Clinical Trial 19001

Cancer Type: Malignant Hematology
Interventions:CC-5013 (Lenalidomide); CWP232291; Dexamethasone; Lenalidomide (Revlimid)

Study Type: Treatment
Phase of Study: Phase I
Investigators:

  • Kenneth Shain

Overview

Study Title

A Phase 1a/1b Multicenter, Open Label, Dose-Finding Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of CWP232291 Administered Intravenously Either Alone or in Combination with Lenalidomide and Dexamethasone in Subjects with Relapsed or Refractory Myeloma (MM)

Summary

The purpose of this study is to examine CWP232291, an investigational drug that may treat relapsed or refractory multiple myeloma (MM).

Objective

STUDY OBJECTIVES AND PURPOSE Primary Objective: The primary objective of this study is to determine the recommended Phase 2 dose (RP2D) of CWP232291 for subjects with relapsed or refractory myeloma, when administered either alone (Phase 1a) or in combination with lenalidomide and dexamethasone (Phase 1b). Secondary Objectives: In both Phase 1a and Phase 1b for subjects with MM, the secondary objectives are: To determine the safety and tolerability of each regimen evaluated. To characterize the pharmacokinetic (PK) profile of CWP232291 and CWP232204 administered alone, and in combination with lenalidomide and dexamethasone. To evaluate effects of CWP232291 on relevant biomarkers alone, and in combination with lenalidomide and dexamethasone. To assess the preliminary anticancer efficacy of CWP232291 alone, and in combination with lenalidomide and dexamethasone.

Inclusion Criteria

  • Able to understand and then sign an informed consent form (ICF) prior to initiation of any study-specific procedure and treatment.
  • ≥ 18 years of age.
  • Confirmed measurable multiple myeloma (MM) based on the following: Serum M component (≥ 0.5 g/dL), or - Urine M protein ≥ 200 mg/24 hours), or - Serum immunoglobulin free light chains ≥ 10 mg/dL and abnormal serum immunoglobulin kappa/lambda free light chain ratio), or - Non-secretory disease measurable with bone marrow biopsy or radiography.
  • Failed 2 or more prior standard MM therapies, and >100 days post autologous bone marrow transplant prior to first dose for transplanted subjects. Prior lenalidomide is permitted.
  • In the absence of rapidly progressing disease, the interval from prior treatment to time of study drug administration should be ≥ 2 weeks for cytotoxic agents or at least 5 half-lives for noncytotoxic agents. Persistent clinically significant toxicities from prior chemotherapy or radiotherapy must not be greater than Grade 1.
  • Eastern Cooperative Oncology Group (ECOG) performance score 0-2.
  • Adequate bone marrow function: Absolute neutrophil count (ANC) ≥ 1000/mm^3, independent of growth factor support; Platelet count ≥ 75,000/mm^3; Hb ≥ 9 g/dL (independent of transfusions or erythropoiesis-stimulating agents [ESA]).
  • Adequate renal function: Serum creatinine ≤ 2.5 mg/dL; Creatinine clearance (CrCl) ≥ 60 mL/minute (Cockcroft-Gault).
  • Adequate hepatic function: Total bilirubin > Women of child-bearing potential (i.e., women who are premenopausal or not surgically sterile): Two effective forms of contraception (abstinence, intrauterine device, oral contraceptive, or double barrier device) from the time of informed consent and until at least 4 weeks after discontinuing study drugs, and Negative serum or urine pregnancy tests during screening and then within 3 days prior to Day 1. 12. Sexually active men - effective contraceptive methods in subject and partner from the time of informed consent and until ≥ 4 weeks after discontinuing study drugs. <<*<< Able to adhere to the study visit schedule and other protocol requirements.

  • Exclusion Criteria

  • Chemotherapy or immunotherapy > Not recovered to Grade 1 from adverse effects of prior myeloma therapy or radiotherapy prior to screening.
  • Systemic corticosteroids less than or equal to 1 week prior to Day 1 in Phase 1a. Participants may receive stable physiologic replacement doses of glucocorticoids (up to the equivalent of 10 mg daily prednisone) as maintenance therapy for adrenal insufficiency.
  • Uncontrolled intercurrent illness including infections and psychiatric illness/social situations that may limit compliance with protocol requirements or the evaluation of study drugs.
  • Active cardiovascular disease including myocardial infarction (MI) less than 6 months of screening, symptomatic coronary artery disease (CAD), arrhythmias, hypertension, or heart failure not controlled by medication.
  • History of deep venous thrombosis and pulmonary embolism (Phase 1b).
  • Anticoagulants less than 7 days prior to Day 1. Aspirin is permitted in Phase 1b per standard of care with lenalidomide-based therapy.
  • Active central nervous system (CNS) disease.
  • Known positive status for human immunodeficiency virus (HIV) and/or active hepatitis B or C.
  • Pregnant or nursing women.
  • History of hypersensitivity to lenalidomide (Part B only).
  • History of other active malignancies less than 3 years prior to screening except basal cell carcinoma, low grade Gleason score ≤ 6 prostate cancer that has been removed with undetectable prostate-specific antigen (PSA), and in situ cervical carcinoma.