Testing the Combination of Standard Induction Therapy With Gemtuzumab Ozogamicin and Midostaurin as a Novel Approach to Treating Patients With Newly Diagnosed FLT-3 Mutated Acute Myeloid Leukemia
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|ClinicalTrials.gov Identifier: NCT03900949|
Recruitment Status : Recruiting
First Posted : April 3, 2019
Last Update Posted : April 4, 2019
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia||Drug: Daunorubicin Drug: Cytarabine Biological: Gemtuzumab Ozogamicin Drug: Midostaurin||Phase 1|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||28 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study to Evaluate the Safety and Preliminary Efficacy of Gemtuzumab Ozogamicin and Midostaurin When Used in Combination With Standard Cytarabine and Daunorubicin Induction for Newly Diagnosed FLT3-mutated AML.|
|Actual Study Start Date :||March 21, 2019|
|Estimated Primary Completion Date :||January 1, 2023|
|Estimated Study Completion Date :||January 1, 2025|
Participants receive one or two induction chemotherapy cycles, followed by one or two consolidation therapy cycles.
Induction includes daunorubicin (IV) days 1, 2, 3 at either 60 mg/m2 (Dose Levels 1, 2, 3) or 90 mg/m2 (Dose Level 4); cytarabine (IV) given days 1 through 7 (100 mg/m2) for 1-3 hours; ozogamuzumab ozogamicin (IV) (days 1, 4, 7), followed by midostaurin (oral) taken twice daily on Days 8 through 21. Induction may be repeated once.
Consolidation 1 consists of a 28 day cycle with high dose cytarabine (IV) (3 g/m2) given every 12 hours on Days 1, 3, and 5, with gemtuzumab ozogamicin (IV) given on Day 1, followed by midostaurin (50 mg, oral) taken twice daily on Days 8 through 21.
Consolidation 2 consists of a 28 day cycle with high dose cytarabine (IV) (3 g/m2) given every 12 hours on Days 1, 3, and 5, followed by midostaurin (50 mg, oral) taken twice daily on Days 8 through 21.
Anthrocycline component of the standard induction 7+3 chemotherapy regimen for treatment of AML.
Component of standard 7+3 chemotherapy regimen for treatment of AML.
Other Name: ara-C
Biological: Gemtuzumab Ozogamicin
Anti-CD33 monoclonal antibody given during induction at different dose levels.
Other Name: Mylotarg
An oral multi-kinase inhibitor with effects against FLT3, given through induction and consolidation.
Other Name: Rydapt
- Dose limiting toxicity during first treatment cycle [ Time Frame: 42 days after start of therapy ]A dose limiting toxicity (DLT) during the first treatment cycle, which is defined as: 1) any Grade 3+ non-hematological toxicity based on NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0. and additional protocol-defined criteria; 2) a hematologic toxicity defined as: failure to recover ANC > 500/μL or platelet count > 50,000/μL (by 6 weeks after first induction or re-induction) in participants with < 5% blasts in the bone marrow, absence of myelodysplastic changes, and/or absence of evidence of disease (i.e., flow cytometry of bone marrow).
- Incidents of serious adverse events [ Time Frame: 90 days after last day of study treatment or until participant receives alternative AML treatment ]Incidence and type of serious adverse events (SAEs) based on the NCI CTCAE v5.0
- Incidence of 30-day mortality [ Time Frame: 30 days after start of initial induction ]30 day mortality
- Rate of complete composite remission (CCR) [ Time Frame: End of consolidation treatment (up to 120 days) ]Complete composite remission is defined as meeting criteria for complete remission (CR), complete remission with incomplete blood count recovery (CRi), or complete remission with incomplete platelet recovery (CRp).
- Objective response rate (ORR) [ Time Frame: End of consolidation treatment (up to 120 days) ]ORR is defined as the sum of CR, CRi, Morphologic leukemia-free state (MLFS), and Partial remission (PR)
- Event free survival (EFS) [ Time Frame: Date of primary refractory disease, relapse, or death from any cause (up to 24 months following end of treatment) ]EFS will be measured from start of on-study therapy (i.e., Day 1) to the date of primary refractory disease, relapse from CR or CRi, or death from any cause. Participants not known to have failed induction therapy, relapsed, or died at time of last follow-up will be censored on the date they were last examined (i.e., 2 years following completion of on-study therapy)
- Duration of response (DoR) [ Time Frame: Date of documented relapse (up to 24 months following end of treatment) ]For only participants that achieve CR or CRi, the DoR is measured from the date of first documented response (CR, CRi) until the date of relapse. Participants not known to have relapsed at time of last follow-up will be censored on the date they were last examined (i.e., 2 years following completion of on-study therapy).
- Relapse free survival (RFS) [ Time Frame: Date of relapse or death from any cause (up to 24 months following end of treatment) ]For only participants that achieve CR or CRi, RFS will be measured from the date of first documented response (CR, CRi) to the date of relapse or death from any cause. Participants not known to have relapsed or died at time of last follow-up will be censored on the date they were last examined (i.e., 2 years following completion of on-study therapy).
- Overall survival (OS) [ Time Frame: Date of death (up to 24 months following end of treatment) ]Survival
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): NCT03900949
|Contact: Uma Borate, MDfirstname.lastname@example.org|
|Contact: Basak Gokcoraemail@example.com|
|United States, Oregon|
|OHSU Knight Cancer Institute||Recruiting|
|Portland, Oregon, United States, 97239|
|Contact: Uma Borate, MD 503-494-5058 firstname.lastname@example.org|