Authorised Phase I and Phase II (Integrated)- Other Acute Myeloid Leukemia (AML)

A clinical trial to evaluate the safety and effectiveness of a combination of either AG-12or AG-221 tablets with azacitidine injections in patients withnewly diagnosed Acute Myeloid Leukemia (AML) and who have mutations in enzymes isocitrate dehydrogenase 1 or 2 (IDH 1 or IDH2) and are not candidates to receive intensive induction chemotherapy.

EU CTIS ID: 2024-511722-31-00

What this study is testing

Ph Ib Dose Finding Stage: - To assess the safety and tolerability of the combination treatments of oral AG-120 when administered with subcutaneous (SC) azacitidine and oral AG-221 when administered with SC azacitidine in subjects with newly diagnosed AML with an IDH1 or an IDH2 mutation, respectively, who are not candidates to receive intensive IC. - To establish the recommended combination dose (RCD) of oral AG-120 and oral AG-221 when administered with SC azacitidine. Ph Ib AG-120 Expansion Stage:- To assess the safety and tolerability of the combination treatments of oral AG-120 when administered with SC azacitidine in subjects with newly diagnosed AML with an IDH1 mutation who are not candidates to receive intensive IC. Ph II AG-221 Randomized Stage: - To assess the efficacy of oral AG-221 when administered with SC azacitidine versus SC azacitidine alone in subjects with newly diagnosed AML with an IDH2 mutation, who are not candidates to receive intensive IC.

  • Phase I and Phase II (Integrated)- Other

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

  • 1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
  • 2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
  • 3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
  • 4. Subject has newly diagnosed, primary (ie, de novo) or secondary (progression of MDS or myeloproliferative neoplasms [MPN], or therapyrelated) AML according to the WHO classification (Appendix B) with ≥ 20% leukemic blasts in the bone marrow: a. Have an IDH1 or IDH2 gene mutation (R132, R140, or R172) - IDH mutational status will be assessed locally; for sites without local testing capabilities, a referral lab will be identified. b. By the investigator's assessment who are not candidates to receive intensive IC.
  • 5. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (Appendix D).
  • 6. Subject has adequate organ function defined as: - Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 3 x ULN, unless considered due to leukemic organ involvement. - Serum total bilirubin < 1.5 x ULN. Higher levels are acceptable if these can be attributed to ineffective erythropoiesis, ≤3 times the upper limit of normal for Gilbert's syndrome (eg, a gene mutation in UGT1A1), or leukemic organ involvement. - Serum creatinine < 2 x ULN or creatinine clearance > 30 mL/min based on the Modification of Diet in Renal Disease (MDRD) glomerular filtration rate (GFR): GFR (mL/min/1.73 m2) = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if African American)

You likely can't join if

  • 1. Subject is suspected or proven to have acute promyelocytic leukemia based onmorphology, immunophenotype, molecular assay, or karyotype (Appendix B).
  • 10. Subject is known seropositive for or has active viral infection with human immunodeficiency virus (HIV), or active infection with hepatitis Bvirus (HBV) or hepatitis C virus (HCV)
  • 11. Subject is known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally
  • 12. Subject has uncontrolled hypertension (systolic blood pressure [BP] > 180 mmHg or diastolic BP > 100 mmHg)
  • 13. Subject is taking the following sensitive CYP substrate medications that have a narrow therapeutic range are excluded from the study unless the subject can be transferred to other medications at least 5 half-lives prior to the start of study treatment: phenytoin(CYP2C9), S-mephenytoin (CYP2C19), thioridazine (CYP2D6), theophylline, and tizanidine (CYP1A2) (Appendix K).
  • 14. Subject is taking the breast cancer resistance protein (BCRP) transporter-sensitive substrate rosuvastatin; subject should be excluded from the study unless he/she can be transferred to other medications at least 5 half-lives prior to the start of study treatment (Appendix L).
See the full eligibility criteria
Who can join
  • 1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
  • 2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
  • 3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
  • 4. Subject has newly diagnosed, primary (ie, de novo) or secondary (progression of MDS or myeloproliferative neoplasms [MPN], or therapyrelated) AML according to the WHO classification (Appendix B) with ≥ 20% leukemic blasts in the bone marrow: a. Have an IDH1 or IDH2 gene mutation (R132, R140, or R172) - IDH mutational status will be assessed locally; for sites without local testing capabilities, a referral lab will be identified. b. By the investigator's assessment who are not candidates to receive intensive IC.
  • 5. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (Appendix D).
  • 6. Subject has adequate organ function defined as: - Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 3 x ULN, unless considered due to leukemic organ involvement. - Serum total bilirubin < 1.5 x ULN. Higher levels are acceptable if these can be attributed to ineffective erythropoiesis, ≤3 times the upper limit of normal for Gilbert's syndrome (eg, a gene mutation in UGT1A1), or leukemic organ involvement. - Serum creatinine < 2 x ULN or creatinine clearance > 30 mL/min based on the Modification of Diet in Renal Disease (MDRD) glomerular filtration rate (GFR): GFR (mL/min/1.73 m2) = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if African American)
  • 7. Agree to serial bone marrow aspirate/biopsies.
  • 8. Females of childbearing potential (FCBP)* may participate, providing they meet the following conditions: - Agree to practice true abstinence ** from sexual intercourse or to use highly effective contraceptive methods (eg, combined [containing estrogen and progestogen] or progestogen only associated with inhibition of ovulation, oral, injectable, intravaginal, patch, or implantable hormonal contraceptive; bilateral tubal occlusion; intrauterine device intrauterine hormone-releasing system; or male partner sterilization [note that a vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner of the FCBP trial participant and that a vasectomized partner has received medical assessment of the surgical success]) at screening and throughout the study, and for at least 4 months following the last study treatment; and - Have a negative serum β-subunit of human chorionic gonadotropin (βhCG) pregnancy test (sensitivity of at least 25 mIU/mL) at screening; and - Have a negative serum or urine (investigator's discretion under local regulations) β-hCG pregnancy test (sensitivity of at least 25 mIU/mL) within 72 hours prior to the start of study treatment in the Treatment Period (note that the screening serum pregnancy test can be used as the test prior to the start of study treatment in the Treatment Period if it is performed within the 72-hour timeframe).
  • 9. Male subjects must agree to practice true abstinence from sexual intercourse or agree to the use of highly effective contraceptive methods (as described above) with non-pregnant female partners of child bearing potential at screening and throughout the course of the study and should avoid conception with their partners during the course of the study and for at least 4 months following the last study treatment (6 months following last dose of azacitidine in Canada). Furthermore, the male subject must agree to use a condom while treated with azacitidine and for at least 4 months following the last azacitidine dose.
What rules you out
  • 1. Subject is suspected or proven to have acute promyelocytic leukemia based onmorphology, immunophenotype, molecular assay, or karyotype (Appendix B).
  • 10. Subject is known seropositive for or has active viral infection with human immunodeficiency virus (HIV), or active infection with hepatitis Bvirus (HBV) or hepatitis C virus (HCV)
  • 11. Subject is known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally
  • 12. Subject has uncontrolled hypertension (systolic blood pressure [BP] > 180 mmHg or diastolic BP > 100 mmHg)
  • 13. Subject is taking the following sensitive CYP substrate medications that have a narrow therapeutic range are excluded from the study unless the subject can be transferred to other medications at least 5 half-lives prior to the start of study treatment: phenytoin(CYP2C9), S-mephenytoin (CYP2C19), thioridazine (CYP2D6), theophylline, and tizanidine (CYP1A2) (Appendix K).
  • 14. Subject is taking the breast cancer resistance protein (BCRP) transporter-sensitive substrate rosuvastatin; subject should be excluded from the study unless he/she can be transferred to other medications at least 5 half-lives prior to the start of study treatment (Appendix L).
  • 15. Subject has active uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment).
  • 16. Subject has known or suspected hypersensitivity to any of the components of study therapy.
  • 17. Subject is taking medications that are known to prolong the QT interval (Appendix M) unless he/she can be transferred to other medications within ≥ 5 halflives prior to the start of study treatment. (If equivalent medication is not available, QTc will be closely monitored as defined in Section 8.1.)
  • 18. Subject has QTc interval (ie, Fridericia's correction [QTcF]) ≥ 450 ms or other factors that increase the risk of QT prolongation or arrhythmic events (eg, heart failure, hypokalemia, family history of long QT interval syndrome) at screening.
  • 19. Female subject who is pregnant or lactating.
  • 2. Subject has AML secondary to chronic myelogenous leukemia (CML; Appendix C).
  • 20. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
  • 21. Subject has any condition, including the presence of laboratory abnormalities, that places the subject at unacceptable risk if he/she were to participate in the study.
  • 22. Subject has any condition that confounds the ability to interpret data from the study.
  • 3. Subject has received a targeted agent against an IDH1 or IDH2 mutation.
  • 4. Subject has received prior systemic anticancer therapy, HSCT, or radiotherapy for AML. Note: Hydroxyurea is allowed prior to enrollment for the control of peripheral leukemic blasts in subjects with leukocytosis. (however, hydroxyurea should not be given within 72 hours prior to and after administration of azacitidine). For subjects with secondary AML (eg, MDS or MPN) treatment for prior cancer is not exclusionary; full treatment information will be collected within the CRF. The use of all trans retinoic acid (ATRA) for suspected APL is not exclusionary provided it is discontinued prior to initiation of treatment in the protocol.
  • 5. Subject has received more than 1 cycle of prior treatment with azacitidine, or subject has received any prior treatment with decitabine for MDS.
  • 6. Subject has or is suspected of having central nervous system (CNS) leukemia. Evaluation of cerebrospinal fluid is only required if CNS involvement by leukemia is suspected during screening.
  • 7. Subject has immediate life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.
  • 8. Subject has significant active cardiac disease within 6 months prior to the start of study treatment, including New York Heart Association (NYHA) class III or IV congestive heart failure (Appendix E); acute coronary syndrome (ACS); and/or stroke; or left ventricular ejection fraction (LVEF) < 40% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan obtained within 28 days prior to the start of study treatment.
  • 9. Subject has prior history of malignancy, other than MDS, MPN, or AML, unless the subject has been free of the disease for ≥ 1 year prior to the start of study treatment. However, subjects with the following history/concurrent conditions are allowed: -Basal or squamous cell carcinoma of the skin -Carcinoma in situ of the cervix -Carcinoma in situ of the breast -Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, node, metastasis clinical staging system)

The study team makes the final eligibility decision.

Where it's taking place

  • United Kingdom
  • Australia
  • United States
  • Canada
  • Switzerland
  • Korea, Republic of

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include United Kingdom; Australia; United States; Canada; Switzerland; Korea, Republic of. Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.