Gemtuzumab Ozogamicin in Treating Patients With Acute Myeloid Leukemia
Primary Purpose
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
gemtuzumab ozogamicin
laboratory biomarker analysis
Sponsored by
About this trial
This is an interventional treatment trial for Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Eligibility Criteria
Inclusion Criteria:
- Patients must have confirmed relapsed or refractory acute myeloid leukemia and not a candidate for standard induction treatment after daunorubicin and cytosine arabinoside OR acute promyelocytic leukemia relapsed after all-trans retinoic acid (ATRA) or Arsenic trioxide therapy
- Patients must have an initial diagnosis of acute myeloid leukemia or biphenotypic acute leukemia
- Patients must have CD33 positivity of >= 30%
- Eastern Cooperative Oncology Group (ECOG) performance status =< 3
- Karnofsky > 60%
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2 X institutional upper limit of normal
- Creatinine within normal institutional limits OR creatinine clearance >= 30 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- The effects of Mylotarg on the developing human fetus are unknown; for this reason and because Mylotarg class agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- Patients may not be receiving any other investigational agents for leukemia
- Patients with known untreated Hepatitis C because veno-occlusive disease and liver enzyme abnormalities have been associated with Mylotarg
- Uncontrolled intercurrent illness including, but not limited to active liver disease, ongoing or active sepsis requiring vasopressors or mechanical ventilation, symptomatic congestive heart failure, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study because Mylotarg is a Class D agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Mylotarg, breastfeeding should be discontinued if the mother is treated with Mylotarg
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Mylotarg; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
- Congestive Heart Failure (CHF) with an ejection fraction < 30%
- Glomerular filtration rate (GFR) < 30ml/min
- Active central nervous system (CNS) involvement of leukemia
- Philadelphia chromosome + acute lymphoblastic leukemia (ALL)
- Prior hematopoietic transplant in last 3 months
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (monoclonal antibody therapy)
Arm Description
Patients receive gemtuzumab ozogamicin IV over 2 hours on days 1 and 15. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.
Outcomes
Primary Outcome Measures
Rate of serious adverse events
95% confidence interval will be calculated. Graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Secondary Outcome Measures
Overall response, defined as complete remission (CR) and CR with incomplete platelet recovery (CRp)
Safety analysis of gemtuzumab ozogamicin as induction therapy for patients with relapsed AML
Adverse event frequency and severity
Overall survival (OS)
Event-free survival (EFS)
Disease free survival (DFS)
Full Information
NCT ID
NCT01548911
First Posted
February 14, 2012
Last Updated
June 29, 2018
Sponsor
Wake Forest University Health Sciences
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT01548911
Brief Title
Gemtuzumab Ozogamicin in Treating Patients With Acute Myeloid Leukemia
Official Title
Safety and Efficacy of Gemtuzumab Ozogamicin (Mylotarg®) as for Treatment of Patients With CD33-Positive Acute Myeloid Leukemia (AML)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2018
Overall Recruitment Status
Withdrawn
Study Start Date
May 2012 (undefined)
Primary Completion Date
September 2013 (Actual)
Study Completion Date
September 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wake Forest University Health Sciences
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This clinical trial studies the side effects of gemtuzumab ozogamicin and how well it works in treating patients with acute myeloid leukemia. Monoclonal antibodies, such as gemtuzumab ozogamicin, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them
Detailed Description
PRIMARY OBJECTIVES:
I. To study safety and efficacy single agent Gemtuzumab Ozogamicin (Mylotarg®) as induction therapy for patients with Acute Myeloid Leukemia (AML) who have relapsed after standard treatments or who are not candidates for standard consolidation treatment after Daunorubicin and cytosine arabinoside.
SECONDARY OBJECTIVES:
I. To correlate morbidity and mortality with the use of gemtuzumab (gemtuzumab ozogamicin) to specific subtypes of leukemia.
II. To correlate gemtuzumab response to degree of cluster of differentiation (CD) 33 positivity.
III. To correlate FMS-Related Tyrosine Kinase 3 (FLT 3)/nucleophosmin (NPM) status and CD 33 positivity to gemtuzumab response.
IV. To document incidence of sinusoidal obstruction syndrome with the use of gemtuzumab.
OUTLINE:
Patients receive gemtuzumab ozogamicin intravenously (IV) over 2 hours on days 1 and 15. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up monthly for 1 year.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Adult Acute Promyelocytic Leukemia (M3), Recurrent Adult Acute Myeloid Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment (monoclonal antibody therapy)
Arm Type
Experimental
Arm Description
Patients receive gemtuzumab ozogamicin IV over 2 hours on days 1 and 15. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
gemtuzumab ozogamicin
Other Intervention Name(s)
Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody, CDP-771, CMA-676, Mylotarg
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Rate of serious adverse events
Description
95% confidence interval will be calculated. Graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Time Frame
Approximately 1 year
Secondary Outcome Measure Information:
Title
Overall response, defined as complete remission (CR) and CR with incomplete platelet recovery (CRp)
Time Frame
At 28 days
Title
Safety analysis of gemtuzumab ozogamicin as induction therapy for patients with relapsed AML
Description
Adverse event frequency and severity
Time Frame
Approximately 1 year
Title
Overall survival (OS)
Time Frame
Approximately 1 year
Title
Event-free survival (EFS)
Time Frame
Approximately 1 year
Title
Disease free survival (DFS)
Time Frame
Approximately 1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients must have confirmed relapsed or refractory acute myeloid leukemia and not a candidate for standard induction treatment after daunorubicin and cytosine arabinoside OR acute promyelocytic leukemia relapsed after all-trans retinoic acid (ATRA) or Arsenic trioxide therapy
Patients must have an initial diagnosis of acute myeloid leukemia or biphenotypic acute leukemia
Patients must have CD33 positivity of >= 30%
Eastern Cooperative Oncology Group (ECOG) performance status =< 3
Karnofsky > 60%
Total bilirubin within normal institutional limits
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2 X institutional upper limit of normal
Creatinine within normal institutional limits OR creatinine clearance >= 30 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
The effects of Mylotarg on the developing human fetus are unknown; for this reason and because Mylotarg class agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
Patients may not be receiving any other investigational agents for leukemia
Patients with known untreated Hepatitis C because veno-occlusive disease and liver enzyme abnormalities have been associated with Mylotarg
Uncontrolled intercurrent illness including, but not limited to active liver disease, ongoing or active sepsis requiring vasopressors or mechanical ventilation, symptomatic congestive heart failure, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant women are excluded from this study because Mylotarg is a Class D agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Mylotarg, breastfeeding should be discontinued if the mother is treated with Mylotarg
Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Mylotarg; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
Congestive Heart Failure (CHF) with an ejection fraction < 30%
Glomerular filtration rate (GFR) < 30ml/min
Active central nervous system (CNS) involvement of leukemia
Philadelphia chromosome + acute lymphoblastic leukemia (ALL)
Prior hematopoietic transplant in last 3 months
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Leslie Ellis, MD
Organizational Affiliation
Wake Forest University Health Sciences
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Gemtuzumab Ozogamicin in Treating Patients With Acute Myeloid Leukemia
We'll reach out to this number within 24 hrs