Trial Outcomes & Findings for Combination 5-azacitidine and Gemtuzumab Ozogamicin Therapy for Treatment of Relapsed Acute Myeloid Leukemia (AML) (NCT NCT00766116)
NCT ID: NCT00766116
Last Updated: 2019-02-18
Results Overview
MTD was the maximum number of 5-azacitadine doses (75mg/m2) at which fewer than 1/3 of patients experienced a DLT during cycle 1 of therapy based on CTCAE Version 3.0. In the phase I portion, we assessed 3 dose levels of azacitidine starting on day 1, with 6, 4, and 4 patients in cohort 1, 2, and 3, respectively. We identified no dose-limiting toxicities and identified the phase 2 dose as 75 mg/m2 of 5-azacitadine for 6 days.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
50 participants
Primary outcome timeframe
up to 28 days
Results posted on
2019-02-18
Participant Flow
Participant milestones
| Measure |
Treatment
5-Azacitidine, Gemtuzumab ozogamicin
5-Azacitidine: A = given in cohorts of 3 starting with 2 doses of 5-azacitidine. The doses of 5-azacitidine will be escalated to 4 and then 6 doses if the dose escalation rules permit
Gemtuzumab ozogamicin: M = Mylotarg given 2 times over 2 weeks
|
|---|---|
|
Overall Study
STARTED
|
50
|
|
Overall Study
COMPLETED
|
50
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Combination 5-azacitidine and Gemtuzumab Ozogamicin Therapy for Treatment of Relapsed Acute Myeloid Leukemia (AML)
Baseline characteristics by cohort
| Measure |
Treatment
n=50 Participants
5-Azacitidine, Gemtuzumab ozogamicin
5-Azacitidine: A = given in cohorts of 3 starting with 2 doses of 5-azacitidine. The doses of 5-azacitidine will be escalated to 4 and then 6 doses if the dose escalation rules permit
Gemtuzumab ozogamicin: M = Mylotarg given 2 times over 2 weeks
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
26 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
24 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
26 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
50 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: up to 28 daysMTD was the maximum number of 5-azacitadine doses (75mg/m2) at which fewer than 1/3 of patients experienced a DLT during cycle 1 of therapy based on CTCAE Version 3.0. In the phase I portion, we assessed 3 dose levels of azacitidine starting on day 1, with 6, 4, and 4 patients in cohort 1, 2, and 3, respectively. We identified no dose-limiting toxicities and identified the phase 2 dose as 75 mg/m2 of 5-azacitadine for 6 days.
Outcome measures
| Measure |
Phase 1 Cohort 1
n=6 Participants
5-Azacitidine, Gemtuzumab ozogamicin- Phase 1 Dose Cohort 1: 75 mg/m2 daily for 2 days
|
Phase 1 Cohort 2
n=4 Participants
5-Azacitidine, Gemtuzumab ozogamicin- Phase 1 Dose Cohort 1: 75 mg/m2 daily for 4 days
|
Phase 1 Cohort 3
n=4 Participants
5-Azacitidine, Gemtuzumab ozogamicin- Phase 1 Dose Cohort 1: 75 mg/m2 daily for 6 days
|
|---|---|---|---|
|
Number of Participants With Dose Limiting Toxicities
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Hematologic and Cytogeneic Response to treatment will be assessed when evaluated at the time the ANC has reached 1000/mm3 for three consecutive days, assessed up to 4 yearsOutcome measures
| Measure |
Phase 1 Cohort 1
n=36 Participants
5-Azacitidine, Gemtuzumab ozogamicin- Phase 1 Dose Cohort 1: 75 mg/m2 daily for 2 days
|
Phase 1 Cohort 2
5-Azacitidine, Gemtuzumab ozogamicin- Phase 1 Dose Cohort 1: 75 mg/m2 daily for 4 days
|
Phase 1 Cohort 3
5-Azacitidine, Gemtuzumab ozogamicin- Phase 1 Dose Cohort 1: 75 mg/m2 daily for 6 days
|
|---|---|---|---|
|
Number of Participants With Response to the Combination Treatment of Mylotarg With 5-azacitidine
|
36 Participants
|
—
|
—
|
Adverse Events
Treatment
Serious events: 20 serious events
Other events: 44 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Treatment
n=50 participants at risk
5-Azacitidine, Gemtuzumab ozogamicin
5-Azacitidine: A = given in cohorts of 3 starting with 2 doses of 5-azacitidine. The doses of 5-azacitidine will be escalated to 4 and then 6 doses if the dose escalation rules permit
Gemtuzumab ozogamicin: M = Mylotarg given 2 times over 2 weeks
|
|---|---|
|
Infections and infestations
Pneumonia
|
4.0%
2/50 • Number of events 2
|
|
Gastrointestinal disorders
Abdominal Pain
|
2.0%
1/50 • Number of events 1
|
|
Cardiac disorders
Cardiopulmonary arrest
|
2.0%
1/50 • Number of events 1
|
|
Infections and infestations
Fever
|
2.0%
1/50 • Number of events 1
|
|
Infections and infestations
fever/pneumonia
|
2.0%
1/50 • Number of events 1
|
|
Infections and infestations
Gram (-) Rods
|
2.0%
1/50 • Number of events 1
|
|
Gastrointestinal disorders
nausea, vomiting, abdominal pain
|
2.0%
1/50 • Number of events 1
|
|
Infections and infestations
Hospitalized with syncopal event with intraventricular hemorrhage.
|
2.0%
1/50 • Number of events 1
|
|
Cardiac disorders
Hypotension second to Mylotarg infusion
|
2.0%
1/50 • Number of events 1
|
|
Infections and infestations
Infection documented/ relapsed AML
|
2.0%
1/50 • Number of events 1
|
|
Blood and lymphatic system disorders
Neutropenic Fever
|
22.0%
11/50 • Number of events 13
|
|
Infections and infestations
Refractory platlets
|
2.0%
1/50 • Number of events 1
|
|
Infections and infestations
Sepsis
|
4.0%
2/50 • Number of events 2
|
|
Infections and infestations
SIRS
|
2.0%
1/50 • Number of events 2
|
Other adverse events
| Measure |
Treatment
n=50 participants at risk
5-Azacitidine, Gemtuzumab ozogamicin
5-Azacitidine: A = given in cohorts of 3 starting with 2 doses of 5-azacitidine. The doses of 5-azacitidine will be escalated to 4 and then 6 doses if the dose escalation rules permit
Gemtuzumab ozogamicin: M = Mylotarg given 2 times over 2 weeks
|
|---|---|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
76.0%
38/50 • Number of events 46
|
|
Infections and infestations
Gram Positive Infections
|
14.0%
7/50
|
|
Infections and infestations
Gram Negative Infections
|
4.0%
2/50 • Number of events 2
|
|
Infections and infestations
Pneumonia
|
10.0%
5/50 • Number of events 8
|
|
Blood and lymphatic system disorders
Abnormalities in liver function tests
|
10.0%
5/50 • Number of events 5
|
|
Gastrointestinal disorders
Mucositis
|
12.0%
6/50 • Number of events 6
|
|
Infections and infestations
SIRS/Sepsis
|
10.0%
5/50 • Number of events 5
|
|
General disorders
Weakness
|
10.0%
5/50 • Number of events 15
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
4.0%
2/50 • Number of events 4
|
|
Blood and lymphatic system disorders
Electrolyte abnormalities
|
12.0%
6/50 • Number of events 6
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place