Trial Outcomes & Findings for EZN-3042 Administered With Re-induction Chemotherapy in Children With Relapsed Acute Lymphoblastic Leukemia (ALL) (NCT NCT01186328)
NCT ID: NCT01186328
Last Updated: 2024-02-01
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE1
Target enrollment
6 participants
Primary outcome timeframe
2 months
Results posted on
2024-02-01
Participant Flow
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.
Participant milestones
| Measure |
EZN Dose Level 1
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.
|
EZN Dose Level 2
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.
|
EZN Dose Level 3
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.
|
|---|---|---|---|
|
Overall Study
STARTED
|
6
|
0
|
0
|
|
Overall Study
COMPLETED
|
5
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
EZN Dose Level 1
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.
|
EZN Dose Level 2
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.
|
EZN Dose Level 3
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.
|
|---|---|---|---|
|
Overall Study
Death
|
1
|
0
|
0
|
Baseline Characteristics
EZN-3042 Administered With Re-induction Chemotherapy in Children With Relapsed Acute Lymphoblastic Leukemia (ALL)
Baseline characteristics by cohort
| Measure |
EZN Dose Level 1
n=6 Participants
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.
|
|---|---|
|
Age, Categorical
<=18 years
|
5 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Prior HSCT
Yes
|
2 Participants
n=5 Participants
|
|
Prior HSCT
No
|
4 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 2 monthsPopulation: 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.
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.
Outcome measures
| Measure |
EZN Dose Level 1
n=6 Participants
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.
|
EZN Dose Level 0
Study deescalated to Dose Level 0 at 1.5 mg/kg after 2 patients at Dose Level 1 experienced DLTs.
|
|---|---|---|
|
Maximum Tolerated Dose of EZN-3042
Completed therapy w/o DLT
|
4 Participants
|
0 Participants
|
|
Maximum Tolerated Dose of EZN-3042
Experienced DLT
|
2 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day -6 to Day 0Population: Five patients provided samples for pharmacokinetic analysis.
To evaluate primary target engagement of EZN-3042 we will examine survivin transcript and protein expression before (Day -6) and after EZN-3042 administration (Day 0) in enriched bone marrow blasts in children with relapsed B-precursor leukemia.
Outcome measures
| Measure |
EZN Dose Level 1
n=5 Participants
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.
|
EZN Dose Level 0
Study deescalated to Dose Level 0 at 1.5 mg/kg after 2 patients at Dose Level 1 experienced DLTs.
|
|---|---|---|
|
Number of Participants Who Showed a Decrease From Day -6 in Survivin Transcript Expression After EZN-3042 Administration
|
2 Participants
|
—
|
Adverse Events
EZN Dose Level 1
Serious events: 3 serious events
Other events: 6 other events
Deaths: 4 deaths
Serious adverse events
| Measure |
EZN Dose Level 1
n=6 participants at risk
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.
|
|---|---|
|
Investigations
Aspartate aminotransferase increased
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Investigations
GGT increased
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Infections and infestations
Lung infection
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Infections and infestations
Enterocolitis infectious
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Gastrointestinal disorders
Gastric hemorrhage
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Infections and infestations
Sepsis
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Gastrointestinal disorders
Pancreatitis
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
Other adverse events
| Measure |
EZN Dose Level 1
n=6 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
33.3%
2/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Metabolism and nutrition disorders
Acidosis
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Investigations
Activated partial thromboplastin time prolonged
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Psychiatric disorders
Agitation
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Investigations
Alanine aminotransferase increased
|
83.3%
5/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Investigations
Alkaline phosphatase increased
|
33.3%
2/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
33.3%
2/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Metabolism and nutrition disorders
Anemia
|
83.3%
5/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Metabolism and nutrition disorders
Anorexia
|
33.3%
2/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Investigations
Aspartate aminotransferase increased
|
50.0%
3/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Investigations
Blood bilirubin increased
|
33.3%
2/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Injury, poisoning and procedural complications
Bruising
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Metabolism and nutrition disorders
Dehydration
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Gastrointestinal disorders
Diarrhea
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Ear and labyrinth disorders
Ear pain
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Investigations
Electrocardiogram QT corrected interval prolonged
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Infections and infestations
Enterocolitis infectious
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Skin and subcutaneous tissue disorders
Erythema multiforme
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
General disorders
Fatigue
|
33.3%
2/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
General disorders
Fever
|
50.0%
3/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, specify
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Nervous system disorders
Headache
|
33.3%
2/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Hepatobiliary disorders
Hepatobiliary disorders - Other, specify
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
66.7%
4/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
50.0%
3/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Vascular disorders
Hypertension
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
33.3%
2/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
100.0%
6/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
83.3%
5/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
66.7%
4/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
50.0%
3/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
100.0%
6/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
83.3%
5/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Vascular disorders
Hypotension
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
General disorders
Infusion site extravasation
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Blood and lymphatic system disorders
Leukocytosis
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Investigations
Lipase increased
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Blood and lymphatic system disorders
Lymphocyte count decreased
|
50.0%
3/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Gastrointestinal disorders
Mucositis oral
|
83.3%
5/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Gastrointestinal disorders
Nausea
|
50.0%
3/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Blood and lymphatic system disorders
Neutrophil count decreased
|
66.7%
4/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Gastrointestinal disorders
Oral pain
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
General disorders
Pain
|
50.0%
3/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Cardiac disorders
Pericardial effusion
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Nervous system disorders
Peripheral motor neuropathy
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Blood and lymphatic system disorders
Platelet count decreased
|
100.0%
6/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Investigations
Serum amylase increased
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Cardiac disorders
Sinus tachycardia
|
33.3%
2/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Cardiac disorders
Supraventricular tachycardia
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Renal and urinary disorders
Urinary tract infection
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Renal and urinary disorders
Urine discoloration
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Respiratory, thoracic and mediastinal disorders
Voice alteration
|
16.7%
1/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Gastrointestinal disorders
Vomiting
|
50.0%
3/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Metabolism and nutrition disorders
Weight loss
|
66.7%
4/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
|
Blood and lymphatic system disorders
White blood cell decreased
|
83.3%
5/6 • 11 months
The definitions of AE and SAE used to collect information do not differ from the clinicaltrials.gov definitions.
|
Additional Information
Peggy Romano, BA, CCRP
Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) / Children's Hospital Los Angeles
Phone: 323-361-5505
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60