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
Elisabet E. Manasanch
The goal of this clinical research study is to find the highest tolerable dose of CWP232291 when given alone or in combination with lenalidomide and dexamethasone. The safety of this drug and drug combination will also be studied.
Disease Group: Myeloma
Treatment Agent: CWP232291,Dexamethasone,Lenalidomide
Treatment Location: Both at MDACC & and Other Sites
Sponsor: JW Pharmaceutocal Corporation
Primary Objective 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 Objective In both Phase 1a and Phase 1b for subjects with Multiple Myeloma, 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.
IRB Review and Approval Date: 08/27/2015
Recruitment Status: Open
Projected Accrual: 36-69
1) Able to understand and then sign an informed consent form (ICF) prior
to initiation of any study-specific procedure and treatment.
2) >/= 18 years of age.
3) Confirmed measurable MM based on the following: *Serum M component (>/= 0.5 g/dL), or *Urine M protein >/= 200 mg/24 hrs), 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
4) 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.
5) 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.
6) Eastern Cooperative Oncology Group (ECOG) performance score 0-2.
7) Adequate bone marrow function: *Absolute neutrophil count (ANC) >/= 1000/mm^3; * Platelet count >/= 50,000/mm^3; * Hb >/= 8 g/dL.
8) Adequate renal function: *Serum creatinine </= 2.5 mg/dL; *Creatinine clearance (CrCl) >/=60 mL/minute (Cockcroft-Gault).
9) Adequate hepatic function:Total bilirubin < 2.5 x upper limit of normal (ULN); direct bilirubin < 2 x ULN for Gilbert’s syndrome; *Alkaline phosphatase (AP) </= 2.5 x ULN, unless considered due to organ leukemic involvement; • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) </= 3 x ULN.
10) Women of child-bearing potential (ie, 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 (Phase 1a).* Negative serum or urine pregnancy tests within 10 to 14 days and the second test within 24 hours prior to starting lenalidomide therapy (Phase 1b).
11) Sexually active men - effective contraceptive methods in subject and partner from the time of informed consent and until >/= 4 weeks after discontinuing study drugs.
12) Able to adhere to the study visit schedule and other protocol requirements.
1) Chemotherapy or immunotherapy < 5 half-lives prior to screening.
2) Not recovered to Grade 1 from adverse effects of prior myeloma therapy or radiotherapy prior to screening.
3) Systemic corticosteroids < 1 week prior to Day 1 in Phase 1a. Subjects may receive stable physiologic replacement doses of glucocorticoids (up to the equivalent of 10 mg daily prednisone) as maintenance therapy for adrenal insufficiency.
4) Uncontrolled intercurrent illness including infections and psychiatric illness/social situations that may limit compliance with protocol requirements or the evaluation of study drugs.
5) Active cardiovascular disease including myocardial infarction (MI) < 6 months of screening, symptomatic coronary artery disease (CAD), arrhythmias, hypertension, or heart failure not controlled by medication.
6) Active central nervous system (CNS) disease.
7) Known positive status for human immunodeficiency virus (HIV) and/or active hepatitis B or C.
8) Pregnant or nursing women.
9) History of hypersensitivity to lenalidomide (Part B only).
10) History of other active malignancies < 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.
Information and next steps
Elisabet E. Manasanch
For general questions about clinical trials: