Fractionated Gemtuzumab Ozogamicin in Treating Measurable Residual Disease in Patients With Acute Myeloid Leukemia

Sponsor

University of Washington (Other)

Overall Status

Recruiting

CT.gov ID

NCT03737955

Collaborator

Pfizer (Industry)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase II trial studies the how well fractionated gemtuzumab ozogamicin works in treating measurable residual disease in patients with acute myeloid leukemia. Gemtuzumab ozogamicin is a monoclonal antibody, called gemtuzumab, linked to a chemotherapy drug, called ozogamicin. Gemtuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD33 receptors, and delivers a chemotherapy known as calicheamicin to kill them.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: Gemtuzumab Ozogamicin Other: Quality-of-Life Assessment	Phase 2

Detailed Description

OUTLINE:

Patients receive gemtuzumab ozogamicin intravenously (IV) on days 1, 4, 7. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity. Responders and non-responders, without significant adverse events during the first course, may receive a second course of gemtuzumab ozogamicin within 60 days after course 1.

After completion of study treatment, patients are followed up for 6 months.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

36 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2 Trial of Fractionated Gemtuzumab Ozogamicin to Eradicate Measurable Residual Disease in Acute Myeloid Leukemia Patients (GO for MRD)

Actual Study Start Date :

Nov 30, 2018

Anticipated Primary Completion Date :

Jun 1, 2024

Anticipated Study Completion Date :

Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (gemtuzumab ozogamicin) Patients receive gemtuzumab ozogamicin IV on days 1, 4, 7. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity. Responders and non-responders, without significant adverse events during the first course, may receive a second course of gemtuzumab ozogamicin within 60 days after course 1.	Drug: Gemtuzumab Ozogamicin Receive IV Other Names: CDP-771 Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody Mylotarg Other: Quality-of-Life Assessment Ancillary studies Other Names: Quality of Life Assessment

Arm

Intervention/Treatment

Experimental: Treatment (gemtuzumab ozogamicin)

Patients receive gemtuzumab ozogamicin IV on days 1, 4, 7. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity. Responders and non-responders, without significant adverse events during the first course, may receive a second course of gemtuzumab ozogamicin within 60 days after course 1.

Drug: Gemtuzumab Ozogamicin

Receive IV

Other Names:

CDP-771

Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody

Mylotarg

Other: Quality-of-Life Assessment

Ancillary studies

Other Names:

Quality of Life Assessment

Outcome Measures

Primary Outcome Measures

Clinical response rate [Up to 70 days]
Measured by clearance of measurable residual disease (MRD) with bone marrow evaluation after one or two cycles of therapy and compare responses (rate of eradication of MRD) based on CD33 single nucleotide polymorphism rs12459419 genotype.

Secondary Outcome Measures

Rate of sinusoidal obstructive syndrome (SOS) [Up to 6 months]
Measured by grade III/IV non-hematologic toxicities using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.
Rate of allogeneic hematopoietic cell transplantation (HCT) [Up to 6 Months]
Measured by those receiving HCT

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Prior diagnosis AML based on 2016 World Health Organization criteria. Acute promyelocytic leukemia (APL) and biphenotypic AML are not eligible.
Patients must have MRD-level disease only and otherwise meet criteria for complete response (CR) or complete remission with incomplete hematologic recovery (CRi) per the 2017 European Leukemia Net response criteria (< 5% blasts in the marrow without a requirement for peripheral blood count recovery). MRD must be measurable by multiparameter flow cytometry (MPFC) and/or polymerase chain reaction (PCR)-based molecular markers and/or karyotypic markers (e.g., classical cytogenetics or fluorescence in situ hybridization). MRD status will be centrally confirmed by the UW/FHCRC clinical laboratory in order to standardize response assessment following administration of study therapy.
Patients must have received at least 1 cycle of standard induction chemotherapy prior to enrollment on the study. However, adult patients (>= 18 years of age) are eligible for participation at any time point in treatment (after induction, during or after consolidation, pre-transplant, or post-transplant). Pediatric patients (2-18 years of age) must have MRD positivity during/after consolidation or post-transplant.
Age >= 2 years of age
Eastern Cooperative Oncology Group (ECOG) performance status =< 3 (for adults) or Lansky performance status >= 40 (for children).
Patient's AML blasts must have CD33 expression.
For adults (>= 18 years of age): Serum creatinine =< 2.0 mg/dL.
For adults (>= 18 years of age): Total bilirubin =< 2 x institutional upper limit of normal for age (unless known history of Gilbert's disease).
For adults (>= 18 years of age): Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x institutional upper limit of normal for age (unless thought to be related to resolving infectious complications).
For children (< 18 years of age): Glomerular filtration rate (GFR) in ml/min (age 2: 63-175; age 3-12: 89-165; females 13 and older: 75-115; males 13 and older: 85-125).
For children (< 18 years of age): Total bilirubin =< 2 x institutional upper limit of normal for age (unless known history of Gilbert's disease).
For children (< 18 years of age): AST and ALT < 2.5 x institutional upper limit of normal for age (unless thought to be related to resolving infectious complications).
Ability of patient or representative to provide written informed consent.
Females of childbearing potential must have a negative pregnancy test prior to receiving GO.
Patients who re-enroll must have achieved an MRD-negative CR during their prior enrollment

Exclusion Criteria:

Subjects who have had chemotherapy or radiation therapy within 14 days prior to entering the study.
Subjects may not be receiving other investigational agents.
Uncontrolled or concurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.