A Study of Safety, Tolerability, Pharmacokinetic and Pharmacodynamics (PK/PD) in Patients With Hematologic Malignancies

Overview

About this study

The purpose of this study is to evaluate the safety and tolerability of APG-2575 as well as dose escalation and dose expansion stages.

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. Please contact the study team to discuss whether or not you are eligible to participate in a study.

Inclusion Criteria:

  • Age ≥ 18 years old.
  • Histologically confirmed diagnosis of either one of the B-cell hematologic malignancies including multiple myeloma, chronic lymphocytic leukemia, lymphoplasmacytic lymphoma, and non-Hodgkin's lymphoma such as mantle cell lymphoma, diffuse large B cell lymphoma, Waldenstrom macroglobulinemia (WM) and acute myeloid leukemia
  • Patient must have relapsed or refractory to, intolerant to, or are considered ineligible for therapies known to provide clinical benefit. In addition, AML Patients will be eligible if they have failed standard induction regimen, are not considered candidate for further chemotherapy or stem cell transplantation or have primary refractory AML.
  • Life expectancy ≥ 3 months.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS):
    • 0 -1 in dose escalation;
    • 0-2 in dose expansion.
  • QTc interval ≤ 450ms in males, and ≤ 470ms in females.
  • Adequate bone marrow function independent of growth factor:
    • Absolute neutrophil count (ANC) ≥1.0 X 10^9/L;
    • Hemoglobin ≥ 8.0 g/dL;
    • Platelets count ≥ 30 X 10^9/L (entry platelet count must be independent of transfusion within 7 days of first dose).
  • Adequate renal and liver function as indicated by:
    • Serum creatinine ≤ 1.5 x ULN; if serum creatinine is > 1.5 X ULN, creatinine clearance must be ≥ 60 mL/min;
    • Total bilirubin ≤1.5 x ULN, except subjects with known Gilbert’s syndrome;
    • AST and ALT <2.5 x ULN;
    • Alkaline phosphatase < 2.5 x ULN and < 5 x for bone metastases & / or no hepatic parenchymal metastases on screening radiographic examination;
    • INR, PT or aPTT ≤1.5 X ULN unless the subject is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants.
  • Willingness to use contraception by a method that is deemed effective by the investigator by both males and female patients of child bearing potential (postmenopausal women must have been amenorrheal for at least 12 months to be considered of non-childbearing potential) and their partners throughout the treatment period and for at least three months following the last dose of study drug.
  • 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 procedures).
  • Willingness and ability to comply with study procedures and follow-up examination.

Exclusion Criteria:

  • Prior history of allogeneic cell transplant.
  • Subjects have been diagnosed with Burkitt's lymphoma, Burkitt-like lymphoma, or lymphoblastic lymphoma/leukemia.
  • Received chemotherapy within 14 days (42 days for nitrosoureas or mitomycin C) prior to entering the study.
  • Received biologic (< 28 days), small molecule targeted therapies (< 5 half-life) or other anti-cancer therapy within 21 days of study entry.
  • Radiation within 14 days of study entry, thoracic radiation within 28 days of study entry.
  • Has gastrointestinal conditions that could affect the absorption of APG-2575 in the opinion of the Investigator.
  • Has known active central nervous system (CNS) involvement.
  • Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not recover to ≤ Grade 1 except alopecia or neuropathy.
  • Concurrent treatment with an investigational agent, 14 days for small molecular agents and/or 28 days for biologics treatment prior to the first dose of therapy.
  • Failure to recover adequately, as judged by the investigator, from prior surgical procedures. Patients with active wound healing, patients who have had major surgery within 28 days from study entry, and patients who have had minor surgery within 14 days of study entry.
  • Unstable angina, myocardial infarction, or a coronary revascularization procedure within 180 days of study entry.
  • Active rheumatoid arthritis (RA), active inflammatory bowel disease, chronic infections, or any other disease or condition associated with chronic inflammation.
  • Active infection requiring systemic antibiotic/ antifungal medication, known clinically active hepatitis B or C infection, or on antiretroviral therapy for HIV disease.
  • Known or suspected Wilson's Disease, or other conditions that affect copper accumulation or regulation.
  • Uncontrolled concurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with the study requirements.
  • Prior use of a Bcl-2 inhibitor
  • History of secondary active malignancies within the past 2 years prior to1st dose of study drug. However, adequately treated superficial skin cancer other than melanoma, in situ cervix cancer more than 4 weeks prior to1st dose of study drug, or prostate cancer not requiring any treatment and under surveillance will not be considered exclusionary.
  • Any other condition or circumstance that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.

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

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Jose Leis, M.D., Ph.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Sikander Ailawadhi, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Sameer Parikh, M.B.B.S.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

International patient clinical studies questions