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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

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ClinicalTrials.gov Identifier: NCT02238925
Recruitment Status : Completed
First Posted : September 12, 2014
Results First Posted : November 30, 2017
Last Update Posted : November 30, 2017
Sponsor:
Information provided by (Responsible Party):
Jazz Pharmaceuticals

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Acute Myeloid Leukemia (AML)
Acute Lymphoblastic Leukemia (ALL)
Myelodysplastic Syndrome (MDS)
Intervention Drug: CPX-351
Enrollment 26
Recruitment Details  
Pre-assignment Details  
Arm/Group Title CPX-351
Hide Arm/Group Description

Single Arm Study (Patients may receive up to 2 Inductions and up to 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: CPX-351 will be given intravenously at 65units/m2 on days 1 and 3 over a 90 minute infusion.

CPX-351

Period Title: Overall Study
Started 26
Completed 1
Not Completed 25
Arm/Group Title CPX-351
Hide Arm/Group Description

Single Arm Study (Patients may receive up to 2 Inductions and up to 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: CPX-351 will be given intravenously at 65units/m2 on days 1 and 3 over a 90 minute infusion.

CPX-351

Overall Number of Baseline Participants 26
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 26 participants
65.2  (9.31)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants
Female
12
  46.2%
Male
14
  53.8%
1.Primary Outcome
Title Effect of CPX-351 on Cardiac Ventricular Repolarization (QTcF)
Hide Description Time-matched QTcF Changes From Baseline after the start of first infusion
Time Frame 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who received any dose of study drug and had at least 1 time-matched change from baseline in ECG parameters.
Arm/Group Title CPX-351
Hide Arm/Group Description:

Single Arm Study (Patients may receive up to 2 Inductions and up to 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: CPX-351 will be given intravenously at 65units/m2 on days 1 and 3 over a 90 minute infusion.

CPX-351

Overall Number of Participants Analyzed 26
Mean (Standard Deviation)
Unit of Measure: msecs
Time-point 0.75 h 0.6  (15.13)
Time-point 1.5 h -1.2  (13.30)
Time-point 2 h 4.3  (15.96)
Time-point 3 h 5.3  (15.17)
Time-point 4 h 8.0  (11.69)
Time-point 6 h -0.1  (11.24)
Time-point 8 h 4.8  (8.52)
Time-point 12 h -2.3  (10.43)
Time-point 24 h -6.2  (13.91)
2.Secondary Outcome
Title Serum Copper Levels Change From Baseline
Hide Description Change from Baseline to Induction 1, Day 5
Time Frame During 1st induction (up to 5 days)
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who received at least 1 dose of study drug and copper data were collected.
Arm/Group Title CPX-351
Hide Arm/Group Description:

Single Arm Study (Patients may receive up to 2 Inductions and up to 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: CPX-351 will be given intravenously at 65units/m2 on days 1 and 3 over a 90 minute infusion.

CPX-351

Overall Number of Participants Analyzed 24
Mean (Standard Deviation)
Unit of Measure: μg/dL
64.95  (51.119)
3.Secondary Outcome
Title Complete Response Rate
Hide Description [Not Specified]
Time Frame Following 1st induction, following 2nd induction if applicable
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy population: All subjects who received at least 1 dose of study drug.
Arm/Group Title CPX-351
Hide Arm/Group Description:

Single Arm Study (Patients may receive up to 2 Inductions and up to 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: CPX-351 will be given intravenously at 65units/m2 on days 1 and 3 over a 90 minute infusion.

CPX-351

Overall Number of Participants Analyzed 26
Measure Type: Count of Participants
Unit of Measure: Participants
8
  30.8%
4.Secondary Outcome
Title Tmax
Hide Description [Not Specified]
Time Frame Induction 1, Day 5
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title CPX-351
Hide Arm/Group Description:

Single Arm Study (Patients may receive up to 2 Inductions and up to 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: CPX-351 will be given intravenously at 65units/m2 on days 1 and 3 over a 90 minute infusion.

CPX-351

Overall Number of Participants Analyzed 26
Median (Full Range)
Unit of Measure: hours
Cytarabine
2.00
(0.75 to 8.33)
Ara-U
8.00
(5.78 to 8.33)
Daunorubicin
2.00
(0.75 to 6.02)
Daunorubicinol
26.00
(1.50 to 48.00)
5.Secondary Outcome
Title Cmax
Hide Description [Not Specified]
Time Frame Induction 1, Day 5
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title CPX-351
Hide Arm/Group Description:

Single Arm Study (Patients may receive up to 2 Inductions and up to 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: CPX-351 will be given intravenously at 65units/m2 on days 1 and 3 over a 90 minute infusion.

CPX-351

Overall Number of Participants Analyzed 26
Mean (Standard Deviation)
Unit of Measure: ng/ml
Cytarabine 62200  (20900)
Ara-U 1240  (252)
Daunorubicin 26000  (8510)
Daunorubicinol 147  (52.3)
Time Frame Adverse events were recorded from the start of infusion to the last day of the study period, whereas Serious Adverse Events were reported from the start of infusion until 30 days after completion of the study period.
Adverse Event Reporting Description The Safety population included subjects receiving at least 1 dose of study drug.
 
Arm/Group Title CPX-351
Hide Arm/Group Description

Single Arm Study (Patients may receive up to 2 Inductions and up to 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: CPX-351 will be given intravenously at 65units/m2 on days 1 and 3 over a 90 minute infusion.

CPX-351

All-Cause Mortality
CPX-351
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
CPX-351
Affected / at Risk (%)
Total   8/26 (30.77%) 
Blood and lymphatic system disorders   
Febrile Neutropenia  7/26 (26.92%) 
Gastrointestinal disorders   
Ileus  1/26 (3.85%) 
Infections and infestations   
Catheter Site Infection  1/26 (3.85%) 
Lung Infection  1/26 (3.85%) 
Meningitis Bacterial  1/26 (3.85%) 
Pathogen Resistance  1/26 (3.85%) 
Pneumonia  1/26 (3.85%) 
Pulmonary Mycosis  1/26 (3.85%) 
Sepsis  1/26 (3.85%) 
Investigations   
Ejection Fraction Decreased  1/26 (3.85%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Acute Myeloid Leukamia Recurrent  1/26 (3.85%) 
Respiratory, thoracic and mediastinal disorders   
Acute Respiratory Failure  1/26 (3.85%) 
Hypoxia  1/26 (3.85%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
CPX-351
Affected / at Risk (%)
Total   26/26 (100.00%) 
Blood and lymphatic system disorders   
Febrile Neutropenia  17/26 (65.38%) 
Cardiac disorders   
Sinus Tachycardia  5/26 (19.23%) 
Tachycardia  4/26 (15.38%) 
Eye disorders   
Blepharospasm  2/26 (7.69%) 
Conjunctival Haemorrhage  2/26 (7.69%) 
Dry Eye  2/26 (7.69%) 
Vitreous Floaters  2/26 (7.69%) 
Gastrointestinal disorders   
Nausea  14/26 (53.85%) 
Diarrhoea  12/26 (46.15%) 
Constipation  11/26 (42.31%) 
Vomiting  10/26 (38.46%) 
Abdominal Pain  6/26 (23.08%) 
Gingival Bleeding  4/26 (15.38%) 
Abdominal Pain Lower  3/26 (11.54%) 
Dysphagia  3/26 (11.54%) 
Faecal Incontinence  3/26 (11.54%) 
Stomatitis  3/26 (11.54%) 
Cheilitis  2/26 (7.69%) 
Gastrooesophageal Reflux Disease  2/26 (7.69%) 
Gingival Pain  2/26 (7.69%) 
Haemorrhoids  2/26 (7.69%) 
General disorders   
Fatigue  14/26 (53.85%) 
Oedema Peripheral  10/26 (38.46%) 
Chills  7/26 (26.92%) 
Pyrexia  6/26 (23.08%) 
Gait Disturbance  3/26 (11.54%) 
Mucosal Inflammation  3/26 (11.54%) 
Non-Cardiac Chest Pain  3/26 (11.54%) 
Nodule  2/26 (7.69%) 
Infections and infestations   
Bacteraemia  3/26 (11.54%) 
Sinusitis  3/26 (11.54%) 
Cellulitis  2/26 (7.69%) 
Clostridium Difficile Colitis  2/26 (7.69%) 
Device Related Infection  2/26 (7.69%) 
Folliculitis  2/26 (7.69%) 
Staphylococcal Bacteraemia  2/26 (7.69%) 
Injury, poisoning and procedural complications   
Contusion  3/26 (11.54%) 
Excoriation  2/26 (7.69%) 
Investigations   
Human Rhinovirus Test Positive  2/26 (7.69%) 
Viral Test Positive  2/26 (7.69%) 
Weight Decreased  2/26 (7.69%) 
Weight Increased  2/26 (7.69%) 
Metabolism and nutrition disorders   
Decreased Appetite  12/26 (46.15%) 
Fluid Overload  3/26 (11.54%) 
Fluid Retention  2/26 (7.69%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  6/26 (23.08%) 
Back Pain  6/26 (23.08%) 
Neck Pain  5/26 (19.23%) 
Muscular Weakness  3/26 (11.54%) 
Musculoskeletal Pain  3/26 (11.54%) 
Pain In Jaw  3/26 (11.54%) 
Joint Swelling  2/26 (7.69%) 
Musculoskeletal Chest Pain  2/26 (7.69%) 
Musculoskeletal Stiffness  2/26 (7.69%) 
Myalgia  2/26 (7.69%) 
Pain In Extremity  2/26 (7.69%) 
Nervous system disorders   
Headache  11/26 (42.31%) 
Dizziness  5/26 (19.23%) 
Dizziness Postural  3/26 (11.54%) 
Tremor  3/26 (11.54%) 
Ataxia  2/26 (7.69%) 
Hypoaesthesia  2/26 (7.69%) 
Sinus Headache  2/26 (7.69%) 
Psychiatric disorders   
Insomnia  11/26 (42.31%) 
Confusional State  6/26 (23.08%) 
Depression  4/26 (15.38%) 
Agitation  3/26 (11.54%) 
Anxiety  2/26 (7.69%) 
Delirium  2/26 (7.69%) 
Sleep Disorder  2/26 (7.69%) 
Renal and urinary disorders   
Chromaturia  4/26 (15.38%) 
Pollakiuria  4/26 (15.38%) 
Urinary Incontinence  4/26 (15.38%) 
Haematuria  3/26 (11.54%) 
Dysuria  2/26 (7.69%) 
Micturition Urgency  2/26 (7.69%) 
Urinary Retention  2/26 (7.69%) 
Respiratory, thoracic and mediastinal disorders   
Cough  9/26 (34.62%) 
Hypoxia  7/26 (26.92%) 
Oropharyngeal Pain  7/26 (26.92%) 
Epistaxis  6/26 (23.08%) 
Dyspnoea  5/26 (19.23%) 
Atelectasis  4/26 (15.38%) 
Pleural Effusion  4/26 (15.38%) 
Pulmonary Oedema  4/26 (15.38%) 
Dysphonia  3/26 (11.54%) 
Nasal Congestion  3/26 (11.54%) 
Rales  3/26 (11.54%) 
Wheezing  3/26 (11.54%) 
Haemoptysis  2/26 (7.69%) 
Pneumonitis  2/26 (7.69%) 
Productive Cough  2/26 (7.69%) 
Pulmonary Mass  2/26 (7.69%) 
Rhinorrhoea  2/26 (7.69%) 
Upper-Airway Cough Syndrome  2/26 (7.69%) 
Skin and subcutaneous tissue disorders   
Rash Maculo-Papular  5/26 (19.23%) 
Erythema  4/26 (15.38%) 
Petechiae  4/26 (15.38%) 
Pruritus  4/26 (15.38%) 
Rash  4/26 (15.38%) 
Hyperhidrosis  3/26 (11.54%) 
Rash Erythematous  3/26 (11.54%) 
Rash Papular  3/26 (11.54%) 
Rash Pruritic  3/26 (11.54%) 
Blood Blister  2/26 (7.69%) 
Erythema Multiforme  2/26 (7.69%) 
Purpura  2/26 (7.69%) 
Rash Macular  2/26 (7.69%) 
Skin Mass  2/26 (7.69%) 
Vascular disorders   
Hypotension  8/26 (30.77%) 
Hypertension  4/26 (15.38%) 
Flushing  2/26 (7.69%) 
Haematoma  2/26 (7.69%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Associate Director, Clinical Trial Disclosure & Transparency
Organization: Jazz Pharmaceuticals
EMail: tom.chmielewski@jazzpharma.com
Layout table for additonal information
Responsible Party: Jazz Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02238925     History of Changes
Other Study ID Numbers: CLTR0310-206
First Submitted: August 14, 2014
First Posted: September 12, 2014
Results First Submitted: September 3, 2017
Results First Posted: November 30, 2017
Last Update Posted: November 30, 2017