A Phase Ib/II Study of APG-2575 in Combination With Azacitidine in Patients With Acute Myeloid Leukemia (AML), Mixed Phenotype Acute Leukemia (MPAL), Chronic Myelomonocytic Leukemia (CMML) and Higher-Risk Myelodysplastic Syndrome (MDS)
Study Identifier:
APG2575AU101
CT.gov Identifier:
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
N/A
Study Contact Information:
Will Be Recruiting
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Study Summary
To evaluate the safety, tolerability, efficacy and PK of APG-2575 in combination with Azacitidine in the patients with AML/MPAL or MDS/CMML.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Myelodysplastic Syndrome
Leukemia
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I/II
Sex
Female & Male
Age
18 - 99 Years
Study Drug
Drug: Arm: Experimental: APG2575 + Azacitidine 200 mg APG2575 dose ramp up +AZA Drug: APG 2575 ramp up arm APG2575 ramp up + Azacitidine ASCO 2025: In Part 1, LISA was administered at escalating doses (200, 400, 600, or 800 mg once daily [QD]) and combined with AZA to assess DLTs and determine the MTD. In Part 2 patients were treated with LISA 200, 400, or 600 mg QD over 28 or 14 days of 28-day cycles, combined with AZA at the standard dose (75 mg/m2 on days 1-7 or 1-5 and 8-9 of each cycle).
Study Status
Indicates the current recruitment status or the expanded access status
Will Be Recruiting
Requirements information
Inclusion criteria
- Patients with a diagnosis of histologically confirmed relapsed or refractory (R/R) acute myeloid leukemia (AML) or mixed phenotype acute leukemia (MPAL) or Chronic Myelomonocytic Leukemia (CMML) or relapsed/refractory Higher-Risk MDS by 2016 WHO classification for which no available standard therapies are indicated or anticipated to result in a durable response.
- MPAL will include biphenotypic leukemia, bilineal leukemia, undifferentiated leukemia, mixed lineage leukemia, leukemia of ambiguous lineage, T/myeloid leukemia, B/myeloid leukemia, or other diagnosis indicating the presence of multiple lineages within the cell population.
- Relapsed/refractory MDS will be defined as prior receipt of 4 cycles of HMA therapy with failure to attain a response, or progression of disease or relapse at any time after prior response to HMA therapy with Overall Revised International Prognostic Scoring System (IPSS-R) score > 3 (intermediate, high or very high).
Exclusion criteria
- Pregnant women.
- Uncontrolled intercurrent illness including, but not limited to active uncontrolled infection, symptomatic congestive heart failure (NYHA Class III or IV), unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Have had leukemia therapy within 14 days prior to starting investigational drug.
- However, patients with rapidly proliferative disease may receive hydroxyurea as needed until 24 hours prior to starting therapy on this protocol and during the first cycle of study.
- Have taken strong inhibitors or inducers of CYP3A4 within 7 days prior to the first dose of APG-2575.
- Have acute promyelocytic leukemia (French-American-British Class M3 AML or WHO classification APL with PML-RARA) or AML/MPAL with BCR-ABL1 positive.
- Active infection requiring systemic antibiotic/antifungal medication, known clinically active hepatitis B or C, or HIV infection or active COVID-19. (Patients who have received COVID-19 vaccination will be considered as eligible for the study.)
- Have active/ongoing graft-versus host disease (GVHD) or require continued treatment with systemic immunosuppressive agents (calcineurin inhibitors within 4 weeks prior to the first dose).
- Myeloablative therapy with autologous or allogeneic hematopoietic stem cell rescue within 6 months of study treatment initiation.
- Documented hypersensitivity to any of the components of the therapy program.
- Active, uncontrolled CNS leukemia.
- Men and women of childbearing potential who do not practice contraception. Women of childbearing potential and men must agree to use at least 1 form of barrier birth control (such as condom) prior to study entry and for the duration of study participation.
- History of other malignancies within 2 years prior to study entry, with the exception of:
- Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast.
- Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin.
- Previous malignancy confined and surgically resected (or treated with other modalities) with curative intention requires discussion with sponsor.
- Failure to have recovered (Grade > 1) from prior treatment (including chemotherapy, targeted therapy, immunotherapy, experimental agents, radiation, or surgery), except for alopecia.
- Unable to swallow tablets or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.
- Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, or corrected QT interval (QTc) ≥470 msec.
- Any other condition or circumstance that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Midwest
Grand Rapids, MI, United States, 49546
Investigator
Andrew Sochacki
Status
Will Be Recruiting
Condition(s) Treated at Site
Myelodysplastic Syndrome
Leukemia