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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04260217




Registration number
NCT04260217
Ethics application status
Date submitted
5/02/2020
Date registered
7/02/2020
Date last updated
25/10/2023

Titles & IDs
Public title
APG-2575 Single Agent or in Combination With Ibrutinib or Rituximab in Patients With Waldenström Macroglobulinemia
Scientific 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)
Secondary ID [1] 0 0
APG2575WU101
Universal Trial Number (UTN)
Trial acronym
MAPLE-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Waldenstrom Macroglobulinemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - APG2575 400 mg
Treatment: Drugs - APG2575 600 mg
Treatment: Drugs - APG2575 800 mg

Experimental: APG2575 400 mg - APG2575 400mg ramp up arm

Experimental: APG2575 600 mg - APG2575 600 mg ramp up arm

Experimental: APG2575 800 mg arm - APG2575 800 mg arm ramp up


Treatment: Drugs: APG2575 400 mg
APG2575 400 mg

Treatment: Drugs: APG2575 600 mg
APG2575 600 mg

Treatment: Drugs: APG2575 800 mg
APG2575 800 mg
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Primary Toxicity Endpoint: dose limiting toxicity (DLT)
Timepoint [1] 0 0
42 days
Primary outcome [2] 0 0
Maximally tolerated dose (MTD)
Timepoint [2] 0 0
42 days

Eligibility
Key inclusion criteria
- Criteria for inclusion:

Patients must meet all of the following inclusion criteria to be eligible for participation
in this study:

1. Local confirmed clinicopathological diagnosis of WM in accordance with the consensus
panel of the Second International Workshop on WM (Owen 2003).

2. 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.

3. 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.

4. For Arm B only: Previously untreated WM.

5. For Arm C only: Have received at least one prior therapy, relapsed or refractory WM.

6. Adequate hematologic function defined as:

1. ANC =1.0 x 109/L independent of growth factor support within 7 days of the first
dose with study drug.

2. Hemoglobin =9 g/dL without transfusion or growth factor support within 7 days of
the first dose of study drug.

3. Platelet count = 75 x 109/L without transfusion support within 7 days of the
first dose of study drug.

7. Adequate hepatic and renal function defined as:

1. AST and ALT < 2.5 x ULN (upper limit of normal)

2. Glomerular filtration rate (GFR) >30mL/min

3. Bilirubin< 1.5 x ULN

8. PT/INR =1.5 x ULN and PTT (aPTT) =1.5 x ULN.

9. =18 years of age.

10. Eastern Cooperative Oncology Group (ECOG) =1.

11. Life expectancy=3 months.

12. 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.

13. 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):

1. 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:

1. Unintentional weight loss =10% within the previous 6 months prior to Screening

2. Fevers higher than 100.5°F or 38.0°C for 2 or more weeks prior to Screening
without evidence of infection

3. Night sweats for more than 1 month prior to Screening without evidence of
infection

2. Clinically relevant fatigue which is not relieved by rest due to WM

3. Symptomatic hyperviscosity or serum viscosity levels greater than 4.0 centipoises

4. Lymphadenopathy which is either symptomatic or bulky (=5cm in maximum diameter)

5. Symptomatic hepatomegaly and/or splenomegaly and/or organ tissue infiltration

6. Peripheral neuropathy due to WM

7. Symptomatic cryoglobulinemia

8. Cold agglutinin anemia

9. IgM related immune hemolytic anemia and/or thrombocytopenia

10. Nephropathy related to WM

11. Amyloidosis related to WM

12. Hemoglobin =10g/dL

13. Platelet count <100 x109/L

14. Serum monoclonal protein >5g/dL, with or without overt clinical symptoms.

15. Any other condition or circumstance that would, in the opinion of the investigator,
make the patient unsuitable for participation in the study.
Minimum age
18 Years
Maximum age
95 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Criteria for exclusion:

Patients who meet any of the following exclusion criteria are not to be enrolled in this
study:

1. For Arm A only: Patients who have never been treated with ibrutinib.

2. For Arm B only: Patients who have previously received any treatment for WM.

3. For Arm C only:

1. Patients who have previously been treated with ibrutinib or other BTK inhibitor.

2. 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.

3. Rituximab treatment within the last 12 months before the first dose of study
drug.

4. Known anaphylaxis or IgE-mediated hypersensitivity to murine proteins or to any
component of rituximab.

4. 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.

5. 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).

6. Failure to have fully recovered (i.e., =Grade 1 toxicity) from the reversible effects
of prior treatment for WM.

7. 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.

8. 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.

9. History of active or chronic infection with hepatitis C virus (HCV) or hepatitis B
virus (HBV) defined by positive polymerase chain reaction (PCR).

10. 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.

11. 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.

12. Recent infection requiring systemic treatment that was completed=14 days before the
first dose of study drug.

13. Any uncontrolled active systemic infection.

14. Any concurrent malignancy.

15. Concomitant use of warfarin or other Vitamin K antagonists (eg. phenoprocoumon).

16. Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor.

17. Known bleeding disorders (eg, von Willebrand's disease) or hemophilia.

18. History of stroke or intracranial hemorrhage within 12 months prior to enrollment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/05/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/12/2025
Actual
Sample size
Target
123
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
St. Vincent Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3065 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
China
State/province [6] 0 0
Guangdong
Country [7] 0 0
China
State/province [7] 0 0
Shanghai
Country [8] 0 0
China
State/province [8] 0 0
Beijing
Country [9] 0 0
China
State/province [9] 0 0
Hangzhou
Country [10] 0 0
China
State/province [10] 0 0
Nanjing
Country [11] 0 0
China
State/province [11] 0 0
Suzhou
Country [12] 0 0
China
State/province [12] 0 0
Tianjin
Country [13] 0 0
China
State/province [13] 0 0
Zhengzhou

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Ascentage Pharma Group Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04260217
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Angela Kaiser
Address 0 0
Country 0 0
Phone 0 0
310-509-0357
Fax 0 0
Email 0 0
angela.kaiser@ascentage.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04260217