Clinical Study of CWP232291 in Relapsed or Refractory Myeloma Patients
- Conditions
- Multiple Myeloma
- Registration Number
- NCT02426723
- Lead Sponsor
- JW Pharmaceutical
- Brief Summary
This is a Phase 1a/1b, multicenter, open-label, two-part study in subjects with relapsed or refractory MM:
* Phase 1a: single agent CWP232291. Dose-finding followed by cohort expansion at the maximum tolerated dose (MTD) or optimal dose as determined by the Safety Review Committee (SRC).
* Phase 1b: CWP232291 in combination with lenalidomide and dexamethasone. Dose-finding followed by cohort expansion at the combination therapy MTD or optimal dose as determined by the SRC.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 25
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Able to understand and then sign an informed consent form (ICF) prior to initiation of any study-specific procedure and treatment.
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≥ 18 years of age.
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Confirmed measurable 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.
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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.
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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.
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Eastern Cooperative Oncology Group (ECOG) performance score 0-2 (Appendix 3).
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Adequate bone marrow function:
- Absolute neutrophil count (ANC) ≥ 1000/mm3, independent of growth factor support;
- Platelet count ≥ 75,000/mm3;
- Hb ≥ 9 g/dL (independent of transfusions or erythropoiesis-stimulating agents [ESA]).
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Adequate renal function:
- Serum creatinine ≤ 2.5 mg/dL;
- Creatinine clearance (CrCl) ≥ 60 mL/minute (Cockcroft-Gault).
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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.
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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 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. 13. Able to adhere to the study visit schedule and other protocol requirements.
- Chemotherapy or immunotherapy < 5 half-lives prior to screening.
- Not recovered to Grade 1 from adverse effects of prior myeloma therapy or radiotherapy prior to screening.
- 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.
- 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) < 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 < 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 < 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method Recommended dose of Phase 2 trial of CWP232291 up to 4 weeks
- Secondary Outcome Measures
Name Time Method Cmax as a pharmacokinetic parameter of 'CWP232291' Predose, 0.25, 0.5, 0.75, 1, 1.5 , 2 , 4 , 8, 12, 24 hours after the start of infusion Peak plasma concentration(Cmax) of 'CWP232291'
AUC as a pharmacokinetic parameter of 'CWP232291' Predose, 0.25, 0.5, 0.75, 1, 1.5 , 2 , 4 , 8, 12, 24 hours after the start of infusion Area under the plasma concentration versus time curve (AUC) of 'CWP232291'
Cmax as a pharmacokinetic parameter of metabolites of ' CWP232204' Predose, 0.25, 0.5, 0.75, 1, 1.5 , 2 , 4 , 8, 12, 24 hours after the start of infusion Peak Plasma Concentration (Cmax) of metabolites of 'CWP232291'
AUC as a pharmacokinetic parameter of metabolites of ' CWP232204' Predose, 0.25, 0.5, 0.75, 1, 1.5 , 2 , 4 , 8, 12, 24 hours after the start of infusion Area under the plasma concentration versus time curve (AUC) of metabolites of 'CWP232291'
Trial Locations
- Locations (4)
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Seoul St.Mary's Hospital
🇰🇷Seoul, Korea, Republic of
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Yonsei Severance Hospital
🇰🇷Seoul, Korea, Republic of