Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 66 of 325 for:    "Acute Lymphocytic Leukemia" | "Methotrexate"

EZN-3042 Administered With Re-induction Chemotherapy in Children With Relapsed Acute Lymphoblastic Leukemia (ALL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01186328
Recruitment Status : Terminated (Enzon Pharmaceuticals decided to end its development of EZN-3042.)
First Posted : August 23, 2010
Results First Posted : July 24, 2019
Last Update Posted : July 24, 2019
Sponsor:
Collaborator:
Enzon Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Therapeutic Advances in Childhood Leukemia Consortium

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Lymphoblastic Leukemia, Acute
Lymphoblastic Leukemia, Acute, Childhood
Leukemia, Lymphoblastic, Acute, T Cell
Leukemia, Lymphoblastic, Acute
Interventions Drug: EZN-3042
Drug: Cytarabine
Drug: Doxorubicin
Drug: Prednisone
Drug: Vincristine
Drug: PEG-asparaginase
Drug: Methotrexate
Drug: Hydrocortisone
Enrollment 6
Recruitment Details 3 patients were initially enrolled onto Dose Level 1. 1 of 3 patients were found to experience a dose limiting toxicity. 3 additional patients were enrolled onto dose level 1. Another 1 patient was found to experience a DLT that was deemed possibly related to study medication EZN-3042. Study dose was deescalated to dose level 0.
Pre-assignment Details  
Arm/Group Title EZN Dose Level 1 EZN Dose Level 2 EZN Dose Level 3
Hide Arm/Group Description Dose Level 1 is the starting dose level. Patients will receive 2 doses of EZN-3042 at 2.5 mg/m2/day (and intrathecal cytarabine, conditionally) prior to initiating systemic therapy with vincristine, doxorubicin, prednisone and PEG-asparaginase, and then Day 8, 15, 22, and 29. If MTD is exceeded at dose level 1, the dose level will be deescalated to Dose Level 0. If the MTD is not exceeded at dose level 1, the dose will be escalated to dose level 2 at 5mg/m2/day. Dose will be administered following the same dosing schedule as Dose level 1. If the MTD is not exceeded at Dose Level 2, the dose will be escalated to Dose Level 3 at 6.5 mg/kg following the same dosing schedule as Dose Level 1 and 2.
Period Title: Overall Study
Started 6 0 0
Completed 5 0 0
Not Completed 1 0 0
Reason Not Completed
Death             1             0             0
Arm/Group Title EZN Dose Level 1
Hide Arm/Group Description Dose Level 1 is the starting dose level. Patients will receive 2 doses of EZN-3042 at 2.5 mg/m2/day (and intrathecal cytarabine, conditionally) prior to initiating systemic therapy with vincristine, doxorubicin, prednisone and PEG-asparaginase, and then Day 8, 15, 22, and 29. If MTD is exceeded at dose level 1, the dose level will be deescalated to Dose Level 0.
Overall Number of Baseline Participants 6
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants
<=18 years
5
  83.3%
Between 18 and 65 years
1
  16.7%
>=65 years
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants
Female
2
  33.3%
Male
4
  66.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants
Hispanic or Latino
3
  50.0%
Not Hispanic or Latino
2
  33.3%
Unknown or Not Reported
1
  16.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
1
  16.7%
White
5
  83.3%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Prior HSCT  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants
Yes
2
  33.3%
No
4
  66.7%
1.Primary Outcome
Title Maximum Tolerated Dose of EZN-3042
Hide Description To determine the recommended dose of EZN-3042 administered weekly in combination with re-induction chemotherapy. Based on disease response at Day 36 and toxicity profile assessed until 30 days after discontinuation of study drug.
Time Frame 2 months
Hide Outcome Measure Data
Hide Analysis Population Description
6 patients were enrolled at Dose Level 1. Dose level deescalated to Dose level 0 after 2 patients in Dose Level 1 experienced dose limiting toxicities. No patients were accrued on Dose level 0 prior to study closure.
Arm/Group Title EZN Dose Level 1 EZN Dose Level 0
Hide Arm/Group Description:
Dose Level 1 is the starting dose level. Patients will receive 2 doses of EZN-3042 at 2.5 mg/m2/day (and intrathecal cytarabine, conditionally) prior to initiating systemic therapy with vincristine, doxorubicin, prednisone and PEG-asparaginase, and then Day 8, 15, 22, and 29. If MTD is exceeded at dose level 1, the dose level will be deescalated to Dose Level 0.
Study deescalated to Dose Level 0 at 1.5 mg/kg after 2 patients at Dose Level 1 experienced DLTs.
Overall Number of Participants Analyzed 6 0
Measure Type: Count of Participants
Unit of Measure: Participants
Completed therapy w/o DLT
4
  66.7%
0
Experienced DLT
2
  33.3%
0
2.Secondary Outcome
Title Disease Response
Hide Description

Possible outcomes are:

Complete Remission (CR) defined as M1 bone marrow with no evidence of circulating blasts and with recovery of peripheral counts (ANC > 750 ul and PLT count > 75,000 uL) Complete Remission without Platelet Recovery (CRp) defined as attainment o M1 bone marrow with ANC > 750 uL, but with insufficient recovery of platelets (< 75,000 uL) Partial Remission (PR) defined as complete disappearance of circulating blasts and achievement of M2 marrow, without new sites of extramedullary disease and ANC > 750/uL) Stable Disease (SD) defined as recovery of ANC >750/uL but fails to qualify for CR, CRp, or PR Progressive Disease (PD) defined as an increase of at least 25% in absolute number of circulating leukemic cells, development of new sites of extramedullary disease, or other evidence of PD Induction Death defined as any patient who dies prior to receiving subsequent therapy

Time Frame Day 36
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title EZN Dose Level 1
Hide Arm/Group Description:
Dose Level 1 is the starting dose level. Patients will receive 2 doses of EZN-3042 at 2.5 mg/m2/day (and intrathecal cytarabine, conditionally) prior to initiating systemic therapy with vincristine, doxorubicin, prednisone and PEG-asparaginase, and then Day 8, 15, 22, and 29. If MTD is exceeded at dose level 1, the dose level will be deescalated to Dose Level 0.
Overall Number of Participants Analyzed 6
Measure Type: Count of Participants
Unit of Measure: Participants
CR
1
  16.7%
CRp
1
  16.7%
PR
0
   0.0%
SD
1
  16.7%
PD
2
  33.3%
Induction Death
1
  16.7%
Time Frame 11 months
Adverse Event Reporting Description The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
 
Arm/Group Title EZN Dose Level 1
Hide Arm/Group Description Dose Level 1 is the starting dose level. Patients will receive 2 doses of EZN-3042 at 2.5 mg/m2/day (and intrathecal cytarabine, conditionally) prior to initiating systemic therapy with vincristine, doxorubicin, prednisone and PEG-asparaginase, and then Day 8, 15, 22, and 29. If MTD is exceeded at dose level 1, the dose level will be deescalated to Dose Level 0.
All-Cause Mortality
EZN Dose Level 1
Affected / at Risk (%)
Total   4/6 (66.67%) 
Show Serious Adverse Events Hide Serious Adverse Events
EZN Dose Level 1
Affected / at Risk (%)
Total   3/6 (50.00%) 
Gastrointestinal disorders   
Gastric hemorrhage  1  1/6 (16.67%) 
Pancreatitis  1  1/6 (16.67%) 
Infections and infestations   
Lung infection  1  1/6 (16.67%) 
Enterocolitis infectious  1  1/6 (16.67%) 
Sepsis  1  1/6 (16.67%) 
Investigations   
Aspartate aminotransferase increased  1  1/6 (16.67%) 
GGT increased  1  1/6 (16.67%) 
Metabolism and nutrition disorders   
Hyperglycemia  1  1/6 (16.67%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
EZN Dose Level 1
Affected / at Risk (%)
Total   6/6 (100.00%) 
Blood and lymphatic system disorders   
Febrile neutropenia  1  1/6 (16.67%) 
Leukocytosis  1  1/6 (16.67%) 
Lymphocyte count decreased  1  3/6 (50.00%) 
Neutrophil count decreased  1  4/6 (66.67%) 
Platelet count decreased  1  6/6 (100.00%) 
White blood cell decreased  1  5/6 (83.33%) 
Cardiac disorders   
Pericardial effusion  1  1/6 (16.67%) 
Sinus tachycardia  1  2/6 (33.33%) 
Supraventricular tachycardia  1  1/6 (16.67%) 
Ear and labyrinth disorders   
Ear pain  1  1/6 (16.67%) 
Gastrointestinal disorders   
Abdominal pain  1  2/6 (33.33%) 
Diarrhea  1  1/6 (16.67%) 
Gastrointestinal disorders - Other, specify  1 [1]  1/6 (16.67%) 
Mucositis oral  1  5/6 (83.33%) 
Nausea  1  3/6 (50.00%) 
Oral pain  1  1/6 (16.67%) 
Vomiting  1  3/6 (50.00%) 
General disorders   
Fatigue  1  2/6 (33.33%) 
Fever  1  3/6 (50.00%) 
Infusion site extravasation  1  1/6 (16.67%) 
Pain  1  3/6 (50.00%) 
Hepatobiliary disorders   
Hepatobiliary disorders - Other, specify  1 [2]  1/6 (16.67%) 
Infections and infestations   
Enterocolitis infectious  1  1/6 (16.67%) 
Injury, poisoning and procedural complications   
Bruising  1  1/6 (16.67%) 
Investigations   
Activated partial thromboplastin time prolonged  1  1/6 (16.67%) 
Alanine aminotransferase increased  1  5/6 (83.33%) 
Alkaline phosphatase increased  1  2/6 (33.33%) 
Aspartate aminotransferase increased  1  3/6 (50.00%) 
Blood bilirubin increased  1  2/6 (33.33%) 
Electrocardiogram QT corrected interval prolonged  1  1/6 (16.67%) 
Lipase increased  1  1/6 (16.67%) 
Serum amylase increased  1  1/6 (16.67%) 
Metabolism and nutrition disorders   
Acidosis  1  1/6 (16.67%) 
Anemia  1  5/6 (83.33%) 
Anorexia  1  2/6 (33.33%) 
Dehydration  1  1/6 (16.67%) 
Hypercalcemia  1  1/6 (16.67%) 
Hyperglycemia  1  4/6 (66.67%) 
Hypermagnesemia  1  3/6 (50.00%) 
Hypertriglyceridemia  1  2/6 (33.33%) 
Hypoalbuminemia  1  6/6 (100.00%) 
Hypocalcemia  1  5/6 (83.33%) 
Hypoglycemia  1  1/6 (16.67%) 
Hypokalemia  1  4/6 (66.67%) 
Hypomagnesemia  1  3/6 (50.00%) 
Hyponatremia  1  6/6 (100.00%) 
Hypophosphatemia  1  5/6 (83.33%) 
Weight loss  1  4/6 (66.67%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  1/6 (16.67%) 
Bone pain  1  1/6 (16.67%) 
Flank pain  1  1/6 (16.67%) 
Generalized muscle weakness  1  1/6 (16.67%) 
Nervous system disorders   
Headache  1  2/6 (33.33%) 
Peripheral motor neuropathy  1  1/6 (16.67%) 
Peripheral sensory neuropathy  1  1/6 (16.67%) 
Psychiatric disorders   
Agitation  1  1/6 (16.67%) 
Renal and urinary disorders   
Urinary tract infection  1  1/6 (16.67%) 
Urine discoloration  1  1/6 (16.67%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  1/6 (16.67%) 
Epistaxis  1  1/6 (16.67%) 
Hypoxia  1  1/6 (16.67%) 
Pleural effusion  1  1/6 (16.67%) 
Pneumothorax  1  1/6 (16.67%) 
Voice alteration  1  1/6 (16.67%) 
Skin and subcutaneous tissue disorders   
Alopecia  1  2/6 (33.33%) 
Dry skin  1  1/6 (16.67%) 
Erythema multiforme  1  1/6 (16.67%) 
Rash maculo-papular  1  1/6 (16.67%) 
Vascular disorders   
Hypertension  1  1/6 (16.67%) 
Hypotension  1  1/6 (16.67%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
[1]
Patient presented with pancreatitis, u/s revealed colonic pneumatosis.
[2]
ferritin=11,000ug/ml on 05/17/11. Hemosiderosis per liver biopsy
The study was terminated early because Enzon Pharmaceuticals decided to halt development of EZN-3042.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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: Peggy Romano, BA, CCRP
Organization: Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) / Children's Hospital Los Angeles
Phone: 323-361-5505
EMail: promano@chla.usc.edu
Layout table for additonal information
Responsible Party: Therapeutic Advances in Childhood Leukemia Consortium
ClinicalTrials.gov Identifier: NCT01186328     History of Changes
Other Study ID Numbers: T2009-007
First Submitted: August 19, 2010
First Posted: August 23, 2010
Results First Submitted: October 3, 2018
Results First Posted: July 24, 2019
Last Update Posted: July 24, 2019