Clinical Study of CWP232291 in Relapsed or Refractory Myeloma Patients

• ClinicalTrials.gov Identifier: NCT02426723
• Recruitment Status: Completed
• First Posted: April 27, 2015
• Last Update Posted: May 17, 2019
• Sponsor: JW Pharmaceutical
• Information provided by (Responsible Party): JW Pharmaceutical

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Drug: Phase 1a: CWP232291; Drug: Phase 1b: CWP232291, Lenalidomide, Dexamethasone	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official 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)
• Actual Study Start Date: October 19, 2015
• Actual Primary Completion Date: October 8, 2018
• Actual Study Completion Date: October 26, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: CWP232291; Phase 1a: single administration of CWP232291 , Phase 1b: CWP232291 combination with Lenalidomide and Dexamethasone	Drug: Phase 1a: CWP232291; CWP232291 administered alone twice weekly every 4 weeks.; Drug: Phase 1b: CWP232291, Lenalidomide, Dexamethasone; CWP232291 administered twice weekly every 4 weeks. Lenalidomide and Dexamethasone administered per standard therapy.

Outcome Measures

Primary Outcome Measures :

1. Recommended dose of Phase 2 trial of CWP232291 [ Time Frame: up to 4 weeks ]

Secondary Outcome Measures :

1. Cmax as a pharmacokinetic parameter of 'CWP232291' [ Time Frame: 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'
2. AUC as a pharmacokinetic parameter of 'CWP232291' [ Time Frame: 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'
3. Cmax as a pharmacokinetic parameter of metabolites of ' CWP232204' [ Time Frame: 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'
4. AUC as a pharmacokinetic parameter of metabolites of ' CWP232204' [ Time Frame: 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'

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

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 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.
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 (Appendix 3).

7. 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]).

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.

11. 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.

Exclusion Criteria:

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. History of deep venous thrombosis and pulmonary embolism (Phase 1b).
7. Anticoagulants < 7 days prior to Day 1. Aspirin is permitted in Phase 1b per standard of care with lenalidomide-based therapy.
8. Active central nervous system (CNS) disease.
9. Known positive status for human immunodeficiency virus (HIV) and/or active hepatitis B or C.
10. Pregnant or nursing women.
11. History of hypersensitivity to lenalidomide (Part B only)
12. 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.

Contacts and Locations

Locations

United States, Texas

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

Korea, Republic of

Seoul National University Hospital

Seoul, Korea, Republic of

Seoul St.Mary's Hospital

Seoul, Korea, Republic of

Yonsei Severance Hospital

Seoul, Korea, Republic of

Sponsors and Collaborators

JW Pharmaceutical

Investigators

• Principal Investigator: Chang-Ki Min, MD; Seoul St. Mary's Hospital
• Principal Investigator: Sung-Soo Yoon, MD; Seoul National University Hospital
• Principal Investigator: Jin Seok Kim, MD; Severance Hospital
• Principal Investigator: Elisabet Manasanch, MD; M.D. Anderson Cancer Center

More Information

• Responsible Party: JW Pharmaceutical
• ClinicalTrials.gov Identifier: NCT02426723
• Other Study ID Numbers: JW-231MM-102
• First Posted: April 27, 2015
• Last Update Posted: May 17, 2019
• Last Verified: May 2019

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Dexamethasone; Lenalidomide; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents