RECRUITING

APG-2575 in Combination With Novel Therapeutic Regimens in Subjects With Relapsed or Refractory Multiple Myeloma

Conditions

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a Phase Ib/II, open-label, multi-center study evaluating the safety, tolerability, efficacy, and PK/ Pharmacodynamics of APG-2575 in combination with Pd/DRd in patients with relapsed/refractory (RR) multiple myeloma (MM). The study consists of dose escalation and dose expansion phases. The study consists of will start with 2 arms noted below, both arms are independent

Official Title

A Phase Ib/II Open-Label Study of APG-2575 in Combination With Novel Therapeutic Regimens in Subjects With Relapsed or Refractory Multiple Myeloma and Immunoglobin Light Chain Amyloidosis

Quick Facts

Study Start:2021-12-23

Study Completion:2024-12-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04942067

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. ≥ 18 years of age 2. MM patients (for Arm A and Arm B): Patients with Relapsed/Refractory MM per 2016 IMWG criteria, previously treated with at least 1 but not more than 4 prior lines of therapy for MM. Refractory MM, meanwhile, is defined as disease that progresses on salvage therapy or progresses within 60 days of the last treatment. * Serum monoclonal protein ≥1.0 g/dl by protein electrophoresis * \>200 mg of monoclonal protein in the urine on 24-hour electrophoresis * Serum differential FLC concentration (dFLC, difference between amyloid forming \[involved\] and nonamyloid forming \[uninvolved\] free light chain \[FLC\]) \> 5 mg/dL; OR serum FLC of 7.5 mg/dL provided the κ/λ FLC ratio is abnormal (κ/λ \<0.26 for patients with monoclonal λ FLC, κ/λ \>1.65 for patients with monoclonal κ FLC). 3. Eastern Cooperative Oncology Group (ECOG) ≤ 2 4. Life expectancy ≥ 6 months 5. Adequate hematologic function defined as: 1. ANC ≥1.0 x 10\^9/L independent of growth factor support within 7 days of the first dose with study drug 2. Hemoglobin ≥8 g/dL without transfusion or growth factor support within 7 days of the first dose of study drug 3. Platelet count ≥ 50 x 10\^9/L without transfusion support within 7 days of the first dose of study drug (for MM patients); or platelet count ≥ 100 x 10\^9/L or ≥ 50 x 10\^9/L if bone marrow involvement independent of transfusion support in either (for AL amyloidosis patients). 6. Adequate hepatic and renal function defined as: 1. AST and ALT \< 3 x upper limit of normal (ULN) 2. Creatinine clearance \>30 mL/min (for MM patients); or Creatinine ≤3 mg/dL and CrCL ≥25 ml/min using the Cockcroft-Gault formula (for AL amyloidosis patients) 3. Bilirubin\< 1.5 x ULN (Except if considered secondary to Gilbert's syndrome and primarily indirect bilirubinemia) 7. PT/INR ≤2 x ULN and PTT (or aPTT) ≤2 x ULN 8. Female subjects who are of non-reproductive potential (i.e., post-menopausal by history: no menses for ≥2 year; or history of hysterectomy; or history of bilateral tubal ligation; or history of bilateral oophorectomy). Female subjects of childbearing potential must have a negative serum pregnancy test upon study entry. 9. Male and female subjects who agree to use highly effective methods of birth control (e.g., condoms, implants, injectables, combined oral contraceptives, some intrauterine devices\[IUDs\], sexual abstinence, or sterilized partner) during the period of therapy and for 90 days after the last dose of study drug 10. Ability to complete questionnaire(s) by themselves or with assistance (For AL amyloidosis patients only)	1. MM patients with newly diagnosed MM, previously untreated for MM or only had been treated with localized palliative treatment or steroids less than equivalent of dexamethasone 40 mg daily for 4 days). AL amyloidosis patients with AL amyloidosis have not been treated with any systemic therapy, or AL amyloidosis clinically overt multiple myeloma i.e. original CRAB criteria. Extent of marrow plasmacytosis is not prohibitive. 2. Subject has received antineoplastic therapy within 2 weeks before the date of initiating study treatment 3. Subject has previously received an allogenic stem cell transplant (regardless of timing) 4. Subjects planning to undergo a stem cell transplant prior to progression of disease on this study, i.e., these subjects should not be enrolled in order to reduce disease burden prior to transplant. 5. BCL-2-directed therapy within 4 weeks of initiating study treatment. (BCL-2 directed therapy more than 4 weeks before initiation of study treatment is allowed). 6. For Arm A/C only: The subjects show evidence of intolerance to pomalidomide, which is defined as subjects discontinued due to any AEs related to prior pomalidomide treatment 7. For Arm B only: The subjects show evidence of intolerance to daratumumab or lenalidomide, which is defined as subjects discontinued due to any AEs related to prior daratumumab or lenalidomide treatment 8. Patients with any uncontrolled active systemic infection, including but not limited to active hepatitis B or C virus infection, known human immunodeficiency virus (HIV) positive 9. Subject has peripheral neuropathy ≥grade 3 except caused by AL amyloidosis 10. Subject has plasma cell leukemia (\>2.0\*10\^9/L circulating plasma cells by standard differential) or Waldenström's macroglobulinemia or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 11. Plasmapheresis \<35 days prior to the initiation of study drug 12. Failure to have fully recovered (i.e., ≤ Grade 1 toxicity) from the reversible effects of prior treatment for MM or AL amyloidosis 13. 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 14. Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia (including Frederica corrected QT interval (QTc) ≥470 msec ) or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to initiating study treatment 15. Major surgical procedure within ≤14 days prior to initiating study treatment, or anticipation of the need for major surgery during the course of the study treatment, radiotherapy ≤14 days prior to initiating study treatment, systemic treatment within 14 days before the first dose of APG-2575 16. Recent infection requiring systemic treatment that was completed ≤14 days before the first dose of study drug 17. Vaccinated with live, attenuated vaccines within 4 weeks of initiation of APG-2575 (for patients' safety, patients could receive COVID-19 vaccination before or during study period as judged by HCP as beneficial) 18. Subject has any concurrent or recent malignancy ≤ 1 year prior to registration with the exception of: basal or squamous cell skin cancer, any carcinoma in situ. NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer. 19. Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor 20. Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia 21. History of stroke or intracranial hemorrhage within 6 months prior to enrollment 22. Any other condition or circumstance that would, in the opinion of the investigator, make the patient unsuitable for participation in the study

Inclusion Criteria

Exclusion Criteria

1. ≥ 18 years of age
2. MM patients (for Arm A and Arm B): Patients with Relapsed/Refractory MM per 2016 IMWG criteria, previously treated with at least 1 but not more than 4 prior lines of therapy for MM. Refractory MM, meanwhile, is defined as disease that progresses on salvage therapy or progresses within 60 days of the last treatment.
* Serum monoclonal protein ≥1.0 g/dl by protein electrophoresis
* \>200 mg of monoclonal protein in the urine on 24-hour electrophoresis
* Serum differential FLC concentration (dFLC, difference between amyloid forming \[involved\] and nonamyloid forming \[uninvolved\] free light chain \[FLC\]) \> 5 mg/dL; OR serum FLC of 7.5 mg/dL provided the κ/λ FLC ratio is abnormal (κ/λ \<0.26 for patients with monoclonal λ FLC, κ/λ \>1.65 for patients with monoclonal κ FLC).
3. Eastern Cooperative Oncology Group (ECOG) ≤ 2
4. Life expectancy ≥ 6 months
5. Adequate hematologic function defined as:
1. ANC ≥1.0 x 10\^9/L independent of growth factor support within 7 days of the first dose with study drug
2. Hemoglobin ≥8 g/dL without transfusion or growth factor support within 7 days of the first dose of study drug
3. Platelet count ≥ 50 x 10\^9/L without transfusion support within 7 days of the first dose of study drug (for MM patients); or platelet count ≥ 100 x 10\^9/L or ≥ 50 x 10\^9/L if bone marrow involvement independent of transfusion support in either (for AL amyloidosis patients).
6. Adequate hepatic and renal function defined as:
1. AST and ALT \< 3 x upper limit of normal (ULN)
2. Creatinine clearance \>30 mL/min (for MM patients); or Creatinine ≤3 mg/dL and CrCL ≥25 ml/min using the Cockcroft-Gault formula (for AL amyloidosis patients)
3. Bilirubin\< 1.5 x ULN (Except if considered secondary to Gilbert's syndrome and primarily indirect bilirubinemia)
7. PT/INR ≤2 x ULN and PTT (or aPTT) ≤2 x ULN
8. Female subjects who are of non-reproductive potential (i.e., post-menopausal by history: no menses for ≥2 year; or history of hysterectomy; or history of bilateral tubal ligation; or history of bilateral oophorectomy). Female subjects of childbearing potential must have a negative serum pregnancy test upon study entry.
9. Male and female subjects who agree to use highly effective methods of birth control (e.g., condoms, implants, injectables, combined oral contraceptives, some intrauterine devices\[IUDs\], sexual abstinence, or sterilized partner) during the period of therapy and for 90 days after the last dose of study drug
10. Ability to complete questionnaire(s) by themselves or with assistance (For AL amyloidosis patients only)

1. MM patients with newly diagnosed MM, previously untreated for MM or only had been treated with localized palliative treatment or steroids less than equivalent of dexamethasone 40 mg daily for 4 days). AL amyloidosis patients with AL amyloidosis have not been treated with any systemic therapy, or AL amyloidosis clinically overt multiple myeloma i.e. original CRAB criteria. Extent of marrow plasmacytosis is not prohibitive.
2. Subject has received antineoplastic therapy within 2 weeks before the date of initiating study treatment
3. Subject has previously received an allogenic stem cell transplant (regardless of timing)
4. Subjects planning to undergo a stem cell transplant prior to progression of disease on this study, i.e., these subjects should not be enrolled in order to reduce disease burden prior to transplant.
5. BCL-2-directed therapy within 4 weeks of initiating study treatment. (BCL-2 directed therapy more than 4 weeks before initiation of study treatment is allowed).
6. For Arm A/C only: The subjects show evidence of intolerance to pomalidomide, which is defined as subjects discontinued due to any AEs related to prior pomalidomide treatment
7. For Arm B only: The subjects show evidence of intolerance to daratumumab or lenalidomide, which is defined as subjects discontinued due to any AEs related to prior daratumumab or lenalidomide treatment
8. Patients with any uncontrolled active systemic infection, including but not limited to active hepatitis B or C virus infection, known human immunodeficiency virus (HIV) positive
9. Subject has peripheral neuropathy ≥grade 3 except caused by AL amyloidosis
10. Subject has plasma cell leukemia (\>2.0\*10\^9/L circulating plasma cells by standard differential) or Waldenström's macroglobulinemia or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
11. Plasmapheresis \<35 days prior to the initiation of study drug
12. Failure to have fully recovered (i.e., ≤ Grade 1 toxicity) from the reversible effects of prior treatment for MM or AL amyloidosis
13. 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
14. Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia (including Frederica corrected QT interval (QTc) ≥470 msec ) or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to initiating study treatment
15. Major surgical procedure within ≤14 days prior to initiating study treatment, or anticipation of the need for major surgery during the course of the study treatment, radiotherapy ≤14 days prior to initiating study treatment, systemic treatment within 14 days before the first dose of APG-2575
16. Recent infection requiring systemic treatment that was completed ≤14 days before the first dose of study drug
17. Vaccinated with live, attenuated vaccines within 4 weeks of initiation of APG-2575 (for patients' safety, patients could receive COVID-19 vaccination before or during study period as judged by HCP as beneficial)
18. Subject has any concurrent or recent malignancy ≤ 1 year prior to registration with the exception of: basal or squamous cell skin cancer, any carcinoma in situ. NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer.
19. Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor
20. Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
21. History of stroke or intracranial hemorrhage within 6 months prior to enrollment
22. Any other condition or circumstance that would, in the opinion of the investigator, make the patient unsuitable for participation in the study

Contacts and Locations

Study Contact

Angela Kaiser

CONTACT

301-509-0357

angela.kaiser@ascentage.com

Principal Investigator

Yifan Zhai, MD, PhD

STUDY_CHAIR

Ascentage Pharma Group Inc.

Study Locations (Sites)

Mayo Clinic

Jacksonville, Florida, 32224

United States

Weil Cornell Medical Center

New York, New York, 10065

United States

Cleveland Clinic Hosptials

Cleveland, Ohio, 44103

United States

Collaborators and Investigators

Sponsor: Ascentage Pharma Group Inc.

Yifan Zhai, MD, PhD, STUDY_CHAIR, Ascentage Pharma Group Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-12-23

Study Completion Date2024-12-01

Study Record Updates

Study Start Date2021-12-23

Study Completion Date2024-12-01

Terms related to this study

Additional Relevant MeSH Terms

Multiple Myeloma
Amyloidosis