Trial Outcomes & Findings for Phase I/II, Open-label, Multi-center, Two Part Dose-escalation, Safety, Pharmacokinetics (PK) and Efficacy Study of AZD4877 in Patients With Acute Myelogenous Leukemia (AML) (NCT NCT00486265)
NCT ID: NCT00486265
Last Updated: 2010-12-21
Results Overview
To identify a maximum tolerated dose (MTD) of AZD4877 by assessment of the incidence of dose-limiting toxicities (DLTs)
TERMINATED
PHASE1
47 participants
Dose-limiting toxicities (DLTs) are evaluated during the first induction treatment course administered during the initial 15-day treatment period.
2010-12-21
Participant Flow
Participants were recruited at 4 study sites in the United States and 1 study site in Canada between July 2007 and February 2009 \[Part A\] and between March 2009 and July 2009 \[Part B\].
Following enrolment there was screening period of up to 28 days, after which if all inclusion/exclusion criteria were met, patients were dosed with AZD4877
Participant milestones
| Measure |
AZD4877
AZD4877 \[ Time Frame: administered on days 1,2 and 3\]
|
|---|---|
|
Overall Study
STARTED
|
9
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
9
|
Reasons for withdrawal
| Measure |
AZD4877
AZD4877 \[ Time Frame: administered on days 1,2 and 3\]
|
|---|---|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Lack of Efficacy
|
8
|
Baseline Characteristics
Phase I/II, Open-label, Multi-center, Two Part Dose-escalation, Safety, Pharmacokinetics (PK) and Efficacy Study of AZD4877 in Patients With Acute Myelogenous Leukemia (AML)
Baseline characteristics by cohort
| Measure |
AZD4877
n=9 Participants
AZD4877 \[ Time Frame: administered on days 1,2 and 3\]
|
|---|---|
|
Age, Customized
< 18 Years
|
0 Participants
n=5 Participants
|
|
Age, Customized
>=18 - < 65 Years
|
6 Participants
n=5 Participants
|
|
Age, Customized
>=65 - < 75 Yrs
|
1 Participants
n=5 Participants
|
|
Age, Customized
>=75 Yrs
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
8 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Dose-limiting toxicities (DLTs) are evaluated during the first induction treatment course administered during the initial 15-day treatment period.To identify a maximum tolerated dose (MTD) of AZD4877 by assessment of the incidence of dose-limiting toxicities (DLTs)
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Response is evaluated after a maximum of 2 courses of induction therapy.Population: 8 of 9 patients in Part B were evaluable for response following a maximum of 2 courses of induction therapy.
Marrow response is assessed by modified Cheson criteria for Acute Myelogenous Leukemia (AML). Possible outcomes for marrow response are CR (Complete Remission), CRi (Complete Remission with incomplete blood count recovery), PR (Partial Remission), and treatment failure.
Outcome measures
| Measure |
AZD4877
n=8 Participants
AZD4877 \[ Time Frame: administered on days 1,2 and 3\]
|
|---|---|
|
To Assess the Effect of AZD4877 on the Rate of Complete Remission (CR)
|
0 Participants
|
PRIMARY outcome
Timeframe: PK samples are collected on Days 1, 2, 3, 24 and 48 hours following the end of Day 3 AZD4877 infusion and Day 8.Maximum plasma concentration, Cmax
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Response is evaluated after a maximum of 2 courses of induction therapy.Marrow response is assessed by modified Cheson criteria for Acute Myelogenous Leukemia (AML). Possible outcomes for marrow response are CR (Complete Remission), CRi (Complete Remission with incomplete blood count recovery), PR (Partial Remission), and treatment failure.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Patients were followed for safety from the date of first dose of AZD4877 up to 30-days after the last administration of AZD4877, where possible.Outcome measures
Outcome data not reported
Adverse Events
AZD4877
Serious adverse events
| Measure |
AZD4877
n=9 participants at risk
AZD4877 \[ Time Frame: administered on days 1,2 and 3\]
|
|---|---|
|
General disorders
Mucosal Inflammation
|
33.3%
3/9
|
|
Skin and subcutaneous tissue disorders
Stevens-Johnson Syndrome
|
11.1%
1/9
|
Other adverse events
| Measure |
AZD4877
n=9 participants at risk
AZD4877 \[ Time Frame: administered on days 1,2 and 3\]
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
11.1%
1/9
|
|
Blood and lymphatic system disorders
Leukopenia
|
11.1%
1/9
|
|
Blood and lymphatic system disorders
Neutropenia
|
11.1%
1/9
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
11.1%
1/9
|
|
Cardiac disorders
Sinus Tachycardia
|
11.1%
1/9
|
|
Congenital, familial and genetic disorders
Hypophosphatasia
|
11.1%
1/9
|
|
Ear and labyrinth disorders
Ear Pain
|
11.1%
1/9
|
|
Eye disorders
Dry Eye
|
11.1%
1/9
|
|
Gastrointestinal disorders
Constipation
|
33.3%
3/9
|
|
Gastrointestinal disorders
Diarrhoea
|
33.3%
3/9
|
|
Gastrointestinal disorders
Nausea
|
33.3%
3/9
|
|
Gastrointestinal disorders
Abdominal Pain
|
11.1%
1/9
|
|
Gastrointestinal disorders
Dysphagia
|
11.1%
1/9
|
|
General disorders
Mucosal Inflammation
|
66.7%
6/9
|
|
General disorders
Fatigue
|
33.3%
3/9
|
|
General disorders
Oedema Peripheral
|
22.2%
2/9
|
|
General disorders
Asthenia
|
11.1%
1/9
|
|
General disorders
Chills
|
11.1%
1/9
|
|
General disorders
Oedema
|
11.1%
1/9
|
|
Hepatobiliary disorders
Hepatic Cyst
|
11.1%
1/9
|
|
Hepatobiliary disorders
Hepatic Lesion
|
11.1%
1/9
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
11.1%
1/9
|
|
Infections and infestations
Ear Infection
|
11.1%
1/9
|
|
Infections and infestations
Pneumonia
|
11.1%
1/9
|
|
Injury, poisoning and procedural complications
Limb Injury
|
11.1%
1/9
|
|
Injury, poisoning and procedural complications
Transfusion Reaction
|
11.1%
1/9
|
|
Investigations
Activated Partial Thromboplastin Time Prolonged
|
11.1%
1/9
|
|
Investigations
Alanine Aminotransferase Increased
|
11.1%
1/9
|
|
Investigations
Aspartate Aminotransferase Increased
|
11.1%
1/9
|
|
Investigations
Blood Creatinine Increased
|
11.1%
1/9
|
|
Investigations
Blood Phosphorus Increased
|
11.1%
1/9
|
|
Investigations
Blood Pressure Orthostatic Decreased
|
11.1%
1/9
|
|
Investigations
Transaminases Increased
|
11.1%
1/9
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
55.6%
5/9
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
55.6%
5/9
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
44.4%
4/9
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
33.3%
3/9
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
33.3%
3/9
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
22.2%
2/9
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
22.2%
2/9
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
22.2%
2/9
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
22.2%
2/9
|
|
Metabolism and nutrition disorders
Hyperphosphataemia
|
11.1%
1/9
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
11.1%
1/9
|
|
Musculoskeletal and connective tissue disorders
Pain In Extremity
|
11.1%
1/9
|
|
Musculoskeletal and connective tissue disorders
Pain In Jaw
|
11.1%
1/9
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Haemangioma Of Liver
|
11.1%
1/9
|
|
Nervous system disorders
Headache
|
33.3%
3/9
|
|
Nervous system disorders
Neuropathy Peripheral
|
22.2%
2/9
|
|
Nervous system disorders
Dizziness
|
11.1%
1/9
|
|
Nervous system disorders
Syncope
|
11.1%
1/9
|
|
Psychiatric disorders
Insomnia
|
22.2%
2/9
|
|
Psychiatric disorders
Depression
|
11.1%
1/9
|
|
Psychiatric disorders
Mood Altered
|
11.1%
1/9
|
|
Renal and urinary disorders
Dysuria
|
11.1%
1/9
|
|
Renal and urinary disorders
Haematuria
|
11.1%
1/9
|
|
Renal and urinary disorders
Proteinuria
|
11.1%
1/9
|
|
Renal and urinary disorders
Renal Cyst
|
11.1%
1/9
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
22.2%
2/9
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
11.1%
1/9
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
11.1%
1/9
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Oedema
|
11.1%
1/9
|
|
Skin and subcutaneous tissue disorders
Rash
|
22.2%
2/9
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
11.1%
1/9
|
|
Skin and subcutaneous tissue disorders
Skin Irritation
|
11.1%
1/9
|
|
Skin and subcutaneous tissue disorders
Stevens-Johnson Syndrome
|
11.1%
1/9
|
|
Vascular disorders
Hypotension
|
22.2%
2/9
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The PI agrees to provide a copy of the publication to AZ for review at least 60 days in advance of submission for publication. Investigators in multicenter (MC) studies agree to postpone MC publications until the earlier of the date of the first AZ authorized MC publication or a period up to 18 months from study completion at all sites. AZ has the right to request delays: up to 60 days for confidential information, and an additional 90 days to protect intellectual property.
- Publication restrictions are in place
Restriction type: OTHER