Acute Myeloid Leukemia
Conditions
Keywords
AML
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.
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.
Interventions
DRUG5-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.
DRUGGemtuzumab ozogamicin
Mylotarg given 2 times over 2 weeks
Sponsors
Celgene Corporation
Pfizer
University of California, San Diego
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 50 |
| Total | 50 |
Baseline characteristics
| Characteristic | Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 24 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants |
| Region of Enrollment United States | 50 Participants |
| Sex: Female, Male Female | 26 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 44 / 50 |
| serious Total, serious adverse events | 20 / 50 |
Outcome results
Primary
Number of Participants With Dose Limiting Toxicities
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1 Cohort 1 | Number of Participants With Dose Limiting Toxicities | 0 Participants |
| Phase 1 Cohort 2 | Number of Participants With Dose Limiting Toxicities | 0 Participants |
| Phase 1 Cohort 3 | Number of Participants With Dose Limiting Toxicities | 0 Participants |
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1 Cohort 1 | Number of Participants With Response to the Combination Treatment of Mylotarg With 5-azacitidine | 36 Participants |