Clinical Trials /

A Trial of CPX-351 Lower Intensity Therapy (LIT) Plus Venetoclax as First Line Treatment for Subjects With AML

NCT04038437

Description:

Study CPX351-103 is an open-label, multicenter, phase 1b, safety and PK study to determine the MTD of the combination of CPX 351 and venetoclax when administered to subjects with newly diagnosed AML who are unfit for intensive chemotherapy (ICT). This study will comprise 2 phases: a Dose Escalation Phase and an Expansion Phase, in which all subjects will receive a combination of CPX-351 and venetoclax.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Trial of CPX-351 Lower Intensity Therapy (LIT) Plus Venetoclax as First Line Treatment for Subjects With AML
  • Official Title: A Phase 1b Trial of CPX-351 Lower Intensity Therapy (LIT) Plus Venetoclax as First Line Treatment for Subjects With AML Who Are Unfit for Intensive Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: CPX351-103
  • NCT ID: NCT04038437

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
CPX-351VyxeosCPX-351 and Venetoclax
VenetoclaxVenclextaCPX-351 and Venetoclax

Purpose

Study CPX351-103 is an open-label, multicenter, phase 1b, safety and PK study to determine the MTD of the combination of CPX 351 and venetoclax when administered to subjects with newly diagnosed AML who are unfit for intensive chemotherapy (ICT). This study will comprise 2 phases: a Dose Escalation Phase and an Expansion Phase, in which all subjects will receive a combination of CPX-351 and venetoclax.

Trial Arms

NameTypeDescriptionInterventions
CPX-351 and VenetoclaxExperimentalCPX-351 and Venetoclax will be administered over 28 day cycles
  • CPX-351
  • Venetoclax

Eligibility Criteria

        Inclusion Criteria:

        • Subject must have newly diagnosed AML with histological confirmation by World Health
        Organization (WHO) criteria.

        Definition of subjects who are unfit for ICT:

        • Each subject must meet the following criteria characterizing him / her as unfit to
        receive ICT within 21 days prior to the first day of therapy to be enrolled in the study:

          -  ≥ 75 years of age OR

          -  ≥ 18 to 74 years of age and fulfilling at least 1 criteria associated with lack of
             fitness for ICT as follows:

               -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 to 3;

               -  Cardiac history of Congestive Heart Failure (CHF) requiring treatment or left
                  ventricular ejection fraction (LVEF) ≤ 50%.

               -  Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) ≤ 65% or Forced
                  Expiratory Volume in 1 second (FEV1) ≤ 65%;

               -  Creatinine clearance (CrCl) ≥ 30 mL/min to < 45 mL/min calculated by the
                  Cockcroft-Gault formula;

               -  Moderate hepatic impairment with total bilirubin > 1.5 to ≤ 3.0 × Upper Limit of
                  Normal (ULN);

               -  Other comorbidity that the physician judges to be incompatible with conventional
                  intensive chemotherapy which must be reviewed and approved by the study medical
                  monitor before study enrollment.

        In addition, all subjects must meet the following criteria:

          -  If the subject is ≥ 75 years of age, then ECOG Performance Status must be 0-2.

          -  Subject must have adequate renal function as demonstrated by a CrCl ≥ 30 mL/min
             (calculated by the Cockcroft Gault formula or measured by 24-hour urine collection).

          -  Subject must have adequate liver function as demonstrated by:

               -  Aspartate aminotransferase (AST) ≤ 3.0 × ULN*

               -  Alanine aminotransferase (ALT) ≤ 3.0 × ULN*

               -  Bilirubin ≤ 1.5 × ULN (subjects who are < 75 years of age may have bilirubin of ≤
                  3.0 × ULN)* *Unless considered to be due to leukemic organ involvement.

          -  Female subjects must be either postmenopausal defined as:

               -  Age > 55 years with no menses for ≥ 2 years without an alternative medical cause.

               -  OR

               -  Age ≤ 55 years with no menses for ≥ 12 months without an alternative medical
                  cause AND a follicle-stimulating hormone level > 40 IU/L;

               -  OR

               -  Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or
                  hysterectomy); OR

          -  A woman of childbearing potential practicing at least 1 protocol specified method of
             birth control starting at Study Day 1 through at least 6 months after the last dose of
             study treatment.

          -  A woman of childbearing potential must have negative results for pregnancy test
             performed:

               -  At Pretreatment with a serum sample obtained within 14 days prior to the first
                  study treatment administration, and

               -  Prior to dosing with urine sample obtained on Cycle 1 Day 1, if it has been > 7
                  days since obtaining the serum pregnancy test results.

               -  Subjects with borderline pregnancy tests at Pretreatment must have a serum
                  pregnancy test ≥ 3 days later to document continued lack of a positive result.

          -  Male subjects who are sexually active, must agree, from Study Day 1 through at least 6
             months after the last dose of study treatment, to practice protocol specified methods
             of contraception. Male subjects must agree to refrain from sperm donation from initial
             study treatment administration through at least 6 months after the last dose of study
             treatment.

          -  Subject must have a white blood cell count ≤ 25 × 109/L. (Note: subjects who have
             undergone hydroxyurea administration or leukapheresis for therapeutic cytoreduction
             will be considered eligible).

        Exclusion Criteria:

          -  Subject has ECOG Performance Status > 3, regardless of age.

          -  Subject has known Human Immunodeficiency Virus (HIV) infection (due to potential
             drug-drug interactions between antiretroviral medications and venetoclax). HIV testing
             will be performed at Pretreatment, if required per local guidelines or institutional
             standards.

          -  Subject has consumed grapefruit, grapefruit products, Seville oranges (including
             marmalade containing Seville oranges) or Star fruit within 3 days prior to the
             initiation of study treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD) as determined by the specified dose escalation
Time Frame:Up to 30 months
Safety Issue:
Description:The MTD as determined by the specified dose escalation and MTD algorithm

Secondary Outcome Measures

Measure:Proportion of subjects who have achieved CR, CRi, PR, and CRc (CR + CRi)
Time Frame:Up to 30 months
Safety Issue:
Description:Proportion of subjects who have achieved CR, CRi, PR, and CRc (CR + CRi) by the completion of treatment (up to 4 cycles of therapy)
Measure:Proportion of subjects who have achieved ORR
Time Frame:Up to 30 months
Safety Issue:
Description:Proportion of subjects who have achieved ORR, defined as best response (CR + CRi + PR) by the completion of treatment (up to 4 cycles of therapy)
Measure:Proportion of subjects who have achieved CR / CRi with MRD status
Time Frame:Up to 30 months
Safety Issue:
Description:Proportion of subjects who have achieved CR / CRi with MRD status (negative / positive) by the completion of treatment (up to 4 cycles of therapy)
Measure:AUCtau
Time Frame:Up to 30 months
Safety Issue:
Description:Area under the plasma concentration time curve from time 0 to the time of the next dosing during a 48 hour interval at the steady-state of CPX-351 PK
Measure:Maximum Plasma Concentration (Cmax)
Time Frame:Up to 30 months
Safety Issue:
Description:
Measure:Time to Cmax (Tmax)
Time Frame:Up to 30 months
Safety Issue:
Description:
Measure:Apparent Terminal Elimination Half-Life (t½)
Time Frame:Up to 30 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Jazz Pharmaceuticals

Trial Keywords

  • CPX-351
  • Vyxeos
  • Venetoclax
  • Unfit

Last Updated

November 1, 2019