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Acute Myeloid Leukemia (AML)Phase 2NCT02238925

An Open Label Phase II Pharmacokinetic and Pharmacodynamic Assessment of the Potential for QTc Prolongation Following First Induction Treatment With CPX-351 (Cytarabine:Daunorubicin) Liposome Injection in Acute Leukemias and MDS Patients

A Phase 2 study testing CPX-351 in people with Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL), run by Jazz Pharmaceuticals at 5 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

The purpose of this study is to assess the effects of CPX-351 on cardiac repolarization, assess plasma drug levels, asses serum copper levels, and assess drug levels in urine. Efficacy and Safety will be assessed in all patients enrolled to the study. Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
CPX-351
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
5 sitesUnited States
Study dates
Jul 2014to Jan 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Ability to understand and voluntarily sign an informed consent form
  • Age ≥ 18 to ≤ 80 years at the time of signing the informed consent form
  • Life expectancy of at least 3 months
  • Pathological confirmation by bone marrow documenting the following:
  • Newly Diagnosed De novo AML according to WHO criteria except for Acute Promyelocytic Leukemia or patients with known favorable cytogenetics (see exclusion)
  • Newly Diagnosed Secondary AML age <60 years and ≥76 to 80 years, defined as having a history of an antecedent hematologic disorder (myelodysplastic syndromes [MDS], myeloproliferative disease [MPD]or history of cytotoxic treatment for non-hematologic malignancy)
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  • Patients with relapsed/refractory AML regardless of cytogenetic risk
  • Patients with relapsed/refractory ALL
  • Patients with MDS (IPSS score ≥ 1.5)
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2
  • Able to adhere to the study visit schedule and other protocol requirements
  • Laboratory values fulfilling the following:
  • Serum Creatinine ≤ 2.0mg/dL
  • Hepatic function with a score of < 7 points according to the Child-Pugh System
  • Serum alanine aminotransferase or aspartate aminotransferase < 3 times the ULN. Note: If elevated liver enzymes are related to disease; contact medical monitor to discuss.
  • Cardiac ejection fraction ≥50% by ECHO or MUGA
  • Screening and Baseline QTcF (Fridericia's) less than 470 msec
  • Patients with second malignancies in remission may be eligible if there is clinical evidence of disease stability for a period of greater than 6 months off cytotoxic chemotherapy, documented by imaging, tumor marker studies, etc., at screening. Patients maintained on long-term non-chemotherapy treatment, e.g., hormonal therapy, are eligible.
  • All men and women must agree to practice effective contraception during the study period if not otherwise documented to be infertile.

Who cannot join

  • Patients eligible for participation in Study CLTR0310-301 (Phase III study of CPX-351 NCT01696084) or who have already participated in that study are not eligible for this study.
  • Patients taking medications known to prolong the QTc interval directly or that interact pharmacodynamically with medicines to prolong the QTc interval.
  • Rhythm abnormalities (other than sinus bradycardia with HR < 50 bpm)
  • AV block (other than 1o AV Block with PR > 200 msec)
  • Bundle branch block or QRS ≥ 120 msec
  • Abnormal T wave morphology (other than slight flattening)
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  • Pathological U waves
  • Other QRS or T/U morphology preventing accurate determination of QT interval
  • Patients with unexplained syncope, history of or known risk factors for torsade des pointes, including congenital long QT syndrome, or family history of LQTS.
  • Patients with history of and/or current evidence of myocardial impairment (e.g. cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, and congestive heart failure) resulting in heart failure by New York Heart Association Criteria (Class III or IV staging)
  • Newly diagnosed patients with Acute promyelocytic leukemia [t(15;17)] or favorable cytogenetics, including t(8;21) or inv16
  • Clinical evidence of active CNS leukemic involvement
  • Chemotherapy or other investigational anticancer therapeutic drugs within 1 week prior to study entry unless AEs have resolved and there is no interference with the assessment of efficacy or safety; in the event of rapidly proliferative disease, however, the use of hydroxyurea is permitted up to 12 hours before study entry. Patients with prior bone marrow or stem cell transplant, considered for inclusion, should be discussed with the medical monitor first.
  • Any serious medical condition or psychiatric illness that would prevent the patient from providing informed consent
  • Patients with prior cumulative anthracycline exposure of greater than 368 mg/m2 daunorubicin (or equivalent)
  • Active or uncontrolled infection. Patients with any infection receiving treatment (antibiotic, antifungal or antiviral treatment) may be entered into the study but must be afebrile and hemodynamically stable for ≥72 hrs. Patients with fevers believed to be due to leukemia or MDS are eligible provided a thorough infection work-up is negative and the patient is clinically and hemodynamically stable.
  • Pregnant or lactating women
  • Hypersensitivity to cytarabine, daunorubicin or liposomal products
  • History of Wilson's disease or other copper-related metabolic disorder

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Franciscan Saint Francis Health

    Indianapolis, Indiana, 46237

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • University of Kansas Cancer Center

    Westwood, Kansas, 66205

Other trials in United States

About this study

The purpose of this study is to assess the effects of CPX-351 on cardiac repolarization, assess plasma drug levels, asses serum copper levels, and assess drug levels in urine.

Efficacy and Safety will be assessed in all patients enrolled to the study.

Read the detailed description

This study is an open-label, single-arm, Phase II, PK and pharmacodynamic (PD) trial of CPX-351 in patients with documented acute leukemia (AML or ALL) or MDS (IPSS score ≥ 1.5) and suitable for treatment with intensive chemotherapy. Each patient will be screened for hepatic impairment. Hepatic impairment will be assessed using the Child-Pugh system and only patients with a Child-Pugh score <7 points will be eligible for this study. Patients will receive up to two inductions and four consolidation courses. Patients will be monitored for safety (early deaths, adverse events, metabolic changes, etc.) and efficacy (response for AML, ALL, and MDS) while on the study.

Being tested
CPX-351
Keywords
Newly Diagnosed AML, Secondary AML, Relapsed/Refractory AML, Relapsed/Refractory ALL, MDS
Medical subject headings
Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Myelodysplastic Syndromes, Recurrence

What participants receive

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

  • CPX-351Drug

Study groups in NCT02238925
Study groupRoleWhat they receive
CPX-351ExperimentalSingle Arm Study (Patients may receive up to 2 Inductions and 4 Consolidations): Induction 1: CPX-351 will be given intravenously at 100units/m2 on days 1, 3, and 5 over a 90 minute infusion. Induction 2: CPX-351 will be given intravenously at 100units/m2 on days 1 and 3 over a 90 minute infusion. Consolidations 1-4: CPX-351 will be given intravenously at 65units/m2 on days 1 and 3 over a 90 minute infusion.
Receives: Drug: CPX-351

What is being measured

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

  1. Effect of CPX-351 on Cardiac Ventricular Repolarization (QTcF)

    Time-matched QTcF Changes From Baseline after the start of first infusion

    Measured: 21 days

Secondary outcomes (4)

  1. Serum Copper Levels Change From Baseline

    Change from Baseline to Induction 1, Day 5

    Measured: During 1st induction (up to 5 days)

  2. Complete Response Rate

    Measured: Following 1st induction, following 2nd induction if applicable

  3. Tmax

    Measured: Induction 1, Day 5

  4. Cmax

    Measured: Induction 1, Day 5

Timeline

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

  1. First posted12 Sep 2014 (estimated)
  2. Study startJul 2014
  3. Primary completionMay 2015
  4. Study completionJan 2016

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02238925
Sponsor's protocol ID
CLTR0310-206
Status last verified
Oct 2017
First submitted
14 Aug 2014
Last updated
30 Nov 2017
Data monitoring committee
No

Publications

  • Lin TL, Newell LF, Stuart RK, Michaelis LC, Rubenstein E, Pentikis HS, Callahan T, Alvarez D, Liboiron BD, Mayer LD, Wang Q, Banerjee K, Louie AC. A phase 2 study to assess the pharmacokinetics and pharmacodynamics of CPX-351 and its effects on cardiac repolarization in patients with acute leukemias. Cancer Chemother Pharmacol. 2019 Jul;84(1):163-173. doi: 10.1007/s00280-019-03856-9. Epub 2019 May 16.

    PubMed 31098682

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CPX-351 in people with Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL), run by Jazz Pharmaceuticals at 5 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 19 inclusion and 19 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 30 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Nov 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Effect of CPX-351 on Cardiac Ventricular Repolarization (QTcF) (time frame: 21 days). 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 NCT02238925, 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 30 Nov 2017.

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