MITOXANTRONE HYDROCHLORIDE for Acute myeloid leukemia (AML) | Chronic lymphocytic leukemia (CLL) | Myelodysplastic syndrome (MDS) | Small lymphocytic lymphoma (SLL)

Inclusion criteria

• {"criterion_text":"- 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.\n- 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\n- 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.\n- RESOLVE trial, Arm A (AML): 2. Intermediate risk according to ELN 2022 recommendations\n- 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.\n- 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\n- RESOLVE trial, Arm B (CLL): 8. Written informed consent for randomization (in the RESOLVE trial, Arm B)\n- 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\n- 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\n- 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\n- RESOLVE trial, Arm A (AML): 5. Patients of all genders, age 18-70 years at time of registration\n- 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.\n- RESOLVE trial, Arm A (AML): 6. Fit for alloHCT based on investigator assessment\n- RESOLVE trial, Arm A (AML): 7. Suitable alloHCT donor available, who can be recruited within a short time frame (e.g. 4 weeks)\n- 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.\n- RESOLVE trial, Arm A (AML): 9. Female patient of childbearing potential must: o\tAgree not to try to become pregnant during treatment and for 6 months after the end of trial-specific treatment and o\thave a negative urine or serum pregnancy test at screening o\tUnless 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.\n- 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.\n- MRD registry, Arm A (AML): 2. Patients of all genders, age 18-70 years\n- MRD registry, Arm A (AML): 3. Scheduled for or undergoing intensive induction chemotherapy according to state of the art\n- MRD registry, Arm A (AML): 4. Fit or potential to becoming fit for alloHCT\n- MRD registry, Arm A (AML): 5. Unknown ELN 2022 risk or known ELN 2022 intermediate risk\n- 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.\n- 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.\n- 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.\n- MRD registry, Arm A (AML): 8. Able to understand and willing to sign an informed consent form (ICF)\n- MRD registry, Arm A (AML): 9. Written informed consent for registration\n- MRD registry, Arm A (AML): 10. Patient agrees not to participate in another clinical trial (other investigational drugs or devices) before randomization\n- 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”.\n- MRD registry, Arm B (CLL): 2. Treatment naïve CLL/SLL or undergoing first line treatment during the first 4 months of treatment\n- MRD registry, Arm B (CLL): 3. Patient of all genders, age ≥ 65 years\n- MRD registry, Arm B (CLL): 4. Active disease requiring treatment as per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria\n- MRD registry, Arm B (CLL): 5. Scheduled for or undergoing treatment with a fixed-duration regimen\n- 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)\n- RESOLVE trial, Arm A (AML): 12. Informed consent for registration in MRD registry is available and the patient is registered in the MRD registry\n- 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.\n- MRD registry, Arm B (CLL): 8. Able to understand and willing to sign an informed consent form (ICF)\n- MRD registry, Arm B (CLL): 9. Written informed consent for registration\n- MRD registry, Arm B (CLL): 10. Patient agrees not to participate in another clinical trial (other investigational drugs or devices) before randomization\n- RESOLVE trial, Arm A (AML): 13. Written informed consent for randomization (in RESOLVE trial, Arm A)\n- 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\n- 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\"\n- RESOLVE trial, Arm B (CLL): 2. Patients of all genders, age ≥ 65 years at time of registration\n- 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)."}

Exclusion criteria

• {"criterion_text":"- RESOLVE trial, Arm A (AML): 1. ELN 2022 favorable or adverse risk AML\n- 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\n- RESOLVE trial, Arm A (AML): 6. AML with known BCR-ABL1\n- RESOLVE trial, Arm A (AML): 7. Medical condition that interferes with a patient’s ability to give informed consent\n- RESOLVE trial, Arm A (AML): 8. Medical or psychological condition that precludes undergoing alloHCT\n- 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.\n- MRD registry, Arm A (AML): 1. Prior myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) or CML or MDS/MPN\n- MRD registry, Arm A (AML): 2. Acute promyelocytic leukemia (APL) with t(15;17)(q22;q12); PML-RARA, or other translocations associated with APL\n- MRD registry, Arm A (AML): 3. Known ELN 2022 favorable or adverse risk\n- MRD registry, Arm A (AML): 4. Pregnant or lactating woman\n- MRD registry, Arm A (AML): 5. Medical condition that interferes with a patient’s ability to give informed consent\n- RESOLVE trial, Arm B (CLL): 1. Patients with relapsed/refractory CLL\n- MRD registry, Arm B (CLL): 1. Relapsed/refractory CLL after prior treatments\n- 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)\n- MRD registry, Arm B (CLL): 3. CLL with del(17p) and/or mutated TP53\n- MRD registry, Arm B (CLL): 4. Medical condition that interferes with a patient’s ability to give informed consent\n- 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)\n- RESOLVE trial, Arm B (CLL): 3 CLL with del(17p) and/or mutated TP53\n- RESOLVE trial, Arm B (CLL): 4. Medical condition that interferes with a patient’s ability to give informed consent\n- 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.\n- RESOLVE trial, Arm A (AML): 2. Treatment with a hypomethylating agent (with or without venetoclax)\n- RESOLVE trial, Arm A (AML): 3. Prior myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) or CML or MDS/MPN\n- RESOLVE trial, Arm A (AML): 4. Acute promyelocytic leukemia (APL) with t(15;17)(q22;q12); PML-RARA, or other translocations associated with APL"}

Primary endpoints

• {"endpoint_text":"- MRD registry, Arm A (AML): Frequency of MRD negative CR/CRi/CRh in AML patients after 1-2 cycles with standard induction therapy.","definition_or_measurement_approach":"Frequency of MRD negative complete remission (CR), CR with incomplete hematologic recovery (CRi) and CR with partial hematologic recovery (CRh) after 1-2 cycles of standard induction therapy; MRD assessed by MFC-MRD in bone marrow (cutoff <0.1%) in certified RESOLVE MRD laboratories."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Undetectable MRD (uMRD) in peripheral blood per certified (ERIC/RESOLVE) MRD laboratory at specified on-treatment timepoints (C7D1 and C8D1 for venetoclax+anti-CD20; C9D1 and C10D1 for venetoclax+BTKi). Sensitivity requirements specified (<10^-4 at MRD1 and <10^-5 at MRD2 for confirmation)."}
• {"endpoint_text":"- RESOLVE trial, Arm A (AML): Overall survival (OS)","definition_or_measurement_approach":"Overall survival measured from randomization to death from any cause."}
• {"endpoint_text":"- 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).","definition_or_measurement_approach":"Average overall AE burden score based on physician assessment between randomization and AE score 03 assessment at specified assessment visits (C14D1 for VEN+moAb; C16D1 for VEN+BTKi). Laboratory AEs may be excluded per endpoint definition (see protocol)."}

Secondary endpoints

• {"endpoint_text":"- MRD registry, Arm A (AML): Rate of CR defined by ELN 2022 after 1-2 cycles of chemotherapy.","definition_or_measurement_approach":"CR rate as defined by ELN 2022, assessed after 1-2 cycles of chemotherapy."}
• {"endpoint_text":"- MRD registry, Arm A (AML): Rate of CR with incomplete hematologic recovery (CRi) rate defined by ELN 2022 after 1-2 cycles of chemotherapy.","definition_or_measurement_approach":"CRi rate defined per ELN 2022 after 1-2 cycles."}
• {"endpoint_text":"- MRD registry, Arm A (AML): Rate of CR with partial hematologic recovery (CRh) rate defined by ELN 2022 after 1-2 cycles of chemotherapy.","definition_or_measurement_approach":"CRh rate as defined by ELN 2022 after 1-2 cycles."}
• {"endpoint_text":"- MRD registry, Arm A (AML): Rate of morphologic leukemia-free state (MLFS) defined by ELN 2022 after 1-2 cycles of chemotherapy.","definition_or_measurement_approach":"MLFS rate per ELN 2022 after 1-2 cycles."}
• {"endpoint_text":"- MRD registry, Arm A (AML): Frequency of reasons for non-participation in the RESOLVE trial.","definition_or_measurement_approach":"Descriptive frequency analysis of reasons recorded for non-participation in the randomized RESOLVE trial among registry-eligible patients."}
• {"endpoint_text":"- MRD registry, Arm B (CLL): Rate of uMRD in peripheral blood at the time of MRD1 and MRD2 assessments.","definition_or_measurement_approach":"uMRD rates in peripheral blood at predefined MRD1 and MRD2 assessment timepoints per certified MRD labs and sensitivity cut-offs."}
• {"endpoint_text":"- MRD registry, Arm B (CLL): Frequency of reasons for non-participation in the RESOLVE trial.","definition_or_measurement_approach":"Descriptive analysis of documented reasons for non-participation in the randomized RESOLVE trial among registry patients."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"GRFS measured from randomization until hematologic relapse, death, grade III-IV acute GvHD, or chronic GVHD requiring systemic therapy; patients censored at last response assessment if status unknown."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"CIR measured from date of remission to hematologic relapse with death without relapse as competing event; censoring rules as stated."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"CID measured from randomization to death in remission; relapse considered competing event; censoring at last response assessment."}
• {"endpoint_text":"- 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).","definition_or_measurement_approach":"Physician-assessed overall AE burden excluding laboratory AEs between randomization and AE score 3 assessment at specified visits depending on regimen."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"DOR measured from randomization to objective documentation of progression or death."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"3-year PFS measured from randomization to progression or death."}

France

Earliest CTIS Part Ii Submission Date

26-05-2025

Latest Decision Or Authorization Date

07-07-2025

Processing Time Days

42

Number Of Sites

6

Number Of Participants

52

Germany

Earliest CTIS Part Ii Submission Date

23-02-2026

Latest Decision Or Authorization Date

09-03-2026

Processing Time Days

14

Number Of Sites

25

Number Of Participants

161

Poland

Earliest CTIS Part Ii Submission Date

28-01-2026

Latest Decision Or Authorization Date

07-03-2026

Processing Time Days

38

Number Of Sites

9

Number Of Participants

76

Primary sponsor

Full Name

Medizinische Hochschule Hannover

Organisation Type

Educational Institution

Country Of Registered Address

Germany

Third parties

• {"country":"Greece","full_name":"Centre for Research and Technology Hellas (CERTH)","duties_or_roles":"codes: 10","organisation_type":"Educational Institution"}
• {"country":"Italy","full_name":"IRCCS - Ospedale San Raffaele","duties_or_roles":"codes: 4","organisation_type":"Health care"}
• {"country":"Germany","full_name":"Medizinische Hochschule Hannover","duties_or_roles":"codes: 12,5,6,8","organisation_type":"Educational Institution"}
• {"country":"France","full_name":"CHU de Tours - Hopital Bretonneau","duties_or_roles":"codes: 1,13,2,5","organisation_type":"Health care"}
• {"country":"Italy","full_name":"Università Tor Vergata di Roma","duties_or_roles":"codes: 4","organisation_type":"Educational Institution"}
• {"country":"United Kingdom","full_name":"St James's University Hospital","duties_or_roles":"codes: 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Deutsches Krebsforschungszentrum Stiftung Des Oeffentlichen Rechts","duties_or_roles":"codes: 10","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Netherlands","full_name":"Amsterdam UMC Stichting","duties_or_roles":"codes: 4","organisation_type":"Patient organisation/association"}