Description:
This is a single-arm, open-label, Phase 4 study evaluating the effect of GO on the QTc,
pharmacokinetics, safety, and immunogenicity of GO as a single-agent monotherapy in adult and
pediatric patients with relapsed or refractory CD33-positive AML.
Title
- Brief Title: Evaluating QTc, PK, Safety of Gemtuzumab Ozogamicin (GO) in Patients With CD33+ R/R AML
- Official Title: A SINGLE ARM, OPEN-LABEL, PHASE 4 STUDY EVALUATING QT INTERVAL, PHARMACOKINETICS, AND SAFETY OF GEMTUZUMAB OZOGAMICIN (MYLOTARG (TRADEMARKER)) AS A SINGLE-AGENT REGIMEN IN PATIENTS WITH RELAPSED OR REFRACTORY CD33-POSITIVE ACUTE MYELOID LEUKEMIA
Clinical Trial IDs
- ORG STUDY ID:
B1761031
- SECONDARY ID:
2018-002619-89
- NCT ID:
NCT03727750
Conditions
- ECG
- Pharmacokinetics
- Safety
Interventions
| Drug | Synonyms | Arms |
|---|
| Gemtuzumab Ozogamicin | | Gemtuzumab Ozogamicin (GO) |
Purpose
This is a single-arm, open-label, Phase 4 study evaluating the effect of GO on the QTc,
pharmacokinetics, safety, and immunogenicity of GO as a single-agent monotherapy in adult and
pediatric patients with relapsed or refractory CD33-positive AML.
Detailed Description
This is a single-arm, open-label, Phase 4 study evaluating the effect of GO on the QTc,
pharmacokinetics, safety, and immunogenicity of GO as a single-agent monotherapy in adult and
pediatric patients with relapsed or refractory CD33-positive AML. Approximately 50 adult (age
>=18 years) and 6 pediatric (12 years =< age =< 17 years) patients who satisfy the study
eligibility criteria will be enrolled. Enrolled patients will receive GO 3 mg/m2 up to 2
cycles on Days 1, 4, and 7 at each cycle. The impact of GO on VOD/SOS in the context of
previous and subsequent HSCT will also be assessed. Patients enrolled in the study will
receive three doses of GO 3 mg/m2 (up to one vial) as a 2-hour intravenous infusion on Cycle
1 Days 1, 4, and 7. A second cycle of GO 3mg/m² (up to one vial) on Cycle 2 Days 1, 4, and 7
will be allowed at the investigator's discretion for patients who meet the following criteria
after Cycle 1: Bone marrow with a decrease of blast percentage to at least 25% or a decrease
of pretreatment blast percentage by at least 50%; and Blood count with neutrophils
>=1,000/µL, and platelets >=50,000/µL, except in patients with the bone marrow blasts >=5%,
the decrease in neutrophils and platelets thought to be due to the underlying leukemia. After
GO treatment, subsequent anticancer therapy such as consolidation or conditioning regimen
and/or HSCT could be considered at the investigator's discretion. A minimum interval of 2
months is recommended between the last dose of GO and HSCT.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Gemtuzumab Ozogamicin (GO) | Experimental | Patients will receive three doses of Gemtuzumab Ozogamicin (GO) 3 mg/m2 (up to one vial) as a 2 hour intravenous infusion on Cycle 1 Days 1, 4, and 7. A second cycle of GO 3mg/m² (up to one vial) on Cycle 2 Days 1, 4, and 7 will be allowed at the investigator's discretion for patients who meet the criteria | |
Eligibility Criteria
Inclusion Criteria
- Refractory or relapsed (ie, bone marrow blasts >5%) CD33-positive AML.
- Age >=12 years.
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2.
- Initial peripheral white blood cells (WBC) counts >=30,000/mL; patients with a higher
WBC count should undergo cytoreduction.
- Adequate renal/hepatic functions
Exclusion Criteria
- Patients with prior treatment with gemtuzumab ozogamicin (GO).
- Patients with prior history of VOD/SOS.
- Prior HSCT is not allowed, if it was conducted within 2 months prior to study
enrollment.
- Patients with known active central nervous system (CNS) leukemia.
- Uncontrolled or active infectious status.
- Uncontrolled cardiac dysrhythmias of NCI CTCAE Grade 2, uncontrolled atrial
fibrillation of any grade.
- Sero-positivity to human immunodeficieny virus (HIV).
- Active hepatitis B or hepatitis C infection
- Chemotherapy, radiotherapy, or other anti-cancer therapy (except hydroxyurea as
cytoreduction) within 2 weeks prior to enrollment in the study.
- Major surgery within 4 weeks prior to enrollment.
- QTc interval >470 milliseconds (msec) using the Fridericia (QTcF), family or personal
history of long or short QT syndrome, Brugada syndrome or known history of QTc
prolongation, or Torsade de Pointes (TdP).
- The use of medications known to predispose to Torsades de Pointes within 2 weeks prior
to enrollment
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to gemtuzumab ozogamicin (GO).
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 12 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Corrected QTc interval change from baseline in ECG during Cycle 1-2 |
| Time Frame: | Immediately before and then at specified time points after GO administration of Cycle 1 Days 1, 4, and 7; Cycle 2 Days 1 and 7 (up to 2 cycles and each cycle is up to 43 days) |
| Safety Issue: | |
| Description: | Maximum change from baseline in corrected QT interval (QTc) [GO treatment 1-2 cycles. Cycle 1 ends up when the remission status is determined after recovery from blood cell counts. Cycle 2 starts after end of Cycle 1 or maximum 42 days after the last dose of GO in Cycle 1.] |
Secondary Outcome Measures
| Measure: | Clearance of total hP67.6 antibody, conjugated calicheamicin, and unconjugated calicheamicin in Liter/Hour |
| Time Frame: | Immediately before and then at specified time points after GO administration of Cycle 1 Days 1, 4, 7, 10, 15, and 21; Cycle 2 Days 1, 7, 15; and up to 36 days after the last dose of GO (up to 2 cycles, and each cycle is up to 43 days) |
| Safety Issue: | |
| Description: | Clearance of total hP67.6 antibody, conjugated calicheamicin, and unconjugated calicheamicin. [GO treatment 1-2 cycles. Cycle 1 ends up when the remission status is determined after recovery from blood cell counts. Cycle 2 starts after end of Cycle 1 or maximum 42 days after the last dose of GO in Cycle 1.] |
| Measure: | Volume of distribution of total hP67.6 antibody, conjugated calicheamicin, and unconjugated calicheamicin in Liter |
| Time Frame: | Immediately before and then at specified time points after GO administration of Cycle 1 Days 1, 4, 7, 10, 15, and 21; Cycle 2 Days 1, 7, 15; and up to 36 days after the last dose of GO (up to 2 cycles, and each cycle is up to 43 days) |
| Safety Issue: | |
| Description: | Volume of distribution of total hP67.6 antibody, conjugated calicheamicin, and unconjugated calicheamicin. [GO treatment 1-2 cycles. Cycle 1 ends up when the remission status is determined after recovery from blood cell counts. Cycle 2 starts after end of Cycle 1 or maximum 42 days after the last dose of GO in Cycle 1.] |
| Measure: | Rate of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.03 |
| Time Frame: | Until patient discontinues from study or as protocol specified up to 36 days after the last dose of GO or start of anticancer therapy, like consolidation and/or conditioning regimen, whichever occurs first (up to 2 cycles with each cycle up to 43 days) |
| Safety Issue: | |
| Description: | Adverse events (AEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE, version 4.03); VOD reported up to 1 year from enrollment. |
| Measure: | Rate of Participants With Abnormalities of Laboratory Tests as Assessed by CTCAE v4.03 |
| Time Frame: | Until patient discontinues from study or as protocol specified up to 36 days after the last dose of GO or start of anticancer therapy, like consolidation and/or conditioning regimen, whichever occurs first (up to 2 cycles with each cycle up to 43 days) |
| Safety Issue: | |
| Description: | Abnormalities of laboratory tests (hematology, chemistry, coagulation and urinalysis) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE, version 4.03) |
| Measure: | Incidence of the immunogenicity of anti-drug antibody (ADA)/neutralizing antibodies (NAb) |
| Time Frame: | Sample collection on Cycle 1 Days 1, 15, and 21; Cycle 2 Days 15, 21, and up to 36 days after the last dose of GO (up to 2 cycles, and each cycle is up to 43 days) |
| Safety Issue: | |
| Description: | Incidence of anti-drug antibody (ADA)/neutralizing antibodies (NAb).
Patients with ADA positive at the EOT visit (36 days after last dose) consists of visits approximately every 90 days until ADA titers are no longer detectable, return to baseline, stabilize at a level acceptable [GO treatment 1-2 cycles. Cycle 1 ends up when the remission status is determined after recovery from blood cell counts. Cycle 2 starts after end of Cycle 1 or maximum 42 days after the last dose of GO in Cycle 1.] |
| Measure: | Response rate of complete remission and complete remission with incomplete hematologic recovery |
| Time Frame: | Determination of remission status by blood and bone marrow aspiration (and biopsy if applicable) after recovery of blood counts is observed and/or at a maximum of 36 days after the last dose of GO treatment |
| Safety Issue: | |
| Description: | Response: complete remission (CR) and complete remission with incomplete hematologic recovery (CRi) by ELN 2017 criteria |
| Measure: | Overall survival in months |
| Time Frame: | Survival status will be collected for the study duration of 12 months from enrollment |
| Safety Issue: | |
| Description: | Survival status will be followed for all patients for the study duration. For any enrolled patient who may not be able to visit the study site at the protocol designated time, telephone contact is acceptable method for survival follow up, plus collecting cause(s) of death. |
Details
| Phase: | Phase 4 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Pfizer |
Trial Keywords
- gemtuzumab ozogamicin
- Mylotarg
- QT interval prolongation
- Pharmacokinetics
- Safety
- Veno-occlusive disease
- Anti-drug antibody
Last Updated
August 19, 2021
