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Evaluating QTc, PK, Safety of Gemtuzumab Ozogamicin (GO) in Patients With CD33+ R/R AML

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ClinicalTrials.gov Identifier: NCT03727750
Recruitment Status : Recruiting
First Posted : November 1, 2018
Last Update Posted : November 5, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
ECG Pharmacokinetics Safety Drug: Gemtuzumab Ozogamicin Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 56 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Single arm, open-label, interventional
Masking: None (Open Label)
Masking Description: open-label
Primary Purpose: Treatment
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
Actual Study Start Date : July 3, 2019
Estimated Primary Completion Date : June 6, 2022
Estimated Study Completion Date : June 6, 2022


Arm Intervention/treatment
Experimental: Gemtuzumab Ozogamicin (GO)
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
Drug: Gemtuzumab Ozogamicin
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 criteria




Primary Outcome Measures :
  1. 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) ]
    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 :
  1. 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) ]
    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.]

  2. 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) ]
    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.]

  3. 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) ]
    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.

  4. 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) ]
    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)

  5. 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) ]

    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.]


  6. 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 ]
    Response: complete remission (CR) and complete remission with incomplete hematologic recovery (CRi) by ELN 2017 criteria

  7. Overall survival in months [ Time Frame: Survival status will be collected for the study duration of 12 months from enrollment ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03727750


Contacts
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Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
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United States, Georgia
Augusta University Medical Center Clinical Research Pharmacy Not yet recruiting
Augusta, Georgia, United States, 30912
Georgia Cancer Center at Augusta University Not yet recruiting
Augusta, Georgia, United States, 30912
Canada, Alberta
Kaye Edmonton Clinic Recruiting
Edmonton, Alberta, Canada, T6G1Z1
University of Alberta Hospital Recruiting
Edmonton, Alberta, Canada, T6G2B7
Research Transition Facility Recruiting
Edmonton, Alberta, Canada, T6G2V2
Canada, Manitoba
Health Sciences Centre Not yet recruiting
Winnipeg, Manitoba, Canada, R3A 1R9
CancerCare Manitoba Not yet recruiting
Winnipeg, Manitoba, Canada, R3E 0V9
Hungary
Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet Not yet recruiting
Budapest, Hungary, 1097
Egyesitett Szent Istvan es Szent Laszlo Korhaz - Rendelointezet, Gyogyszertar Not yet recruiting
Budapest, Hungary, 1097
Debreceni Egyetem Klinikai Kozpont Belgyogyaszati Klinika Recruiting
Debrecen, Hungary, 4032
Petz Aladar Megyei Oktato Korhaz, Gyogyszereszeti Osztaly Not yet recruiting
Gyor, Hungary, 9024
Petz Aladar Megyei Oktato Korhaz, II. Belgyogyaszat - Hematologiai Osztaly Not yet recruiting
Gyor, Hungary, 9024
Somogy Megyei Kaposi Mor Oktato Korhaz Not yet recruiting
Kaposvar, Hungary, 7400
Poland
Apteka Szpitalna Uniwersyteckie Centrum Kliniczne Recruiting
Gdansk, Poland, 80-214
Klinika Hematologii i Transplantologii Recruiting
Gdansk, Poland, 80-214
Uniwersyteckie Centrum Kliniczne Recruiting
Gdansk, Poland, 80-214
Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku Recruiting
Wroclaw, Poland, 50-367
Pracownia Tomografii Komputerowej i Pracownia Rezonansu Magnetycznego Recruiting
Wroclaw, Poland, 50-369
Apteka Recruiting
Wroclaw, Poland, 50-556
United Kingdom
Belfast Health and Social Care Trust Not yet recruiting
Belfast, Antrim, United Kingdom, BT9 7AB
The Royal Bournemouth and Christchurch NHS Foundation Trust Not yet recruiting
Bournemouth, Dorset, United Kingdom, BH7 7DW
Taunton & Somerset NHS Foundation Trust Not yet recruiting
Taunton, Somerset, United Kingdom, TA1 5DA
Belfast Health and Social Care Trust Not yet recruiting
Belfast, United Kingdom, BT9 7AB
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03727750     History of Changes
Other Study ID Numbers: B1761031
2018-002619-89 ( EudraCT Number )
First Posted: November 1, 2018    Key Record Dates
Last Update Posted: November 5, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
gemtuzumab ozogamicin
Mylotarg
QT interval prolongation
Pharmacokinetics
Safety
Veno-occlusive disease
Anti-drug antibody
Additional relevant MeSH terms:
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Gemtuzumab
Antineoplastic Agents, Immunological
Antineoplastic Agents