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Acute Myeloid LeukemiaPhase 1NCT04038437

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

A Phase 1 study testing CPX-351 and Venetoclax in people with Acute Myeloid Leukemia, run by Jazz Pharmaceuticals at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
CPX-351 and Venetoclax
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
8 sitesUnited States
Study dates
15 Oct 2019to 24 Sep 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
Show all 31Show fewer
  • 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 28 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 × 10^9/L. (Note: subjects who have undergone hydroxyurea administration or leukapheresis for therapeutic cytoreduction will be considered eligible).

Who cannot join

  • 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.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Blood & Marrow Transplant Group of Georgia

    Atlanta, Georgia, 30342

  • Dana Farber/ Brigham & Women's Cancer Center

    Boston, Massachusetts, 02215

  • MUSC Hollings Cancer Center

    Charleston, South Carolina, 29425

  • City of Hope

    Duarte, California, 91010

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

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

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.

Being tested
CPX-351, Venetoclax
Keywords
CPX-351, Vyxeos, Venetoclax, Unfit
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CPX-351Drug

    Also called Vyxeos

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

  • VenetoclaxDrug

    Also called Venclexta

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

Study groups in NCT04038437
Study groupRoleWhat they receive
CPX-351 and VenetoclaxExperimentalCPX-351 and Venetoclax will be administered over 28 day cycles
Receives: Drug: CPX-351; Drug: Venetoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 36 months

  2. 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

    Measured: Up to 36 months

Secondary outcomes (7)

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

    Proportion of subjects who have achieved CR, CRi, PR, and CRc (CR + CRi) at any time while receiving study treatment.

    Measured: Up to 36 months

  2. Proportion of subjects who have achieved ORR

    Proportion of subjects who have achieved ORR, defined as best response (CR + CRi + PR) at any time while receiving study treatment.

    Measured: Up to 36 months

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

    Proportion of subjects who have achieved CR / CRi with MRD status (negative / positive) at any time while receiving study treatment.

    Measured: Up to 36 months

  4. AUCtau

    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

    Measured: 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)

  5. Maximum Plasma Concentration (Cmax)

    Measured: 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)

  6. Time to Cmax (Tmax)

    Measured: 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)

  7. Apparent Terminal Elimination Half-Life (t½)

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jul 2019
  2. Study start15 Oct 2019
  3. Primary completion26 Apr 2022
  4. Study completion24 Sep 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04038437
Sponsor's protocol ID
CPX351-103
Status last verified
Nov 2022
First submitted
26 Jul 2019
Last updated
9 Nov 2022
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 39418644

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CPX-351 and Venetoclax in people with Acute Myeloid Leukemia, run by Jazz Pharmaceuticals at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 31 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) as determined by the specified dose exploration (time frame: Up to 36 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04038437, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Nov 2022.

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