Combination 5-azacitidine and Gemtuzumab Ozogamicin Therapy for Treatment of Relapsed Acute Myeloid Leukemia (AML)

• Sponsor: University of California, San Diego (Other)
• Overall Status: Completed
• CT.gov ID: NCT00766116
• Collaborator: Celgene Corporation (Industry), Pfizer (Industry)
• Enrollment: 50
• Locations: 3
• Arms: 4
• Actual Duration (Months): 110.9
• Patients Per Site: 16.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study will test an experimental combination of the drugs Mylotarg and 5-azacitidine in the hopes of finding a treatment that may be effective against Acute Myeloid Leukemia that has come back after treatment.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: 5-Azacitidine; Drug: Gemtuzumab ozogamicin	Phase 1/Phase 2

Detailed Description

In the Phase I portion of the study patients with a diagnosis of AML who have relapsed disease will be treated with an assigned number of doses of 5 azacitidine followed by Mylotarg administered two times over two weeks

In the Phase II portion of the study patients will be treated with the dose of 5azacitidine determined to be safe in the Phase I portion of the study followed by Mylotarg.

A sample of blood or bone marrow will be obtained prior to initiation of treatment and another sample obtained after treatment with 5-azacitidine but before Mylotarg and the samples will be tested in the laboratory to determine response to treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Trial of the Combination 5-azacitidine and Gemtuzumab Ozogamicin Therapy for Treatment of Relapsed AML
• Actual Study Start Date: Jul 1, 2005
• Actual Primary Completion Date: Sep 26, 2014
• Actual Study Completion Date: Sep 26, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1 Dose Level 1 5-Azacitidine, Gemtuzumab ozogamicin 75 mg/m^2 5-Aza 2 days then GO at 3 mg/m^2	Drug: 5-Azacitidine; 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.; Other Names: Vidaz ; Drug: Gemtuzumab ozogamicin; Mylotarg given 2 times over 2 weeks; Other Names: Mylotarg
Experimental: Phase 1 Dose Level 2 5-Azacitidine, Gemtuzumab ozogamicin 75mg/m^2 5-Aza for 4 days then GO at 6 mg/m^2	Drug: 5-Azacitidine; 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.; Other Names: Vidaz ; Drug: Gemtuzumab ozogamicin; Mylotarg given 2 times over 2 weeks; Other Names: Mylotarg
Experimental: Phase I Dose Level 3 5-Azacitidine, Gemtuzumab ozogamicin 75 mg/m^2 5-Aza for 6 days then GO at 6 mg/m^2	Drug: 5-Azacitidine; 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.; Other Names: Vidaz ; Drug: Gemtuzumab ozogamicin; Mylotarg given 2 times over 2 weeks; Other Names: Mylotarg
Experimental: Phase 2 Dose Level 1 5-Azacitidine, Gemtuzumab ozogamicin 75 mg/m^2 5-Aza for 6 days then GO at 6 mg/m^2	Drug: 5-Azacitidine; 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.; Other Names: Vidaz ; Drug: Gemtuzumab ozogamicin; Mylotarg given 2 times over 2 weeks; Other Names: Mylotarg

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Dose Limiting Toxicities [up to 28 days]

   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.

Secondary Outcome Measures

1. Number of Participants With Response to the Combination Treatment of Mylotarg With 5-azacitidine [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 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of Relapsed AML

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2, and life expectancy

3 months

• ≥ 18 years old

• Previously untreated for current AML relapse

• Adequate organ function

• Written informed consent

Exclusion Criteria:

• Pregnant or breast-feeding women

• Growth factors that support platelet or white cell number or function must not have been administered within the past 7 days

• Currently receiving another investigational drug

• Currently receiving other anti-cancer agents

• Uncontrolled infection

• HIV positive

• Received previous therapy with either Mylotarg or 5-azacitidine

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSD Moores Cancer Center	La Jolla	California	United States	92093
2	Stanford University	Stanford	California	United States	94305
3	Northside Hospital/BMTGA	Atlanta	Georgia	United States	30342

Sponsors and Collaborators

• University of California, San Diego
• Celgene Corporation
• Pfizer

Investigators

• Principal Investigator: Edward D Ball, MD, UCSD

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Edward Ball, Professor of medicine, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT00766116
• Other Study ID Numbers: 090516
• First Posted: Oct 3, 2008
• Last Update Posted: Feb 18, 2019
• Last Verified: Jan 1, 2019

• Keywords provided by Edward Ball, Professor of medicine, University of California, San Diego: AML
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Azacitidine; Gemtuzumab

Study Results

Participant Flow

Arm/Group Title	Treatment
Arm/Group Description	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
Period Title: Overall Study
STARTED	50
COMPLETED	50
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment
Arm/Group Description	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 Participants	50
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	26 52%
>=65 years	24 48%
Sex: Female, Male (Count of Participants)
Female	26 52%
Male	24 48%
Region of Enrollment (Count of Participants)
United States	50 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Dose Limiting Toxicities
Description	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.
Time Frame	up to 28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 1 Cohort 1	Phase 1 Cohort 2	Phase 1 Cohort 3
Arm/Group Description	5-Azacitidine, Gemtuzumab ozogamicin- Phase 1 Dose Cohort 1: 75 mg/m2 daily for 2 days	5-Azacitidine, Gemtuzumab ozogamicin- Phase 1 Dose Cohort 1: 75 mg/m2 daily for 4 days	5-Azacitidine, Gemtuzumab ozogamicin- Phase 1 Dose Cohort 1: 75 mg/m2 daily for 6 days
Measure Participants	6	4	4
Count of Participants [Participants]	0 0%	0 NaN	0 NaN

2. Secondary Outcome

Title	Number of Participants With Response to the Combination Treatment of Mylotarg With 5-azacitidine
Time Frame	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 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group Description	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
Measure Participants	36
Count of Participants [Participants]	36 72%

Adverse Events

Arm/Group Title	Treatment
Arm/Group Description	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
All Cause Mortality
	Treatment
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	20/50 (40%)
Blood and lymphatic system disorders
Neutropenic Fever	11/50 (22%)	13
Cardiac disorders
Cardiopulmonary arrest	1/50 (2%)	1
Hypotension second to Mylotarg infusion	1/50 (2%)	1
Gastrointestinal disorders
Abdominal Pain	1/50 (2%)	1
nausea, vomiting, abdominal pain	1/50 (2%)	1
Infections and infestations
Pneumonia	2/50 (4%)	2
Fever	1/50 (2%)	1
fever/pneumonia	1/50 (2%)	1
Gram (-) Rods	1/50 (2%)	1
Hospitalized with syncopal event with intraventricular hemorrhage.	1/50 (2%)	1
Infection documented/ relapsed AML	1/50 (2%)	1
Refractory platlets	1/50 (2%)	1
Sepsis	2/50 (4%)	2
SIRS	1/50 (2%)	2
Other (Not Including Serious) Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	44/50 (88%)
Blood and lymphatic system disorders
Febrile Neutropenia	38/50 (76%)	46
Abnormalities in liver function tests	5/50 (10%)	5
Electrolyte abnormalities	6/50 (12%)	6
Gastrointestinal disorders
Mucositis	6/50 (12%)	6
General disorders
Weakness	5/50 (10%)	15
Infections and infestations
Gram Positive Infections	7/50 (14%)
Gram Negative Infections	2/50 (4%)	2
Pneumonia	5/50 (10%)	8
SIRS/Sepsis	5/50 (10%)	5
Respiratory, thoracic and mediastinal disorders
Respiratory failure	2/50 (4%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.