Clinical Trials /

Clinical Study of CWP232291 in Acute Myeloid Leukemia Patients

NCT03055286

Description:

This is a multicenter (S. Korea/US), Phase Ib, open-label, dose-finding study to assess safety, PK, PD, and preliminary efficacy of CWP232291 administered in combination with ara-C in subjects with relapsed or refractory AML. The primary objectives in phase 2a is to assess the efficacy of CWP232291 administered in combination with cytarabine (response rate complete remission [RR-CR]/complete remission with incomplete blood count recovery [CRi]/partial remission [PR]).

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Clinical Study of CWP232291 in Acute Myeloid Leukemia Patients
  • Official Title: A Phase 1b/2a Clinical Study of CWP232291 in Combination With Cytarabine in Subjects With Relapsed or Refractory Acute Myeloid Leukemia (AML)

Clinical Trial IDs

  • ORG STUDY ID: JW-231A-103
  • NCT ID: NCT03055286

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
CWP232291CWP232291 in combination with cytarabine (ara-C)

Purpose

This is a multicenter (S. Korea/US), Phase Ib, open-label, dose-finding study to assess safety, PK, PD, and preliminary efficacy of CWP232291 administered in combination with ara-C in subjects with relapsed or refractory AML. The primary objectives in phase 2a is to assess the efficacy of CWP232291 administered in combination with cytarabine (response rate complete remission [RR-CR]/complete remission with incomplete blood count recovery [CRi]/partial remission [PR]).

Trial Arms

NameTypeDescriptionInterventions
CWP232291 in combination with cytarabine (ara-C)Experimental
  • CWP232291

Eligibility Criteria

        Inclusion Criteria:

          1. Understands and is willing to sign an informed consent form (ICF) prior to initiation
             of any study-specific procedure.

          2. 18 years of age at the time of consenting.

          3. A pathologically confirmed diagnosis of AML by World Health Organization (WHO)
             classification that is progressing.

          4. Has failed (refractory) or relapsed after no more than 2 prior regimens, and for whom
             for whom no other standard therapy options are available.

          5. Subjects with prior autologous and allogeneic hematopoietic stem cell transplantation
             (allo HSCT) are eligible.

          6. Adequate laboratory results including the following:

               -  Serum creatinine ≤ 2.0 mg/dL

               -  Total bilirubin ≤ 1.5 x upper limit of institutional normal (ULN), unless due to
                  Gilbert's syndrome

               -  Aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 3 x ULN, unless due
                  to organ leukemic involvement

          7. Eastern Cooperative Oncology Group (ECOG) performance score 0-2.

          8. The subject should be off any anticancer therapy including chemotherapy,
             immunotherapy, radiotherapy, hormonal, biologic or any investigational agents for at
             least 14 days or 5 half lives, whichever is greater, prior to enrollment with the
             exception of hydroxyurea. All prior treatment-related non-hematologic toxicities must
             have resolved to ≤ grade 2 prior to screening.

          9. Female subject of childbearing potential (ie, premenopausal or not surgically sterile)
             must agree to use effective contraception from Day 1 until 28 days after the last dose
             of study drug, and have a negative serum or urine pregnancy test within 2 weeks prior
             to Day 1. Sexually active male subjects must also use effective contraception from Day
             1 until 90 days after the last dose of any study drug.

         10. Female subject must agree not to breastfeed at screening and throughout the study
             period and for 45 days after the final study drug administration. Female subject must
             not donate ova starting at screening and throughout the study period and for 45 days
             after the final study drug administration.

         11. Male subject must not donate sperm starting at screening and throughout the study
             period and for 90 days after the final study drug administration.

         12. Agree to adhere to all study protocol requirements.

        Exclusion Criteria:

          1. Subject has BCR-ABL-positive leukemia (Chronic myeloid leukemia [CML] in blast
             crisis).

          2. Subject is diagnosed as acute promyelocytic leukemia (APL).

          3. Subject has AML secondary to prior chemotherapy.

          4. Subject has active clinically significant graft versus host disease (GVHD) or is on
             treatment with systemic corticosteroids for GVHD (except grade 1 skin GVHD). At least
             3 months must have elapsed since completion of allogeneic stem cell transplantation.

          5. Subject had a myocardial infarction within 6 months of enrollment, heart failure (New
             York Heart Association (NYHA) Class III or IV), uncontrolled angina, severe
             uncontrolled ventricular arrhythmias, left ventricular ejection fraction (LVEF) ≤ 40%
             or evidence of acute ischemia or active conduction system abnormalities.

          6. Presence of a systemic fungal, bacterial, viral or other infection not controlled
             (defined as exhibiting ongoing signs/symptoms related to the infection and without
             improvement, despite appropriate antibiotics or other treatment).

          7. Known in tolerance and allergy to cytarabine.

          8. Active central nervous system (CNS) disease.

          9. Known positive status for human immunodeficiency virus (HIV) and/or active hepatitis B
             or C.

         10. Prior exposure to CWP232291.

         11. Pregnant or breastfeeding women.

         12. Suitable for imminent bone marrow transplant, or within 4 weeks of one.

         13. Major surgery within 4 weeks prior to the first study dose.

         14. Concurrent other malignancy, unless the patient has been disease-free for at least
             five years following curative intent therapy, with the following exceptions: (1)
             adequately treated in-situ carcinoma of cervix; (2) localized basal cell or squamous
             cell carcinoma of skin; (3) previous malignancy confined and treated locally (surgery
             or other modality) with curative intent.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended Phase 2 dose
Time Frame:up to 4 weeks
Safety Issue:
Description:To be determinded Recommended Phase 2 dose (RP2D) of CWP232291 in combination with cytarabine (ara-C), administered to subjects with relapsed or refractory AML.

Secondary Outcome Measures

Measure:Cmax as a Pharmacokinetic (PK) assessments for CWP232291
Time Frame:3rd Cycle (each cycle = 28 days), Cycle 1 Day 1: Pre, 0.5hr, 1hr, 2hr, 3hr, 4hr, 5hr, 8hr, and 24hr after the start of infusion in Part A and at Cycle 1 Day 1: Pre, 2hr, 4hr, 8hr, and 24hr after the start of infusion in Part B.
Safety Issue:
Description:maximum plasma concentration (Cmax)
Measure:tmax as a Pharmacokinetic (PK) assessments for CWP232291
Time Frame:3rd Cycle (each cycle = 28 days), Cycle 1 Day 1: Pre, 0.5hr, 1hr, 2hr, 3hr, 4hr, 5hr, 8hr, and 24hr after the start of infusion in Part A and at Cycle 1 Day 1: Pre, 2hr, 4hr, 8hr, and 24hr after the start of infusion in Part B.
Safety Issue:
Description:time to maximum observed plasma concentration (tmax)
Measure:AUC0-t as a Pharmacokinetic (PK) assessments for CWP232291
Time Frame:3rd Cycle (each cycle = 28 days), Cycle 1 Day 1: Pre, 0.5hr, 1hr, 2hr, 3hr, 4hr, 5hr, 8hr, and 24hr after the start of infusion in Part A and at Cycle 1 Day 1: Pre, 2hr, 4hr, 8hr, and 24hr after the start of infusion in Part B.
Safety Issue:
Description:area under the time-concentration curve from time zero to the last measurable concentration (AUC0-t)
Measure:AUC0-∞ as a Pharmacokinetic (PK) assessments for CWP232291
Time Frame:3rd Cycle (each cycle = 28 days), Cycle 1 Day 1: Pre, 0.5hr, 1hr, 2hr, 3hr, 4hr, 5hr, 8hr, and 24hr after the start of infusion in Part A and at Cycle 1 Day 1: Pre, 2hr, 4hr, 8hr, and 24hr after the start of infusion in Part B.
Safety Issue:
Description:area under the time concentration curve from time zero to infinity (AUC0-∞)
Measure:AUC0-τ as a Pharmacokinetic (PK) assessments for CWP232291
Time Frame:3rd Cycle (each cycle = 28 days), Cycle 1 Day 1: Pre, 0.5hr, 1hr, 2hr, 3hr, 4hr, 5hr, 8hr, and 24hr after the start of infusion in Part A and at Cycle 1 Day 1: Pre, 2hr, 4hr, 8hr, and 24hr after the start of infusion in Part B.
Safety Issue:
Description:area under the time concentration curve from time zero the end of the dosage interval (AUC0-τ)
Measure:t½ as a Pharmacokinetic (PK) assessments for CWP232291
Time Frame:3rd Cycle (each cycle = 28 days), Cycle 1 Day 1: Pre, 0.5hr, 1hr, 2hr, 3hr, 4hr, 5hr, 8hr, and 24hr after the start of infusion in Part A and at Cycle 1 Day 1: Pre, 2hr, 4hr, 8hr, and 24hr after the start of infusion in Part B.
Safety Issue:
Description:terminal elimination half-life (t½)

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:JW Pharmaceutical

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