Newly Diagnosed
International phase 3 randomised controlled trial comparing intensive treatment strategies for newly diagnosed FLT3-mutated AML.
Learn more about OPTIMISE-FLT3
Key Inclusion criteria
- Age ≥16
- Fit for intensive therapy
- FLT3-ITD or FLT3-TKD mutated
- New presentations requiring emergency treatment can be enrolled prior to FLT3 result
Key Exclusion criteria
- Receipt of any previous therapy for AML or any antecedent haematological condition (the use of oral hydroxycarbamide to control white blood cell count is permitted)
- Other active malignancy requiring treatment
- Blast transformation of chronic myeloid leukaemia (CML)
Contact
Sites open
- Multiple
International phase 3 randomised trial of newly diagnosed patients ineligible for intensive chemotherapy with IDH1m AML using ivosidenib plus azacitidine ± venetoclax.
Key Inclusion criteria
- Patients with newly diagnosed IDH1-mutated AML or MDS/AML according to the 2022 International Consensus Classification.
- Age ≥ 18 years, no upper age limit.
- Ineligible for intensive induction chemotherapy by meeting at least 1 of the following criteria:
- ≥ 75 years of age ineligible for intensive chemotherapy per physician’s discretion (ECOG PS 0-2).
- 18-74 years: not eligible for standard chemotherapy with any of the following co-morbidities:
- ECOG PS 2 or 3.
- Cardiac history of chronic heart failure requiring treatment; or with an ejection fraction ≤50%; or chronic stable angina.
- DLCO ≤ 65% or FEV1 ≤ 65%.
- Creatinine clearance ≥ 30 mL/min to <45 ml/min calculated by the Cockcroft Gault formula.
- Moderate hepatic impairment with total bilirubin > 1.5 to < 3.0 x upper limit of normal (ULN).
Key Exclusion criteria
- Previous AML treatment except hydroxyurea to control WBC counts. ESA or luspatercept for MDS is allowed. Prior hypomethylating agent for MDS-EB is not allowed.
- AML with BCR-ABL1; or myeloid blast crisis of CML.
Sites open
- Multiple
International phase 3 randomised trial of newly diagnosed patients ineligible for intensive chemotherapy with either NPM1m or KMT2Ar AML 1:1 to venetoclax plus-azacitidine ± revumenib (menin inhibitor).
Key Inclusion criteria
- Patients with newly diagnosed NPM1-mutated or KMT2A-rearranged AML or MDS/AML according to the 2022 International Consensus Classification.
- Age ≥ 18 years, no upper age limit.
- Ineligible for intensive induction chemotherapy by meeting at least 1 of the following criteria:
- ≥ 75 years of age ineligible for intensive chemotherapy per physician’s discretion (ECOG PS 0-2).
- 18-74 years: not eligible for standard chemotherapy with any of the following co-morbidities:
- ECOG PS 2 or 3.
- Cardiac history of chronic heart failure requiring treatment; or with an ejection fraction ≤50%; or chronic stable angina.
- DLCO ≤ 65% or FEV1 ≤ 65%.
- Creatinine clearance ≥ 30 mL/min to <45 ml/min calculated by the Cockcroft Gault formula.
- Moderate hepatic impairment with total bilirubin > 1.5 to < 3.0 x upper limit of normal (ULN).
Key Exclusion criteria
- Previous AML treatment except hydroxyurea to control WBC counts. ESA or luspatercept for MDS is allowed. Prior hypomethylating agent for MDS-EB is not allowed.
- AML with BCR-ABL1; or myeloid blast crisis of CML.
Sites open
- Multiple
Phase 2 trial assessing oral azacitidine and venetoclax in newly diagnosed AML unfit for intensive therapy.
Key Inclusion criteria
- Age >75 or <75 with comorbidity/ ECOG 2
Sites open
- King's College Hospital, The Christie
International phase 3 randomised placebo-controlled trial assessing ziftomenib in combination with intensive therapy or Venetoclax-Azacitidine in patients with untreated NPM1 mutated or KMT2A-rearranged acute myeloid leukaemia.
Key Inclusion criteria
- Patients with newly diagnosed NPM1-mutated or KMT2A-rearranged AML
- Intensive arm: Newly diagnosed NPM1-mutated or KMT2A-rearranged AML
- Non-intensive arm: Newly diagnosed NPM1-mutated AML
Sites open
- Barts, Guys & St Thomas', Leeds, St George's, Wolverhampton
Phase 3 Randomised, Double-blind, Placebo-controlled, Study of Bleximenib, Venetoclax and Azacitidine for with untreated NPM1 mutated or KMT2A-rearranged acute myeloid leukaemia ineligible for Intensive Chemotherapy.
Key Inclusion criteria
- Patients with newly diagnosed NPM1-mutated or KMT2A-rearranged AML Ineligible for Intensive Chemotherapy
Sites open
- Brighton, Cambridge, Canterbury, Colchester, Edinburgh, Liverpool, Guys & St Thomas', Plymouth, Worthing
International phase 3 randomised placebo-controlled trial assessing revumenib in combination with intensive therapy in patients with untreated NPM1 mutated acute myeloid leukaemia.
Key Inclusion criteria
- Patients fit for intensive chemotherapy with newly diagnosed NPM1-mutated AML
Sites open
- Oxford, Aberdeen, Derby, Lincoln, Hammersmith Hospital, Royal Marsden
Relapse/Refractory
Phase 1/2 study of the menin inhibitor enzomenib in relapsed/refractory (R/R) NPM1 mutated or KMT2A rearranged AML.
Key Inclusion criteria
- R/R AML blasts >5% with NPM1m, KMT2Ar, TP53m, NUP98, UBTF-TD
Sites open
- Queen Elizabeth Hospital Birmingham, The Christie, Oxford, Kings' College Hospital, Guys & St Thomas' Hospital, UCLH
Phase 1 study to investigate the safety and efficacy of APL-4098 alone, and in combination with azacitidine or azacitidine and venetoclax in AML and MDS/AML.
Key Inclusion criteria
- Age ≥18
- ND or R/R AML (primary or secondary, including treatment-related), participant is intolerant to, or considered ineligible for available therapies known to provide clinical benefit. Must have ≥5% blasts in BM or ≥1% blasts in the peripheral blood.
- MDS/AML defined as diagnosis of MDS with 10-19% BM blasts who have not had a response after at least four cycles of treatment with a monotherapy hypomethylating agent (HMA)
- MDS with 5%-9% bone marrow blasts who are not benefiting with monotherapy hypomethylating agents (Phase 1 only; MDS-EB patients will not be enrolled in the Phase 2 part of the study)
Key Exclusion criteria
- Allogenenic transplant within 6 months of screening
Sites open
- Cardiff, The Royal Marsden, Guys & St Thomas', Glasgow
Phase 1/2 study of AZD3632 Monotherapy or in Combination With Anticancer Agents in Participants With Advanced Haematologic Malignancies With KMT2Ar, NPM1m, or Other Genotypes Associated With HOX Overexpression
Key Inclusion criteria
- /R AML blasts >5% with NPM1m, KMT2Ar, KMT2A-PTD, other menin-dependent mutations/translocations
Key Exclusion criteria
- Active CNS involvement
Sites open
- The Christie, Kings' College Hospital, UCLH
Phase 1 study of BCL2 degrader.
Learn more about JNJ-95804306/EDI1001
Key Inclusion criteria
- R/R AML
Key Exclusion criteria
- Previous proven or probable invasive fungal infection (IFI) (according to the EORTC/MSG criteria). (I.e. this would not include previously treated cutaneous or other non-invasive infection, etc. If there is doubt about eligibility, please discuss with the local PI / research team and, if required, the central trial team / Chief Investigators).
- Contraindication to all potential prophylactic antifungal agents (i.e. cannot be prescribed any recognised anti-Aspergillus agent as prophylaxis)
- Planned chemotherapy using any regimen that mandates the use of systemic antifungal medication
Sites open
- Christie, UCLH, Royal Marsden
Transplant Related
MO-TRANS is a randomised multi-centre phase 3 trial of mocravimod maintenance treatment post allogeneic stem cell transplant.
Key Inclusion criteria
- AML according to WHO 2022 classification
- ELN high-risk or intermediate-risk in CR1, any risk AML in CR2
- Planned allogeneic transplant from 9/10-10/10 HLA-matched donor or haploidentical donor with use of PBSC graft
- Any conditioning regime with a Transplant conditioning Score (TCI) ≥ 1.5
- Use of Tacrolimus-based GVHD prophylaxis
- Age ≥18 and ≤75
Key Exclusion criteria
- Use of ciclosporin, anti-thymocyte globulin (ATG), alemtuzumab or abatacept for GVHD prophylaxis
- Macular oedema
Sites open
- Queen Elizabeth Hospital Birmingham, Cardiff, Glasgow, Imperial College London, Newcastle, Oxford, Sheffield, Manchester Royal Infirmary, UCLH
Phase 1/2 study assessing granulocyte augmentation to single-cord blood transplantation for high risk AML.
Key Inclusion criteria
- Fit, transplant-eligible patients, aged <55
- High risk AML or MDS/AML (as defined by ICC 2022) fitting one or more of the following criteria:
- -TP53 mutation (single- or multi-hit)
- -Presence of inv(3) (q21.3q26.2) or t(3;3)(q21.3;q26.2)
- -Adverse risk (as per ICC 2022) and >0.1% MRD by flow cytometry after 2 cycles of induction
- -AML (any risk) with partial remission (<10% blasts) after 2 cycles induction
- -Early relapse (<6 months) after chemotherapy alone (excluding t(16;16), inv(16) or t(8;21))
- Bone marrow performed within 28 days of starting conditioning chemotherapy demonstrates either:
a. <10% blasts
b. >10% blasts with a hypocellular background (must be discussed with the trial team)
c. FEV1 >65% without dyspnoea on mild activity
d. AST/ALT <3 x ULN
e. Bilirubin <1.5 x ULN (excluding Gilbert’s syndrome)
f. Performance Status (ECOG) of 0 or 1
Key Exclusion criteria
- AML secondary to a myeloproliferative neoplasm
- Active CNS disease
- Prior allogeneic stem cell transplant
Contact
Sites open
- Kings' College Hospital, The Christie, The Royal Marsden
Supportive Care
PROPEL is a multicentre randomised controlled trial comparing best practice usual care (BPUC) with a personalised prehabilitation care package (PPCP) incorporating a 12-month internal pilot, parallel process evaluation and economic evaluation.
Key Inclusion criteria
- Age ≥ 16 years, treated on adult AML pathway
- Diagnosis of either AML or MDS-EB2 (MDS with ≥10% blasts in the bone marrow) following first diagnosis or disease relapse
- In complete morphological remission (defined <5% blasts in bone marrow)
- Planned to receive either:
- Intensive treatment (e.g. anthracycline/cytarabine based chemotherapy and/or HSCT), or lower intensity treatment (i.e. Venetoclax based treatment) with HSCT – Pathway 1
- Or
- Planned to receive lower intensity treatment without HSCT (e.g. Venetoclax or Ivosidenib based treatment)- Pathway 2
- Prior to, or within the 1st course of treatment following remission
- Planned to receive at least one further full cycle of treatment (chemotherapy or HSCT) post randomisation
- Access to the internet and an email address
- Willing to use videoconferencing to undertake the appointments and sessions
Key Exclusion criteria
- Diagnosis of Acute Promyelocytic Leukaemia
- Undergoing single agent Azacitidine, single agent low dose Cytarabine, Menin inhibitors or FLT3 inhibitor treatment without planned HSCT
Contact
Sites open
- Multiple