Newly Diagnosed
International phase 2 randomised controlled trial comparing venetoclax-low dose cytarabine with standard intensive chemotherapy in newly diagnosed NPM1-mutated AML.
Key Inclusion criteria
- Age ≥50
- Fit for intensive therapy
- NPM1 mutated FLT3-ITD negative
- CD33 positive acute myeloid leukemia
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
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- Multiple
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
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- 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.
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- 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.
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- 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
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
Phase 3, Double-Blind, Randomised, Placebo-Controlled Trial Of Quizartinib or Placebo Plus Chemotherapy in Newly Diagnosed Patients With FLT3-ITD Negative AML.
Key Inclusion criteria
- Age ≥ 18 years and ≤70
- Newly diagnosed, morphologically documented primary AML based on World Health Organization (WHO) 2016 classification
- ECOG performance status 0-2.
- Patient fit for standard "7+3" induction chemotherapy regimen
Key Exclusion criteria
- Acute promyelocytic leukemia (APL), or BCR-ABL positive leukaemia
- AML secondary to prior chemotherapy or radiotherapy.
- AML with known antecedent MDS, MPN or MDS/MPNs including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (aCML), juvenile myelomonocytic leukemia (JMML) and others.
- Newly diagnosed AML with FLT3-ITD mutations ≥5% VAF (or ≥0.05 SR) based on a validated FLT3 mutation assay.
Sites open
- Queen Elizabeth Hospital Birmingham, King's College Hospital, Hammersmith Hospital, Maidstone, Manchester Royal Infirmary, Oxford, Torquay
Relapse/Refractory
Phase 1/2 study of the menin inhibitor bleximenib in relapsed/refractory (R/R) NPM1 mutated or KMT2A rearranged AML.
Key Inclusion criteria
- R/R AML with either NPM1-mutation or KMT2A-rearrangement
Sites open
- Cardiff, The Christie, Liverpool, Guys & St Thomas', Leeds, Oxford, Plymouth, UCLH
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
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
- 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
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- Cardiff, The Royal Marsden, Guys & St Thomas'
Phase 1/2 study of a CD33xVδ2 T-Cell Engager for Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Neoplasms.
Key Inclusion criteria
- Age ≥18
- Relapsed/refractory acute myeloid leukemia (AML) or relapsed/refractory moderate high, high, or very high risk IPSS-M myelodysplastic neoplasms (MDS)
- eGFR ≥40 mL/min, ECOG 0-2
Key Exclusion criteria
- Corticosteroids >10 mg daily prednisone equivalents, autoimmune disease that requires systemic immunosuppressive medications
- AlloHSCT within 3 months
- Uncontrolled systemic viral, bacterial, or fungal infection
- Active CNS involvement
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- Cambridge, UCLH, The Christie
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
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
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- Queen Elizabeth Hospital Birmingham, Cardiff, Glasgow, Hammersmith Hospital, Newcastle, Oxford, Sheffield
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
BioDrive seeks to identify the most effective way to prevent and detect fungal infection in patients with acute leukaemia (acute myeloid leukaemia, acute lymphoblastic leukaemia, high-risk myelodysplastic syndromes and transformed myeloproliferative neoplasms); assessing if monitoring the risk of fungal infection by regular blood tests is safe and reduces the need to use antifungal drugs.
Key Inclusion criteria
- Age ≥16 years
- Diagnosis of new, or relapsed, acute leukaemia or haematological disorder judged to need chemotherapy by the patient’s clinical care team, including AML, ALL, HRMDS, or AML transformation of a myeloproliferative neoplasm (tMPN).
- Patient expected to have prolonged neutropenia related to chemotherapy which would mandate either antifungal prophylaxis and/or systematic invasive fungal infection biomarker monitoring (at least weekly).
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
Contact
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- Multiple
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
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- Multiple