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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04038437
Recruitment Status : Recruiting
First Posted : July 30, 2019
Last Update Posted : November 5, 2019
Sponsor:
Information provided by (Responsible Party):
Jazz Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE July 26, 2019
First Posted Date  ICMJE July 30, 2019
Last Update Posted Date November 5, 2019
Actual Study Start Date  ICMJE October 15, 2019
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 29, 2019)
  • Maximum Tolerated Dose (MTD) as determined by the specified dose escalation [ Time Frame: Up to 30 months ]
    The MTD as determined by the specified dose escalation and MTD algorithm
  • Incidence of Adverse Events (AE) and Dose Limiting Toxicities (DLT) [ Time Frame: Up to 30 months ]
    The safety and tolerability of CPX-351 and venetoclax when given in combination based on the incidence of AEs and DLTs
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 29, 2019)
  • Proportion of subjects who have achieved CR, CRi, PR, and CRc (CR + CRi) [ Time Frame: Up to 30 months ]
    Proportion of subjects who have achieved CR, CRi, PR, and CRc (CR + CRi) by the completion of treatment (up to 4 cycles of therapy)
  • Proportion of subjects who have achieved ORR [ Time Frame: Up to 30 months ]
    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)
  • Proportion of subjects who have achieved CR / CRi with MRD status [ Time Frame: Up to 30 months ]
    Proportion of subjects who have achieved CR / CRi with MRD status (negative / positive) by the completion of treatment (up to 4 cycles of therapy)
  • AUCtau [ Time Frame: Up to 30 months ]
    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
  • Maximum Plasma Concentration (Cmax) [ Time Frame: Up to 30 months ]
  • Time to Cmax (Tmax) [ Time Frame: Up to 30 months ]
  • Apparent Terminal Elimination Half-Life (t½) [ Time Frame: Up to 30 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Trial of CPX-351 Lower Intensity Therapy (LIT) Plus Venetoclax as First Line Treatment for Subjects With AML
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukemia
Intervention  ICMJE
  • Drug: CPX-351
    CPX-351 will be administered on Days 1 and 3 of each cycle
    Other Name: Vyxeos
  • Drug: Venetoclax
    Venetoclax will be adminstered on Days 2 to 21 of each cycle
    Other Name: Venclexta
Study Arms  ICMJE Experimental: CPX-351 and Venetoclax
CPX-351 and Venetoclax will be administered over 28 day cycles
Interventions:
  • Drug: CPX-351
  • Drug: Venetoclax
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 29, 2019)
44
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2022
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Director Clinical Trial Disclosure & Transparency 2159707145 ClinicalTrialDisclosure@JazzPharma.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04038437
Other Study ID Numbers  ICMJE CPX351-103
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jazz Pharmaceuticals
Study Sponsor  ICMJE Jazz Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Jazz Pharmaceuticals
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP