Multiple MyelomaPhase 1/2NCT04942067
APG-2575 in Combination With Novel Therapeutic Regimens in Subjects With Relapsed or Refractory Multiple Myeloma
A Phase 1/2 study testing APG-2575+ Pd and APG-2575 + DRd in people with Multiple Myeloma and Amyloidosis, run by Ascentage Pharma Group Inc. at 3 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma, Amyloidosis
- What is being tested?
- APG-2575+ Pd and APG-2575 + DRd
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 108 participants
- Where
- 3 sitesUnited States
- Study dates
- 23 Dec 2021to 1 Dec 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥ 18 years of age
- 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.
- AL amyloidosis patients (for Arm C ONLY): Patients with AL amyloidosis when meeting:
- histochemical diagnosis based on detection by polarizing microscopy of green birefringent material in Congo red-stained tissue specimens, the type must have been confirmed unequivocally.
- have symptomatic organ involvement. Only purpura and/or carpal tunnel syndrome are not acceptable.
- have at least one prior line of systemic therapy for AL. Patients who do not achieve at least a PR to frontline therapy in 3 months are eligible.
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- All MM/AL patients should have measurable disease of AL amyloidosis as defined by at least ONE of the following:
- 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).
- Eastern Cooperative Oncology Group (ECOG) ≤ 2
- Life expectancy ≥ 6 months
- Adequate hematologic function defined as:
- ANC ≥1.0 x 10^9/L independent of growth factor support within 7 days of the first dose with study drug
- Hemoglobin ≥8 g/dL without transfusion or growth factor support within 7 days of the first dose of study drug
- 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).
- Adequate hepatic and renal function defined as:
- AST and ALT < 3 x upper limit of normal (ULN)
- 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)
- Bilirubin< 1.5 x ULN (Except if considered secondary to Gilbert's syndrome and primarily indirect bilirubinemia)
- PT/INR ≤2 x ULN and PTT (or aPTT) ≤2 x ULN
- 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.
- 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
- Ability to complete questionnaire(s) by themselves or with assistance (For AL amyloidosis patients only)
Who cannot join
- 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.
- Subject has received antineoplastic therapy within 2 weeks before the date of initiating study treatment
- Subject has previously received an allogenic stem cell transplant (regardless of timing)
- 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.
- 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).
- 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
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- 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
- 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
- Subject has peripheral neuropathy ≥grade 3 except caused by AL amyloidosis
- 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)
- Plasmapheresis <35 days prior to the initiation of study drug
- Failure to have fully recovered (i.e., ≤ Grade 1 toxicity) from the reversible effects of prior treatment for MM or AL amyloidosis
- 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
- 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
- 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
- Recent infection requiring systemic treatment that was completed ≤14 days before the first dose of study drug
- 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)
- 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.
- Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor
- Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment
- Any other condition or circumstance that would, in the opinion of the investigator, make the patient unsuitable for participation in the study
Trial locations and contacts
3 sites in 1 country.
United States3 sites, 3 recruiting
- Recruiting
Cleveland Clinic Hosptials
Cleveland, Ohio, 44103
- Recruiting
Mayo Clinic
Jacksonville, Florida, 32224
- Recruiting
Weil Cornell Medical Center
New York, New York, 10065
About this study
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
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
Read the detailed 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.
Arm A: APG-2575 will be administered in combination with Pd to determine the MTD and /RP2D of APG-2575 in subjects with R/R MM.
3+3 design will be utilized in dose escalation phase of APG-2575 in combination with Pd. The starting target dose of APG-2575 is 400 mg (dose level; DL1) and will be escalated in subsequent cohorts to 600 mg (DL2), 800 mg (DL3) accordingly. Dose reduction to 200 mg (DL-1) is acceptable if APG-2575 at dose of 400 mg cannot be tolerated. This rule-based design proceeds with cohorts of three patients. If none of the three patients enrolled in DL1 experiences a DLT, another three patients will be treated at DL2, and so on. However, if one patient experiences a DLT, three more patients will be treated at the same dose level. The dose escalation continues until at least two patients among a cohort of three to six patients experience DLT. MTD is conventionally defined as the highest dose level at which ≤ 33% of patients experience DLT. Higher dose level would be considered after a comprehensive analyses of safety data in the context of 800 mg can be well tolerated, otherwise, 800 mg (DL3) should be considered as MTD (Arm A). RP2D (Arm A) will be determined based on efficacy and safety profile of APG-2575 in combination with Pd.
Patients will receive APG-2575 at target dose once daily for 28 days plus pomalidomide (4 mg ) on Days 1 through 21 and dexamethasone (40 mg for patients ≤ 75 years old or 20 mg for patients > 75 years old) on Days 1, 8, 15, and 22 of a repeated 28-day cycle
- Conditions
- Multiple Myeloma, Amyloidosis
- Being tested
- APG-2575+ Pd, APG-2575 + DRd
- Medical subject headings
- Multiple Myeloma, Amyloidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APG-2575+ PdDrug
Also called APG-2575+ Pomalidomide + Dexamethasone
APG-2575 + Pomalidomide 4mg QD x 21 days + dexamethasone (40 mg for patients ≤ 75 years old or 20 mg for patients > 75 years old) on Days 1, 8, 15, and 22 of a repeated 28-day cycle
APG-2575 + DRdDrug
Also called APG-2575+ Lenalidomide +Dexamethasone+Daratumumab
APG-2575+ Lenalidomide administered at a dose of 25 mg orally (PO) on Days 1 through 21 of each 28-day cycle, dexamethasone will be administered at a dose of 40 mg (or 20 mg for patients > 75 years old) once weekly, and daratumumab will be administered intravenously at a dose of 16 mg/kg (or 1800 mg administered subcutaneously if commercially available) weekly in cycles 1 and 2 and then every 2 weeks in cycles 3 to 6 and every 4 weeks thereafter.
| Study group | Role | What they receive |
|---|---|---|
| APG-2575 +Pd or LD | Experimental | APG-2575+ Pomalidomide 4mg QD x 21 days + dexamethasone Receives: Drug: APG-2575+ Pd |
| APG-2575+LD | Experimental | APG-2575+ Lenalidomide +Dexa Days 1 through 21 of each 28-day cycle, Receives: Drug: APG-2575 + DRd |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicity
DLT will be defined based on the rate of drug-related grade 3-5 adverse events experienced within the first 6 weeks (2 cycles) of study treatment. These will be assessed via CTCAE version 5.0
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2021
- Study start23 Dec 2021
- Primary completion1 Sep 2024 (estimated)
- Study completion1 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Ascentage Pharma Group Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- dose escalation and dose expansion after MTD
- Masking
- None (open label)
- Enrolment
- 108 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ascentage Pharma Group Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yifan Zhai, MD, PhD, Study chair, Ascentage Pharma Group Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04942067
- Sponsor's protocol ID
- APG2575MU101
- Status last verified
- Oct 2023
- First submitted
- 29 Jul 2020
- Last updated
- 25 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04942067
- Acronym / sponsor ID
- APG2575MU101
- Conditions
- Multiple Myeloma, Amyloidosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 108 participants (estimated)
- Lead sponsor
- Ascentage Pharma Group Inc.Industry (pharma, biotech, devices)
- Study start
- 23 Dec 2021 (actual)
- Primary completion
- 1 Sep 2024 (estimated)
- Study completion
- 1 Dec 2024 (estimated)
- First posted
- 28 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed 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.
Arm A: APG-2575 will be administered in combination with Pd to determine the MTD and /RP2D of APG-2575 in subjects with R/R MM.
3+3 design will be utilized in dose escalation phase of APG-2575 in combination with Pd. The starting target dose of APG-2575 is 400 mg (dose level; DL1) and will be escalated in subsequent cohorts to 600 mg (DL2), 800 mg (DL3) accordingly. Dose reduction to 200 mg (DL-1) is acceptable if APG-2575 at dose of 400 mg cannot be tolerated. This rule-based design proceeds with cohorts of three patients. If none of the three patients enrolled in DL1 experiences a DLT, another three patients will be treated at DL2, and so on. However, if one patient experiences a DLT, three more patients will be treated at the same dose level. The dose escalation continues until at least two patients among a cohort of three to six patients experience DLT. MTD is conventionally defined as the highest dose level at which ≤ 33% of patients experience DLT. Higher dose level would be considered after a comprehensive analyses of safety data in the context of 800 mg can be well tolerated, otherwise, 800 mg (DL3) should be considered as MTD (Arm A). RP2D (Arm A) will be determined based on efficacy and safety profile of APG-2575 in combination with Pd.
Patients will receive APG-2575 at target dose once daily for 28 days plus pomalidomide (4 mg ) on Days 1 through 21 and dexamethasone (40 mg for patients ≤ 75 years old or 20 mg for patients > 75 years old) on Days 1, 8, 15, and 22 of a repeated 28-day cycle
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- dose escalation and dose expansion after MTD
| Arm | Type | Receives |
|---|---|---|
| APG-2575 +Pd or LD | Experimental | Drug: APG-2575+ PdAPG-2575+ Pomalidomide 4mg QD x 21 days + dexamethasone |
| APG-2575+LD | Experimental | Drug: APG-2575 + DRdAPG-2575+ Lenalidomide +Dexa Days 1 through 21 of each 28-day cycle, |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- ≥ 18 years of age
- 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.
- Eastern Cooperative Oncology Group (ECOG) ≤ 2
- Life expectancy ≥ 6 months
- Adequate hematologic function defined as:
Key exclusion criteria (22 listed)
- 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.
- Subject has received antineoplastic therapy within 2 weeks before the date of initiating study treatment
- Subject has previously received an allogenic stem cell transplant (regardless of timing)
- 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.
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| APG-2575+ PdAlso: APG-2575+ Pomalidomide + DexamethasoneAPG-2575 + Pomalidomide 4mg QD x 21 days + dexamethasone (40 mg for patients ≤ 75 years old or 20 mg for patients > 75 years old) on Days 1, 8, 15, and 22 of a repeated 28-day cycle | Drug | APG-2575 +Pd or LD |
| APG-2575 + DRdAlso: APG-2575+ Lenalidomide +Dexamethasone+DaratumumabAPG-2575+ Lenalidomide administered at a dose of 25 mg orally (PO) on Days 1 through 21 of each 28-day cycle, dexamethasone will be administered at a dose of 40 mg (or 20 mg for patients > 75 years old) once weekly, and daratumumab will be administered intravenously at a dose of 16 mg/kg (or 1800 mg administered subcutaneously if commercially available) weekly in cycles 1 and 2 and then every 2 weeks in cycles 3 to 6 and every 4 weeks thereafter. | Drug | APG-2575+LD |
Primary outcome
Dose limiting toxicity
Time frame: 28 days
DLT will be defined based on the rate of drug-related grade 3-5 adverse events experienced within the first 6 weeks (2 cycles) of study treatment. These will be assessed via CTCAE version 5.0
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yifan Zhai, MD, PhD study chair
Ascentage Pharma Group Inc.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing APG-2575+ Pd and APG-2575 + DRd in people with Multiple Myeloma and Amyloidosis, run by Ascentage Pharma Group Inc. at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Angela Kaiser (301-509-0357, angela.kaiser@ascentage.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose limiting toxicity (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2023.