ZIFTOMENIB for Relapsed or refractory acute myeloid leukemia

Inclusion criteria

• {"criterion_text":"- 1. Relapsed/refractory (R/R) acute myeloid leukemia (AML) defined as those who have also failed or are not appropriate for any approved standard-of-care (SOC) therapies or hematopoietic stem cell transplant (HSCT)with reappearance of ≥ 5% blasts in the bone marrow (BM)\n- 2. ≥ 18 years of age\n- 3. Eastern Cooperative Oncology Group performance status of ≤ 2, and a life expectancy of at least 2 months\n- 4. Peripheral white blood cell counts ≤ 30,000/μL"}

Exclusion criteria

• {"criterion_text":"- 1. Diagnosis of acute promyelocytic leukemia or chronic myelogenous leukemia in blast crisis\n- 2. Donor lymphocyte infusion < 30 days prior to study entry\n- 3. Clinically active central nervous system (CNS) leukemia\n- 4. Has undergone HSCT and has not had adequate hematologic recovery (Recovery is defined as peripheral absolute neutrophil count (ANC) ≥ 1 × 10^9/L and platelets at least ≥ 50 × 10^9/L [but preferably ≥ 100 × 10^9/L] and signs of a cellular BM at any time after HSCT).\n- 5. Patients on immunosuppressive therapy post HSCT must be off all immunosuppression therapy within 2 weeks of Cycle 1 Day 1\n- 6. ≥ Grade 2 active acute GvHD, moderate or severe limited chronic GvHD, or extensive chronic GvHD of any severity\n- 7. Has received prior menin inhibitor\n- 8. Has received chemotherapy, immunotherapy, radiotherapy (unless if given for management of CNS leukemia), or any ancillary therapy that is considered to be investigational (ie, used for non-approved indications(s) and in the context of a research investigation) < 14 days prior to the first dose of ziftomenib or within 5 drug half-lives prior to the first dose of study drug, whichever is shorter, to ensure that patient time without necessary AML therapy is appropriately limited\n- 9. Requires treatment with concomitant drugs that are strong inducers of CYP3A4 with the exception of antibiotics, antifungals, and antivirals that are used as SOC or to prevent or treat infections. Other such drugs that are considered absolutely essential by the Investigator for the care of the patient should be discussed on a case-by-case basis with the Medical Monitor\n- 10. Has an active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection\n- 11. Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension or arrhythmia, history of cerebrovascular accident including transient ischemic attack within the past 6 months, congestive heart failure (New York Heart Association Class III or IV) related to primary cardiac disease, ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to the first dose of study treatment\n- 12. Mean corrected QT interval by Fredericia's formula > 480 ms on triplicate electrocardiograms"}

Primary endpoints

• {"endpoint_text":"- Phase 1 Part 1a: 1. Maximum Tolerated Dose (MTD)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase 1 Part 1a: 2. Recommended Phase 2 dose (RP2D)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase 1 Part 1b: 1. Safety, tolerability, and efficacy at multiple timepoints during the study","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase 2: 1. Based on evaluation of CR/CRh","definition_or_measurement_approach":"Evaluation of clinical remission outcomes (CR/CRh) per study-specified response criteria"}
• {"endpoint_text":"- Sub-study 3: Safety, tolerability, and efficacy at multiple timepoints during the study","definition_or_measurement_approach":""}
• {"endpoint_text":"- Sub study 4: Based on evaluation of CR/CRh","definition_or_measurement_approach":"Evaluation of clinical remission outcomes (CR/CRh) per study-specified response criteria"}
• {"endpoint_text":"- Sub study 2: PK parameters of ziftomenib and ziftomenib metabolites: AUC0-∞, AUC0-t, Cmax, Tmax, t1/2, CL/F, and Vz/F","definition_or_measurement_approach":"Plasma pharmacokinetic measurements: AUC0-∞, AUC0-t, Cmax, Tmax, t1/2, CL/F, Vz/F"}

Secondary endpoints

• {"endpoint_text":"- Phase 1 Part 1a: 1. Safety/tolerability assessed at multiple timepoints during the study","definition_or_measurement_approach":"Assessment of adverse events and tolerability (e.g., NCI CTCAE v5.0) at prespecified timepoints"}
• {"endpoint_text":"- Phase 1 Part 1a: 2. From blood samples collected at specified timepoints during treatment","definition_or_measurement_approach":"Laboratory and PK/biomarker analyses from blood samples collected at specified timepoints"}
• {"endpoint_text":"- Phase 1 Part 1a: 3. Plasma concentrations of ziftomenib and metabolite(s)","definition_or_measurement_approach":"Measurement of plasma drug and metabolite concentrations"}
• {"endpoint_text":"- Phase 1 Part 1a: 4. Plasma PK parameters (Cmax, Cmin, Tmax, AUC0-t, AUC0-8, CL/F, Vz/F, and t½)","definition_or_measurement_approach":"Calculation of standard PK parameters from plasma concentration-time data"}
• {"endpoint_text":"- Phase 1 Part 1a: 5. Based on evaluation of (including but not limited to): a. Duration of CR/CRh, b. TI, c. CR/CRh MRD negativity, d. CRc (CR+ CRh + CRi), e. ORR (CR + CRh + CRi + MLFS), f. EFS, g. OS","definition_or_measurement_approach":"Clinical response and survival endpoints evaluated per protocol definitions (CR/CRh, TI, MRD status, CRc, ORR, EFS, OS)"}
• {"endpoint_text":"- Phase 1 Part 1b: 1. Based on evaluation of (including but not limited to): a. Duration of CR/CRh, b. TI, c. CR/CRh MRD negativity, d. CRc, e. EFS, f. OS","definition_or_measurement_approach":"Clinical response and survival endpoints evaluated per protocol definitions"}
• {"endpoint_text":"- Phase 2: 1. Based on evaluation of (including but not limited to): a. Duration of CR/CRh, b. TI, c. CR/CRh MRD negativity, d. CRc e. EFS, f. OS","definition_or_measurement_approach":"Clinical response and survival endpoints evaluated per protocol definitions"}
• {"endpoint_text":"- Phase 2: 2. Safety and tolerability assessed at multiple timepoints during the study","definition_or_measurement_approach":"Assessment of adverse events and tolerability over study visits"}
• {"endpoint_text":"- Sub-study 3: Based on evaluation of (including but not limited to): a. Rate of CR, b. Duration of CR, c. CR MRD negativity, d. Rate of CR/CRh/CRi, e. Duration of CR/CRh/CRi, f. CR/CRh/CRi MRD negativity, g. EFS, h. OS","definition_or_measurement_approach":"Response rates, MRD status and survival endpoints per protocol definitions"}
• {"endpoint_text":"- Sub-study 4: Based on evaluation of (including but not limited to): a. Duration of CR/CRh b. TI c. CR/CRh, CRc, and ORR MRD negativity d. CRc e. ORR f. EFS g.OS","definition_or_measurement_approach":"Response, MRD and survival endpoints per protocol definitions"}
• {"endpoint_text":"- Sub-study 4: Safety, tolerability, and efficacy assessed at multiple timepoints during the study: a. Incidence and severity of AEs according to NCI CTCAE v5.0 b. Incidence of SAEs c. Deaths on treatment d.\tDiscontinuations of study treatment due to AEs e.\tClinically significant changes in clinical laboratory parameters, vital signs parameters, ECG parameters f. Change in ECOG status","definition_or_measurement_approach":"Safety monitoring including NCI CTCAE v5.0 AE reporting, laboratory, vitals, ECGs, and ECOG assessments"}
• {"endpoint_text":"- Sub study 4: Plasma PK parameters (Cmax, Cmin, Tmax, AUC0-t, AUC0∞, CL/F, Vz/F, and t1/2)","definition_or_measurement_approach":"Calculation of PK parameters from plasma concentration-time profiles"}
• {"endpoint_text":"- Sub study 2: QT interval corrected for heart rate using Fridericia’s formula and time-matched ziftomenib plasma concentration measurements","definition_or_measurement_approach":"Time-matched ECG QTcF measurements correlated with plasma drug concentrations"}

Spain

Earliest CTIS Part Ii Submission Date

20-06-2024

Latest Decision Or Authorization Date

08-07-2024

Processing Time Days

18

Number Of Sites

7

Number Of Participants

30

France

Earliest CTIS Part Ii Submission Date

08-07-2024

Latest Decision Or Authorization Date

17-07-2024

Processing Time Days

9

Number Of Sites

6

Number Of Participants

35

Belgium

Earliest CTIS Part Ii Submission Date

20-06-2024

Latest Decision Or Authorization Date

11-07-2024

Processing Time Days

21

Number Of Sites

2

Number Of Participants

15

Italy

Earliest CTIS Part Ii Submission Date

20-06-2024

Latest Decision Or Authorization Date

15-07-2024

Processing Time Days

25

Number Of Sites

4

Number Of Participants

25

Germany

Earliest CTIS Part Ii Submission Date

20-06-2024

Latest Decision Or Authorization Date

09-07-2024

Processing Time Days

19

Number Of Sites

2

Number Of Participants

25

Poland

Earliest CTIS Part Ii Submission Date

20-06-2024

Latest Decision Or Authorization Date

15-07-2024

Processing Time Days

25

Number Of Sites

1

Number Of Participants

15

Primary sponsor

Full Name

Kura Oncology Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Syneos Health Germany GmbH

Responsibilities

sponsorDuties codes: [8]; contact email: brigitte.heckner@syneoshealth.com

Name

Iqvia Biotech Limited

Responsibilities

sponsorDuties codes: [1,10,12,2,5,6,7]; contact email: Biotech-EUCTR-Support@iqvia.com

Name

Eresearchtechnology Inc.

Responsibilities

sponsorDuties codes: [4]; contact email: Mackenzie.perkett@clario.com

Third parties

• {"country":"United States","full_name":"Frontage Laboratories Inc.","duties_or_roles":"sponsorDuties codes: [4]; contact email: bwalter@frontagelab.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"sponsorDuties codes: [4]; contact email: Holli.Sagely@azenta.com","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Syneos Health Germany GmbH","duties_or_roles":"sponsorDuties codes: [8]; contact email: brigitte.heckner@syneoshealth.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"sponsorDuties: [15] value: \"IVRS30 – treatment randomisation\"; contact email: emclellan@suvoda.com","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Iqvia Biotech Limited","duties_or_roles":"sponsorDuties codes: [1,10,12,2,5,6,7]; contact email: Biotech-EUCTR-Support@iqvia.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Neogenomics Laboratories Inc.","duties_or_roles":"sponsorDuties codes: [4]; contact email: HoustonPharmaTeam@neogenomics.com","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Invivoscribe Inc.","duties_or_roles":"sponsorDuties codes: [4]; contact email: misaac@labpmm.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"sponsorDuties codes: [4]; contact email: EA-operations@expressionanalysis.com","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"sponsorDuties: [15] value: \"Sample processing\"; contact email: stuart.moran@q2labsolutions.com","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"sponsorDuties codes: [4]; contact email: Mackenzie.perkett@clario.com","organisation_type":"Pharmaceutical company"}