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

NCT02238925 | Completed Phase 2 Results

• 1 other identifier: CLTR0310-206
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Acute Myeloid Leukemia (AML); Acute Lymphoblastic Leukemia (ALL); Myelodysplastic Syndrome (MDS)

Keywords

Newly Diagnosed AML; Secondary AML; Relapsed/Refractory AML; Relapsed/Refractory ALL; MDS

Outcome Measures

Primary Outcomes (1)

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

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

  21 days

Secondary Outcomes (4)

• Serum Copper Levels Change From Baseline

  During 1st induction (up to 5 days)

• Complete Response Rate

  Following 1st induction, following 2nd induction if applicable

• Tmax

  Induction 1, Day 5

• Cmax

  Induction 1, Day 5

Study Arms (1)

CPX-351

EXPERIMENTAL

Single 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.

Drug: CPX-351

Interventions

CPX-351 DRUG

CPX-351

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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)
• 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

You may not qualify if:

• 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)
• 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
• 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.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (5)

Franciscan Saint Francis Health

Indianapolis, Indiana, 46237, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• 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.

  PMID: 31098682 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Recurrence

Interventions

CPX-351

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Associate Director, Clinical Trial Disclosure & Transparency
• Organization: Jazz Pharmaceuticals

tom.chmielewski@jazzpharma.com

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2014
• First Posted: September 12, 2014
• Study Start: July 1, 2014
• Primary Completion: May 1, 2015
• Study Completion: January 1, 2016
• Last Updated: November 30, 2017
• Results First Posted: November 30, 2017

Record last verified: 2017-10

Locations

US (5)