ 65 years
37. MRD registry, Arm B (CLL): 4. Active disease requiring treatment as per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria
38. MRD registry, Arm B (CLL): 5. Scheduled for or undergoing treatment with a fixed-duration regimen
39. MRD registry, Arm B (CLL): 6. Known immunophenotype of CLL cells that is suitable for MRD assessment (as determined in MRD assessment at registration by national MRD reference laboratory)
40. MRD registry, Arm B (CLL): 7. Male patients of reproductive potential must agree to use effective methods of contraception adequate for the planned intervention and as per locally accepted standards.
41. MRD registry, Arm B (CLL): 8. Able to understand and willing to sign an informed consent form (ICF)
42. MRD registry, Arm B (CLL): 9. Written informed consent for registration
43. MRD registry, Arm B (CLL): 10. Patient agrees not to participate in another clinical trial (other investigational drugs or devices) before randomization

Exclusion criteria 23

1. RESOLVE trial, Arm A (AML): 1. ELN 2022 favorable or adverse risk AML
2. RESOLVE trial, Arm B (CLL): 1. Patients with relapsed/refractory CLL
3. RESOLVE trial, Arm B (CLL): 2. Patients with atypical immunophenotype not suitable for MRD assessment (as determined in MRD assessment at registration by national reference laboratory)
4. RESOLVE trial, Arm B (CLL): 3 CLL with del(17p) and/or mutated TP53
5. RESOLVE trial, Arm B (CLL): 4. Medical condition that interferes with a patient’s ability to give informed consent
6. RESOLVE trial, Arm B (CLL): 5. Participation in another clinical trial (other investigational drugs or devices) at the time the CLL patient starts the fixed-duration regime or within 14 days prior to it.
7. RESOLVE trial, Arm A (AML): 2. Treatment with a hypomethylating agent (with or without venetoclax)
8. RESOLVE trial, Arm A (AML): 3. Prior myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) or CML or MDS/MPN
9. RESOLVE trial, Arm A (AML): 4. Acute promyelocytic leukemia (APL) with t(15;17)(q22;q12); PML-RARA, or other translocations associated with APL
10. RESOLVE trial, Arm A (AML): 5. AML with FLT3-ITD with either high allelic ratio (>0.5) or high variant allele frequency (VAF) >33% with NPM1 wildtype at initial diagnosis
11. RESOLVE trial, Arm A (AML): 6. AML with known BCR-ABL1
12. RESOLVE trial, Arm A (AML): 7. Medical condition that interferes with a patient’s ability to give informed consent
13. RESOLVE trial, Arm A (AML): 8. Medical or psychological condition that precludes undergoing alloHCT
14. RESOLVE trial, Arm A (AML): 9. Participation in another clinical trial (other investigational drugs or devices) at the time the AML patient starts the (induction) chemotherapy or within 14 days prior to it.
15. MRD registry, Arm A (AML): 1. Prior myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) or CML or MDS/MPN
16. MRD registry, Arm A (AML): 2. Acute promyelocytic leukemia (APL) with t(15;17)(q22;q12); PML-RARA, or other translocations associated with APL
17. MRD registry, Arm A (AML): 3. Known ELN 2022 favorable or adverse risk
18. MRD registry, Arm A (AML): 4. Pregnant or lactating woman
19. MRD registry, Arm A (AML): 5. Medical condition that interferes with a patient’s ability to give informed consent
20. MRD registry, Arm B (CLL): 1. Relapsed/refractory CLL after prior treatments
21. MRD registry, Arm B (CLL): 2. Patients with atypical immunophenotype not suitable for MRD assessment (as determined in MRD assessment at registration by national reference laboratory)
22. MRD registry, Arm B (CLL): 3. CLL with del(17p) and/or mutated TP53
23. MRD registry, Arm B (CLL): 4. Medical condition that interferes with a patient’s ability to give informed consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. MRD registry, Arm A (AML): Frequency of MRD negative CR/CRi/CRh in AML patients after 1-2 cycles with standard induction therapy.
2. MRD registry, Arm B (CLL): Frequency of uMRD at first on-treatment MRD assessment (VEN + anti-CD20 MoAb: C7D1 after treatment start; VEN + BTKi ibrutinib: C9D1 after treatment start)
3. RESOLVE trial, Arm A (AML): Overall survival (OS)
4. RESOLVE trial, Arm B (CLL): Average overall adverse event burden score based on physician assessment during the period from randomization to AE score 03 assessment (C14D1 for venetoclax + moAB treated patients; C16D1 for venetoclax + BTKi ibrutinib treated patients).

Secondary endpoints 13

1. MRD registry, Arm A (AML): Rate of CR defined by ELN 2022 after 1-2 cycles of chemotherapy.
2. MRD registry, Arm A (AML): Rate of CR with incomplete hematologic recovery (CRi) rate defined by ELN 2022 after 1-2 cycles of chemotherapy.
3. MRD registry, Arm A (AML): Rate of CR with partial hematologic recovery (CRh) rate defined by ELN 2022 after 1-2 cycles of chemotherapy.
4. MRD registry, Arm A (AML): Rate of morphologic leukemia-free state (MLFS) defined by ELN 2022 after 1-2 cycles of chemotherapy.
5. MRD registry, Arm A (AML): Frequency of reasons for non-participation in the RESOLVE trial.
6. MRD registry, Arm B (CLL): Rate of uMRD in peripheral blood at the time of MRD1 and MRD2 assessments.
7. MRD registry, Arm B (CLL): Frequency of reasons for non-participation in the RESOLVE trial.
8. RESOLVE trial, Arm A (AML): GvHD-free-relapse-free survival (GRFS) in groups 1 and 2 measured from the date of randomization until the date of hematologic relapse or death from any cause or grade III–IV acute GvHD or chronic GVHD that requires systemic treatment
9. RESOLVE trial, Arm A (AML): Cumulative incidence of relapse (CIR) in groups 1 and 2 measured from the date of achievement of a remission until the date of hematologic relapse; patients not known to have relapsed are censored on the date they were last assessed for response; death without relapse will be considered as competing event.
10. RESOLVE trial, Arm A (AML): Cumulative incidence of non-relapse mortality (CID) in groups 1 and 2 defined as death in CR/CRi/CRh/MLFS and measured from randomization to death with relapse as a competing event. Patients who are not known to have relapsed or died will be censored at the date of last response assessment.
11. RESOLVE trial, Arm B (CLL): Average overall adverse event burden score based on physician assessment excluding laboratory AEs from randomization to AE score 3 assessment (C14D1 for venetoclax + moAb treated patients; C16D1 for venetoclax + BTKi ibrutinib treated patients).
12. RESOLVE trial, Arm B (CLL): Duration of response (DOR) measured from randomization to the date that disease progression is objectively documented or death, whichever occurs first.
13. RESOLVE trial, Arm B (CLL): 3-year progression-free survival (PFS) measured from randomization until the date of disease progression or death from any cause.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 11

Comparator 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medizinische Hochschule Hannover

Sponsor organisation

Medizinische Hochschule Hannover

Address

Carl-Neuberg-Strasse 1, Gross Buchholz Gross Buchholz

City

Hanover

Postcode

30625

Country

Germany

Scientific contact point

Organisation

Medizinische Hochschule Hannover

Contact name

Prof. Dr. med. Michael Heuser

Public contact point

Organisation

Medizinische Hochschule Hannover

Contact name

Prof. Dr. med. Michael Heuser

Third parties 8

Locations

3 EU/EEA countries · 40 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 54 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications