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

NCT04038437 | Completed Phase 1 FDA Drug

• 1 other identifier: CPX351-103
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 8

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) and to determine the recommended phase 2 dose (RP2D) for the Expansion Phase. This study will comprise 2 phases: a Dose Exploration Phase (Part 1) and an Expansion Phase (Part 2), in which all subjects will receive a combination of CPX-351 and venetoclax.

Conditions

Acute Myeloid Leukemia

Keywords

CPX-351; Vyxeos; Venetoclax; Unfit

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) as determined by the specified dose exploration

  The Recommended Phase 2 Dose (RP2D) as determined by an assessment of all safety data from the Dose Exploration Phase.

  Up to 36 months

• Incidence of Adverse Events (AE) and Dose Limiting Toxicities (DLT)

  The safety and tolerability of CPX-351 and venetoclax when given in combination based on the incidence of AEs and DLTs

  Up to 36 months

Secondary Outcomes (7)

• Proportion of subjects who have achieved CR, CRi, PR, and CRc (CR + CRi)

  Up to 36 months

• Proportion of subjects who have achieved ORR

  Up to 36 months

• Proportion of subjects who have achieved CR / CRi with MRD status

  Up to 36 months

• AUCtau

  Exploration: Cycle 1, Days 1 and 3: predose, 45 and 90 minutes (min), 4, 6, and 8 hours(hr); Days 2 and 4: 24 hr; Day 5: 48 hr; Cycle 2 Day 3: predose, 45 and 90 min, 4, 5, 6, and 8 hr; Day 4: 24 hr; Day 5: 48 hr (each cycle is 28-49 days)

• Maximum Plasma Concentration (Cmax)

  Exploration:Cycle 1,Days 1 and 3:predose,45 and 90 minutes(min),4,6, and 8 hours (hr); Days 2 and 4:24 hr; Day 5:48 hr; Day 7:96 hr, Day 9:144 hr; Cycle 2 Day 3:predose,45 and 90 min,4,5,6, and 8 hr; Day 4:24 hr; Day 5:48 hr (each cycle is 28-49 days)

Study Arms (1)

CPX-351 and Venetoclax

EXPERIMENTAL

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

Drug: CPX-351; Drug: Venetoclax

Interventions

CPX-351 DRUG

CPX-351 will be administered on Days 1 and 3 of each cycle

Also known as: Vyxeos

CPX-351 and Venetoclax

Venetoclax DRUG

Venetoclax will be adminstered on Days 2 to 21 of each cycle

Also known as: Venclexta

CPX-351 and Venetoclax

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (8)

City of Hope

Duarte, California, 91010, United States

Location

Blood & Marrow Transplant Group of Georgia

Atlanta, Georgia, 30342, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Dana Farber/ Brigham & Women's Cancer Center

Boston, Massachusetts, 02215, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

MUSC Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Uy GL, Pullarkat V, Baratam P, Stuart RK, Walter RB, Winer ES, Wang Q, Faderl S, Chakravarthy D, Menno D, Cheung RS, Lin TL. Lower-intensity CPX-351 plus venetoclax induction for adults with newly diagnosed AML unfit for intensive chemotherapy. Blood Adv. 2024 Dec 24;8(24):6248-6256. doi: 10.1182/bloodadvances.2024013687.

  PMID: 39418644 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

CPX-351; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2019
• First Posted: July 30, 2019
• Study Start: October 15, 2019
• Primary Completion: April 26, 2022
• Study Completion: September 24, 2022
• Last Updated: November 9, 2022

Record last verified: 2022-11

Locations

US (8)