Waldenstrom MacroglobulinemiaPhase 1MAPLE-1NCT04260217
APG-2575 Single Agent or in Combination With Ibrutinib or Rituximab in Patients With Waldenström Macroglobulinemia
A Phase 1 study testing APG2575 400 mg, APG2575 600 mg and APG2575 800 mg in people with Waldenstrom Macroglobulinemia, run by Ascentage Pharma Group Inc. at 14 sites in 3 countries.
Trial summary
Phase Ib/II study of safety, tolerability, efficacy and PK of APG-2575 as a single agent or in combination with other therapeutic agents including ibrutinib or rituximab. Read more about this study
- Who is it for?
- Ages 18 to 95 years
- Conditions the study is for
- Waldenstrom Macroglobulinemia
- What is being tested?
- APG2575 400 mg, APG2575 600 mg and APG2575 800 mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 14 sitesin 3 countries
- Study dates
- 30 May 2021to 13 Aug 2025
- Phase
- Phase 1
- 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 to 95 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Criteria for inclusion:
- Patients must meet all of the following inclusion criteria to be eligible for participation in this study:
- Local confirmed clinicopathological diagnosis of WM in accordance with the consensus panel of the Second International Workshop on WM (Owen 2003).
- WM patients with symptomatic and measurable disease (defined as presence of serum immunoglobulin M (IgM)>0.5g/dL), requiring treatment as per mSMART guidelines (Kyle 2003): with B symptoms (fever, night sweats, fatigue, night sweats weight loss), progressive lymphadenopathy or splenomegaly, anemia (hemoglobin value of <10 g/dL) or platelet count <100*109/L due to marrow infiltration. Complications such as hyperviscosity syndrome, symptomatic sensorimotor peripheral neuropathy due to WM, systemic amyloidosis related to WM, renal insufficiency related to WM, or symptomatic cryoglobulinemia may also be indications for therapy.
- For Arm A only: Have received at least one prior therapy for WM. Patient must have either failed (defined as progressing while on or within 6 months of treatment with ibrutinib treatment) or intolerant to ibrutinib.
- For Arm B only: Previously untreated WM.
Show all 40Show fewer
- For Arm C only: Have received at least one prior therapy, relapsed or refractory WM.
- Adequate hematologic function defined as:
- ANC ≥1.0 x 109/L independent of growth factor support within 7 days of the first dose with study drug.
- Hemoglobin ≥9 g/dL without transfusion or growth factor support within 7 days of the first dose of study drug.
- Platelet count ≥ 75 x 109/L without transfusion support within 7 days of the first dose of study drug.
- Adequate hepatic and renal function defined as:
- AST and ALT < 2.5 x ULN (upper limit of normal)
- Glomerular filtration rate (GFR) >30mL/min
- Bilirubin< 1.5 x ULN
- PT/INR ≤1.5 x ULN and PTT (aPTT) ≤1.5 x ULN.
- ≥18 years of age.
- Eastern Cooperative Oncology Group (ECOG) ≤1.
- Life expectancy≥3 months.
- 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 30 days after the last dose of study drug and 90 days (males) after the last dose of study drug.
- Symptomatic disease meeting at least 1 of the recommendations from the Second International Workshop on Waldenström Macroglobulinemia for requiring treatment (Kyle 2003):
- Constitutional symptoms documented in the subject's chart with supportive objective measures, as appropriate, defined as one or more of the following disease-related symptoms or signs:
- Unintentional weight loss ≥10% within the previous 6 months prior to Screening
- Fevers higher than 100.5°F or 38.0°C for 2 or more weeks prior to Screening without evidence of infection
- Night sweats for more than 1 month prior to Screening without evidence of infection
- Clinically relevant fatigue which is not relieved by rest due to WM
- Symptomatic hyperviscosity or serum viscosity levels greater than 4.0 centipoises
- Lymphadenopathy which is either symptomatic or bulky (≥5cm in maximum diameter)
- Symptomatic hepatomegaly and/or splenomegaly and/or organ tissue infiltration
- Peripheral neuropathy due to WM
- Symptomatic cryoglobulinemia
- Cold agglutinin anemia
- IgM related immune hemolytic anemia and/or thrombocytopenia
- Nephropathy related to WM
- Amyloidosis related to WM
- Hemoglobin ≤10g/dL
- Platelet count <100 x109/L
- Serum monoclonal protein >5g/dL, with or without overt clinical symptoms.
- Any other condition or circumstance that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.
Who cannot join
- Criteria for exclusion:
- Patients who meet any of the following exclusion criteria are not to be enrolled in this study:
- For Arm A only: Patients who have never been treated with ibrutinib.
- For Arm B only: Patients who have previously received any treatment for WM.
- For Arm C only:
- Patients who have previously been treated with ibrutinib or other BTK inhibitor.
Show all 24Show fewer
- Disease that is refractory to the last prior rituximab based-therapy defined as either Relapse after the last rituximab-based therapy (<12 months since last dose of rituximab), OR Failure to achieve at least a MR after the last rituximab-based therapy.
- Rituximab treatment within the last 12 months before the first dose of study drug.
- Known anaphylaxis or IgE-mediated hypersensitivity to murine proteins or to any component of rituximab.
- Patients with central nervous system involvement (Bing-Neel syndrome), active infection (including active hepatitis B or C virus infection, known human immunodeficiency virus (HIV) positive) or any other serious (unresolved) medical condition.
- Plasmapheresis <35 days prior to the initiation of study drug. (Note: Subjects with high IgM values or hyper-viscosity symptoms during screening may receive plasmapheresis prior to initiating study drug if the previous plasmapheresis was performed >35 days before the plasmapheresis performed during screening (in order to obtain a true baseline IgM value for efficacy evaluations).
- Failure to have fully recovered (i.e., ≤Grade 1 toxicity) from the reversible effects of prior treatment for WM.
- 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.
- 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.
- History of active or chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) defined by positive polymerase chain reaction (PCR).
- Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia 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 randomization.
- 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.
- Any uncontrolled active systemic infection.
- Any concurrent malignancy.
- Concomitant use of warfarin or other Vitamin K antagonists (eg. phenoprocoumon).
- Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor.
- Known bleeding disorders (eg, von Willebrand's disease) or hemophilia.
- History of stroke or intracranial hemorrhage within 12 months prior to enrollment.
Trial locations and contacts
14 sites in 3 countries.
14 sites in 3 countries
China8 sites
Beijing Chaoyang Hospital
Beijing
Nanfang Hospital
Guangzhou, Guangdong
The First Affiliated Hospital,College Of Medicine,Zhejiang University
Hangzhou
The First Affiliated Hospital with Nanjing Medical University
Nanjing
Zhongshan Hospital of Fudan University
Shanghai, Shanghai Municipality
The First Affiliated Hospital Of Soochow University
Suzhou
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences
Tianjin
Henan Cancer Hospital
Zhengzhou
United States5 sites
Colorado Blood Cancer Institute
Denver, Colorado, 80218
City of Hope
Duarte, California, 91010
MD Anderson
Houston, Texas, 77030
Mayo Clinic
Jacksonville, Florida, 32224
Weill Cornell Univ Hospitals
New York, New York, 10065
About this study
Official title: A Phase Ib /II Open-label, Multi-center Study to Evaluate the Safety, Tolerability and Efficacy of APG-2575 Single Agent or in Combination With Ibrutinib or Rituximab in Patients With Waldenström Macroglobulinemia (MAPLE-1)
Phase Ib/II study of safety, tolerability, efficacy and PK of APG-2575 as a single agent or in combination with other therapeutic agents including ibrutinib or rituximab.
Read the detailed description
This is an open-label, multi-center Phase Ib/II study of safety, tolerability, efficacy and PK of APG-2575 as a single agent or in combination with other therapeutic agents including ibrutinib or rituximab. The study consists of the dose escalation and the dose expansion phases. The clinical trial will have multiple arms with ability to subsequently add more treatment arms based upon clinical activity of APG2575 in WM. Initially the study will contain 3 arms noted below, all the arms are independent.
Arm A: APG-2575 will be administered as a single agent to determine the MTD/RP2D in subjects who are relapsed/resistant or intolerant to ibrutinib or other BTK inhibitors.
The Dose escalation phase of APG-2575 as monotherapy will use mTPI-2 design. The starting target dose (using ramp-up if needed) is 400 mg (dose level; DL1) and will be increased to 600 mg (DL2), 800 mg (DL3) accordingly. Doses can be increased to higher level depending on safety and PK results based on discussions of the Investigators and Sponsor. APG-2575 will be administered orally once daily until time of progression or unacceptable toxicity. After the MTD/RP2D is determined, up to 12 additional patients will be enrolled at RP2D in dose-expansion phase to further evaluate safety and efficacy of APG-2575.
Arm B: APG-2575 will be administered in combination with ibrutinib in subjects with previously untreated WM.
- Conditions
- Waldenstrom Macroglobulinemia
- Being tested
- APG2575 400 mg, APG2575 600 mg, APG2575 800 mg
- Medical subject headings
- Waldenstrom Macroglobulinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APG2575 400 mgDrug
APG2575 400 mg
APG2575 600 mgDrug
APG2575 600 mg
APG2575 800 mgDrug
APG2575 800 mg
| Study group | Role | What they receive |
|---|---|---|
| APG2575 400 mg | Experimental | APG2575 400mg ramp up arm Receives: Drug: APG2575 400 mg; Drug: APG2575 600 mg; Drug: APG2575 800 mg |
| APG2575 600 mg | Experimental | APG2575 600 mg ramp up arm Receives: Drug: APG2575 600 mg; Drug: APG2575 800 mg |
| APG2575 800 mg arm | Experimental | APG2575 800 mg arm ramp up Receives: Drug: APG2575 800 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Toxicity Endpoint: dose limiting toxicity (DLT)
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: 42 days
Maximally tolerated dose (MTD)
MTD will be determined based on DLTs observed during the first 6 weeks (2 cycles) of study treatment
Measured: 42 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2020
- Study start30 May 2021
- Primary completion5 Feb 2024
- Study completion13 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Waldenstrom MacroglobulinemiaStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- APG2575 400 mg ramp up arm
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ascentage Pharma Group Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04260217
- Sponsor's protocol ID
- APG2575WU101
- Acronym
- MAPLE-1
- Status last verified
- Aug 2025
- First submitted
- 5 Feb 2020
- Last updated
- 19 Aug 2025
- 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 19 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib /II Open-label, Multi-center Study to Evaluate the Safety, Tolerability and Efficacy of APG-2575 Single Agent or in Combination With Ibrutinib or Rituximab in Patients With Waldenström Macroglobulinemia (MAPLE-1)
- ClinicalTrials.gov ID
- NCT04260217
- Acronym / sponsor ID
- MAPLE-1 / APG2575WU101
- Conditions
- Waldenstrom Macroglobulinemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Ascentage Pharma Group Inc.Industry (pharma, biotech, devices)
- Study start
- 30 May 2021 (actual)
- Primary completion
- 5 Feb 2024 (actual)
- Study completion
- 13 Aug 2025 (actual)
- First posted
- 7 Feb 2020 (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.
Phase Ib/II study of safety, tolerability, efficacy and PK of APG-2575 as a single agent or in combination with other therapeutic agents including ibrutinib or rituximab.
Detailed description
This is an open-label, multi-center Phase Ib/II study of safety, tolerability, efficacy and PK of APG-2575 as a single agent or in combination with other therapeutic agents including ibrutinib or rituximab. The study consists of the dose escalation and the dose expansion phases. The clinical trial will have multiple arms with ability to subsequently add more treatment arms based upon clinical activity of APG2575 in WM. Initially the study will contain 3 arms noted below, all the arms are independent.
Arm A: APG-2575 will be administered as a single agent to determine the MTD/RP2D in subjects who are relapsed/resistant or intolerant to ibrutinib or other BTK inhibitors.
The Dose escalation phase of APG-2575 as monotherapy will use mTPI-2 design. The starting target dose (using ramp-up if needed) is 400 mg (dose level; DL1) and will be increased to 600 mg (DL2), 800 mg (DL3) accordingly. Doses can be increased to higher level depending on safety and PK results based on discussions of the Investigators and Sponsor. APG-2575 will be administered orally once daily until time of progression or unacceptable toxicity. After the MTD/RP2D is determined, up to 12 additional patients will be enrolled at RP2D in dose-expansion phase to further evaluate safety and efficacy of APG-2575.
Arm B: APG-2575 will be administered in combination with ibrutinib in subjects with previously untreated WM.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- APG2575 400 mg ramp up arm
| Arm | Type | Receives |
|---|---|---|
| APG2575 400 mg | Experimental | Drug: APG2575 400 mg, Drug: APG2575 600 mg, Drug: APG2575 800 mgAPG2575 400mg ramp up arm |
| APG2575 600 mg | Experimental | Drug: APG2575 600 mg, Drug: APG2575 800 mgAPG2575 600 mg ramp up arm |
| APG2575 800 mg arm | Experimental | Drug: APG2575 800 mgAPG2575 800 mg arm ramp up |
Who may qualify
- Ages
- 18 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (40 listed)
- Criteria for inclusion:
- Patients must meet all of the following inclusion criteria to be eligible for participation in this study:
- Local confirmed clinicopathological diagnosis of WM in accordance with the consensus panel of the Second International Workshop on WM (Owen 2003).
- WM patients with symptomatic and measurable disease (defined as presence of serum immunoglobulin M (IgM)>0.5g/dL), requiring treatment as per mSMART guidelines (Kyle 2003): with B symptoms (fever, night sweats, fatigue, night sweats weight loss), progressive lymphadenopathy or splenomegaly, anemia (hemoglobin value of <10 g/dL) or platelet count <100*109/L due to marrow infiltration. Complications such as hyperviscosity syndrome, symptomatic sensorimotor peripheral neuropathy due to WM, systemic amyloidosis related to WM, renal insufficiency related to WM, or symptomatic cryoglobulinemia may also be indications for therapy.
- For Arm A only: Have received at least one prior therapy for WM. Patient must have either failed (defined as progressing while on or within 6 months of treatment with ibrutinib treatment) or intolerant to ibrutinib.
Key exclusion criteria (24 listed)
- Criteria for exclusion:
- Patients who meet any of the following exclusion criteria are not to be enrolled in this study:
- For Arm A only: Patients who have never been treated with ibrutinib.
- For Arm B only: Patients who have previously received any treatment for WM.
- For Arm C only:
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 |
|---|---|---|
| APG2575 400 mgAPG2575 400 mg | Drug | APG2575 400 mg |
| APG2575 600 mgAPG2575 600 mg | Drug | APG2575 400 mg, APG2575 600 mg |
| APG2575 800 mgAPG2575 800 mg | Drug | APG2575 400 mg, APG2575 600 mg, APG2575 800 mg arm |
Primary outcome
Primary Toxicity Endpoint: dose limiting toxicity (DLT)
Time frame: 42 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
Maximally tolerated dose (MTD)
Time frame: 42 days
MTD will be determined based on DLTs observed during the first 6 weeks (2 cycles) of study treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2025.
Related trials for Waldenstrom Macroglobulinemia
RecruitingPhase 2
Testing the Combination of Venetoclax and Rituximab, in Comparison to the Usual Treatment (Ibrutinib Plus Rituximab or Zanubrutinib Alone) for Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma
Lymphoplasmacytic Lymphoma, Waldenstrom Macroglobulinemia
Not yet recruitingPhase 2
Epcoritamab as Consolidative Therapy for Waldenstr(SqrRoot)(Delta)m Macroglobulinemia (WM) Treated With a Bruton Tyrosine Kinase Inhibitor (BTKi)
Waldenstrom Macroglobulinemia
Active, not recruitingObservational study
Clinical, Laboratory and Epidemiologic Characterization of Individuals and Families at High Risk of Hematologic Cancer
Waldenstrom Macroglobulinemia, Chronic Lymphocytic Leukemia
RecruitingObservational study
Tissue, Blood, and Body Fluid Sample Collection From Patients With Hematologic Cancer
Chronic Myeloproliferative Disorders, Leukemia
RecruitingPhase 1/2
Dose Escalation and Dose Expansion Study of MDX2003 in Patients With Different Types of Lymphoma
Lymphoma, Waldenström Macroglobulinemia (WM)
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.
The record lists no contact. Use the official record to reach the sponsor.
14 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing APG2575 400 mg, APG2575 600 mg and APG2575 800 mg in people with Waldenstrom Macroglobulinemia, run by Ascentage Pharma Group Inc. at 14 sites in 3 countries.
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 40 inclusion and 24 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: finished, as of the sponsor's last update on 19 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in China, United States, Australia. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Toxicity Endpoint: dose limiting toxicity (DLT) (time frame: 42 days). The study lists 2 primary outcomes in all. 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 19 Aug 2025.