A Study of APG-2575 Alone or in Combination with Other Therapeutic Agents to Treat Relapsed and/or Refractory Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)


About this study

The purpose of this study is to assess the safety and tolerability, identify dose-limiting toxicities (DLT) and determine the maximum tolerated dose (MTD) / recommended phase 2 dose (RP2D) of APG-2575.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

- 1. ≥18 years of age. 2. Histologically confirmed chronic lymphocytic leukemia (CLL) or
small lymphocytic leukemia (SLL) according to the 2018 international workshop (IW) CLL
criteria who must have relapsed or be refractory to at least one prior therapy for
CLL/SLL and require treatment by 2018 IWCLL criteria.

3. ECOG) ≤2. 4. Patient must have objectively documented evidence of disease
progression prior to study entry such as: escalating lymphocytes count with an
increase > 50% over a period of two months or doubling time in less than 6 months;
enlarging adenopathy or splenomegaly; increasing cytopenias; clinical B symptoms
-night sweats, fatigue, > 1% weight loss in 6 months, fevers > 100.50F for ≥ one month
without infection.

5. In Part 1 of the APG-2575 monotherapy dose escalation portion, patients eligible
for dose expansion at doses lower than MTD will have received ≤ 3 prior systemic lines
of therapy.

6. Adequate bone marrow function independent of growth factor:

1. Absolute neutrophil count (ANC)≥1.0× 109/L in patient without bone marrow
involvement. This criterion does not apply to patients with bone marrow
involvement by CLL/SLL.

2. Platelets count ≥30 x 109/L (entry platelet count must be independent of
transfusion within 7 days of first dose of study drug).

7. Adequate renal and hepatic function as indicated by:

a. Serum creatinine ≤1.5×upper limit of normal (ULN); if serum creatinine is >1.5×ULN,
creatinine clearance must be ≥ 50 mL/min, calculated using the Cockcroft and Gault
formula(140-Age)x mas (kg)/(72x creatinine mg/dL); multiply by 0.85 if female
(Cockcroft 1976) b. Total bilirubin ≤1.5 x ULN, except patients with known Gilbert's
syndrome. c. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) <2.5
x ULN, Alkaline phosphatase<2.5×ULN d. International normalized Ratio (INR),
Prothrombin Time (PT) or Activated Partial Thromboplastin time (APTT)≤1.5×ULN unless
the patient is receiving anticoagulant therapy as long as PT or APTT is within
therapeutic range of intended use of anticoagulants.

8. Females of childbearing potential (i.e. not postmenopausal for at least 2 years or
surgically sterile) must have negative results for pregnancy test performed:

a. At Screening on a serum sample obtained within 14 days prior to the first study
drug administration b. Prior to dosing on a urine sample obtained on the first day of
study drug administration, if it has been>7 days since obtaining the serum pregnancy
test results.

9. Females of childbearing potential and non-sterile males must practice at least one
of the following methods of birth control with partner(s) throughout the study and for
90 days after discontinuing study drug:

1. Total abstinence from sexual intercourse as the preferred lifestyle of the
patient; periodic abstinence is not acceptable;

2. Surgically sterile partner(s); acceptable sterility surgeries are: vasectomy,
bilateral tubal ligation, bilateral oophorectomy or hysterectomy;

3. Intrauterine device (IUD);

4. Double-barrier method (contraceptive sponge, diaphragm or cervical cap with
spermicidal fellies or cream AND a condom);

5. Hormonal contraceptives (oral, parenteral, vaginal ring or transdermal) for at
least 3 months prior to study drug administration.

If hormonal contraceptives are used, the specific contraceptive must have been
used for at least 3 months prior to study drug administration.

10. Male patients must refrain from sperm donation, from initial study drug
administration until 90 days after the last dose of study drug.

11. Ability to understand and willingness to sign a written informed consent form
(the consent form must be signed by the patient prior to any study-specific

12. Willingness and ability to comply with study procedures and follow-up

Exclusion Criteria:

- 1. Patient has undergone allogeneic stem cell transplant < 90 days 2. Patient has
active graft-versus-host disease or require immunosuppressive therapy.

3. Richter's Syndrome. 4. Prior anti-Bcl-2 treatment (except patients who discontinued
treatment for reasons other than disease progression) 5. For combination cohorts:

1. In the acalabrutinib and APG-2575 cohort, patients who are on anticoagulants or
patients that discontinued due to acalabrutinib toxicity (Note: Patients who
received a BTK inhibitor therapy may participate whether, or not, they progressed
following BTK inhibitor treatment).

2. Prior CDK-9 inhibitor in the voruciclib plus APG-2575 cohort 6. Known human
immunodeficiency virus syndrome (HIV) infection 7. Known active hepatitis B
infection, as defined seropositivity for Hep B surface antigen (HBsAg) or known
hepatitis C infection as determined by hepatitis C antibody with elevated liver
enzymes as defined in the inclusion criteria or any other evidence of active
hepatitis C such as currently on treatment 8. Has known central nervous system
(CNS) involvement. 9. Prior malignancy that required treatment and has shown
recurrence within 2 years of screening (except for non-melanoma skin cancer or
adequately treated carcinoma in situ of cervix or breast). Cancer treated within
2 years with curative intent and without recurrence as well as prostate cancer on
active surveillance are allowed.

10. Concurrent treatment with an investigational agent, received biologics (≤28
days), or small molecule targeted therapies (≤5 half-life) or other anti-cancer
therapies (including chemotherapy) ≤14 days of first dose of study drug 11.
Patient is pregnant or breast feeding 12. Has received the following within 7
days prior to the first dose of study drug:

1. Steroid therapy at a dose greater than prednisone 20 mg daily (or equivalent) for
anti-neoplastic intent;

2. CYP3A inhibitors such as fluconazole, ketoconazole, and clarithromycin;

3. Potent CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's
wort; 13. Radiation within 14 days of study entry 14. Continuance of toxicities
due to prior radiotherapy or chemotherapy agents that have not recovered to ≤
grade 1 or baseline, except alopecia or neuropathy.

15. Failure to recover adequately, as judged by the investigator, from prior
surgical procedures. Patient with active wound healing, patients who have had
major surgery within 28 days from 1st dose of study drug 16. Has a cardiovascular
disability status of New York Heart Association Class ≥ 2. Class 2 is defined as
cardiac disease in which patients are comfortable at rest but ordinary physical
activity results in fatigue, palpitations, dyspnea or anginal pain.

17. Unstable angina or myocardial infarction within 3 months of enrollment 18.
QTc interval> 480ms (Bazett or Fredericia formulae) or other remarkable abnormal
ECG findings, including second-degree type II atrioventricular block,
third-degree atrioventricular block or bradycardia (ventricular rate of less than
50 beats per minute).

19. Has gastrointestinal conditions that could affect the absorption of APG-2575
in the opinion of the Investigator.

20. Uncontrolled concurrent illness including, but not limited to: uncontrolled
diabetes mellitus, symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
limit compliance with the study requirements.

21. Any other condition or circumstance that would, in the opinion of the
investigator, make the patient unsuitable for participation in the study.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 9/15/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Sikander Ailawadhi, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

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