Trial Outcomes & Findings for A Study of CPX-351 (Vyxeos™) With Quizartinib for the Treatment of FLT3-ITD Mutation-Positive Acute Myeloid Leukemia (NCT NCT04209725)

Results Overview

Counting the number of patients with treatment related adverse events as a measure of safety and tolerability.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

1 participants

Primary outcome timeframe

Collected during treatment and for 30 days after last dose, approximately 35 total days for the 1 patient treated.

Results posted on

2023-12-05

Participant Flow

Participant milestones

Participant milestones
Measure	CPX-351 and Quizartinib Treatment Participants with FLT3 mutation positive AML will be given CPX-351 followed by quizartinib in three phases: induction, consolidation, and maintenance. CPX-351: To be given during the induction and consolidation phase and will consist of 44 mg/m\^2 daunorubicin with 100 mg/m\^2 cytarabine administered intravenously on Days 1, 3, and 5 during induction phase and Days 1 and 3 of consolidation phase. Quizartinib: To be given during induction, consolidation, and maintenance phases and will be taken orally at a dose of 30mg on Days 8-21 of induction phase, Days 6-21 of consolidation phase, and daily in maintenance phase.
Overall Study STARTED	1
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	CPX-351 and Quizartinib Treatment Participants with FLT3 mutation positive AML will be given CPX-351 followed by quizartinib in three phases: induction, consolidation, and maintenance. CPX-351: To be given during the induction and consolidation phase and will consist of 44 mg/m\^2 daunorubicin with 100 mg/m\^2 cytarabine administered intravenously on Days 1, 3, and 5 during induction phase and Days 1 and 3 of consolidation phase. Quizartinib: To be given during induction, consolidation, and maintenance phases and will be taken orally at a dose of 30mg on Days 8-21 of induction phase, Days 6-21 of consolidation phase, and daily in maintenance phase.
Overall Study Adverse Event	1

Baseline Characteristics

A Study of CPX-351 (Vyxeos™) With Quizartinib for the Treatment of FLT3-ITD Mutation-Positive Acute Myeloid Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CPX-351 and Quizartinib Treatment n=1 Participants Participants with FLT3 mutation positive AML will be given CPX-351 followed by quizartinib in three phases: induction, consolidation, and maintenance. CPX-351: To be given during the induction and consolidation phase and will consist of 44 mg/m\^2 daunorubicin with 100 mg/m\^2 cytarabine administered intravenously on Days 1, 3, and 5 during induction phase and Days 1 and 3 of consolidation phase. Quizartinib: To be given during induction, consolidation, and maintenance phases and will be taken orally at a dose of 30mg on Days 8-21 of induction phase, Days 6-21 of consolidation phase, and daily in maintenance phase.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	1 participants n=5 Participants

PRIMARY outcome

Timeframe: Collected during treatment and for 30 days after last dose, approximately 35 total days for the 1 patient treated.

Population: 1 patient was treated on study and did have treatment-related adverse events

Counting the number of patients with treatment related adverse events as a measure of safety and tolerability.

Outcome measures

Outcome measures
Measure	CPX-351 and Quizartinib Treatment n=1 Participants Participants with FLT3 mutation positive AML will be given CPX-351 followed by quizartinib in three phases: induction, consolidation, and maintenance. CPX-351: To be given during the induction and consolidation phase and will consist of 44 mg/m\^2 daunorubicin with 100 mg/m\^2 cytarabine administered intravenously on Days 1, 3, and 5 during induction phase and Days 1 and 3 of consolidation phase. Quizartinib: To be given during induction, consolidation, and maintenance phases and will be taken orally at a dose of 30mg on Days 8-21 of induction phase, Days 6-21 of consolidation phase, and daily in maintenance phase.
Number of Patients With Treatment Related Adverse Events After Taking CPX-351 and Quizartinib	1 Participants

PRIMARY outcome

Timeframe: from cycle 1 day 1 (each cycle is 28 days) until disease progression for up to 2 years post treatment

Population: Patients must have received at least one dose of CPX-351 or quizartinib, who have an adequate baseline disease assessment, and an adequate post-baseline assessment and who discontinue due to death or PD prior to their first assessment. The 1 patient that was enrolled discontinued study treatment in Cycle 1 prior to receiving Quizartinib, no post-baseline assessment was done. Therefore, no patients were analyzed.

Overall response is defined by the International Working Group response criteria (Cheson et al 2003) as having a complete remission (CR) - a complete morphologic response with complete blood count recovery absolute neutrophil count ≥1000/μL and platelet count ≥100,000/μL) or a complete morphologic response with an incomplete blood count recovery (CRi) - absolute neutrophil count \<1000/μL and/or platelet count \<100,000/μL)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from cycle 1 Day 1 (each cycle is 28 days) for up to 24 months

Population: The 1 patient that was enrolled discontinued study treatment in Cycle 1 prior to receiving Quizartinib, no post-baseline assessment was done. Therefore, no patients were analyzed.

Time to platelet recovery is defined as the time to when the peripheral blood platelet count is \>50, 000/ μL

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from Cycle 1 Day 1 (each cycle is 28 days) for up to 24 months

Population: The 1 patient that was enrolled discontinued study treatment in Cycle 1 prior to receiving Quizartinib, no post-baseline assessment was done. Therefore, no patients were analyzed.

Time to neutrophil recovery is defined as the time to when the peripheral blood ANC is ≥500/μL

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 60 days after consolidation therapy

Population: The patient discontinued treatment early and didn't follow induction and consolidation therapies to reach the alloHCT. Therefore no patients were analyzed.

Patients receiving allogeneic hematopoietic cell transplantation (alloHCT) following treatment in induction and consolidation therapies.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from diagnosis of relapse or refractory AML until disease progression for up to 2 years post treatment

Population: The 1 patient that was enrolled discontinued study treatment in Cycle 1 prior to receiving Quizartinib, no post-baseline evaluation was done. Therefore, no patients were analyzed.

Time to disease progression, confirmed by bone marrow biopsy.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from day 1 for up to 4 years

Population: The 1 patient that was enrolled discontinued study treatment in Cycle 1 prior to receiving Quizartinib. No post-baseline assessment was performed and was therefore censored at Date of First Treatment. Therefore, no patients were analyzed.

Defined as the number of days until evidence of PD by bone marrow biopsy/aspirate, or death, regardless of cause. Patients who are alive without a disease response assessment of relapsed disease will be censored at the last adequate disease assessment date. Patients without a disease response assessment will be censored at the first date of treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 8 months

Population: Only 1 patient was treated.

Overall survival is defined as the time from the first date of treatment until death as a result of any cause. For OS time, patients that have not died or are lost to follow-up will be censored at the date the patient was last known to be alive or the date of last contact.

Outcome measures

Outcome measures
Measure	CPX-351 and Quizartinib Treatment n=1 Participants Participants with FLT3 mutation positive AML will be given CPX-351 followed by quizartinib in three phases: induction, consolidation, and maintenance. CPX-351: To be given during the induction and consolidation phase and will consist of 44 mg/m\^2 daunorubicin with 100 mg/m\^2 cytarabine administered intravenously on Days 1, 3, and 5 during induction phase and Days 1 and 3 of consolidation phase. Quizartinib: To be given during induction, consolidation, and maintenance phases and will be taken orally at a dose of 30mg on Days 8-21 of induction phase, Days 6-21 of consolidation phase, and daily in maintenance phase.
Overall Survival (OS)	7.7 months

SECONDARY outcome

Timeframe: up to 4 years

Population: The 1 patient that was enrolled discontinued study treatment in Cycle 1 prior to receiving Quizartinib, no post-baseline assessment was done. Therefore, no patients were analyzed.

Late responses as defined by the International Working Group response criteria (Cheson et al 2003) as having a complete remission (CR) - a complete morphologic response with complete blood count recovery absolute neutrophil count ≥1000/μL and platelet count ≥100,000/μL) or a complete morphologic response with an incomplete blood count recovery (CRi) - absolute neutrophil count \<1000/μL and/or platelet count \<100,000/μL

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: approximately 3 months

Population: The patient discontinued treatment early and didn't follow induction and consolidation therapies to reach the alloHCT or maintenance therapy.

Patients who proceed through induction to next stages of consolidation and maintenance

Outcome measures

Outcome measures
Measure	CPX-351 and Quizartinib Treatment n=1 Participants Participants with FLT3 mutation positive AML will be given CPX-351 followed by quizartinib in three phases: induction, consolidation, and maintenance. CPX-351: To be given during the induction and consolidation phase and will consist of 44 mg/m\^2 daunorubicin with 100 mg/m\^2 cytarabine administered intravenously on Days 1, 3, and 5 during induction phase and Days 1 and 3 of consolidation phase. Quizartinib: To be given during induction, consolidation, and maintenance phases and will be taken orally at a dose of 30mg on Days 8-21 of induction phase, Days 6-21 of consolidation phase, and daily in maintenance phase.
Number of Patients Who Can Receive Consolidation and Maintenance Therapy	0 Participants

SECONDARY outcome

Timeframe: Observed during treatment and for 30 days after last dose, so approximately 35 days for the 1 patient treated.

Population: The 1 enrolled patient did not have a treatment-related death.

As determined by the number of treatment related deaths during study treatment

Outcome measures

Outcome measures
Measure	CPX-351 and Quizartinib Treatment n=1 Participants Participants with FLT3 mutation positive AML will be given CPX-351 followed by quizartinib in three phases: induction, consolidation, and maintenance. CPX-351: To be given during the induction and consolidation phase and will consist of 44 mg/m\^2 daunorubicin with 100 mg/m\^2 cytarabine administered intravenously on Days 1, 3, and 5 during induction phase and Days 1 and 3 of consolidation phase. Quizartinib: To be given during induction, consolidation, and maintenance phases and will be taken orally at a dose of 30mg on Days 8-21 of induction phase, Days 6-21 of consolidation phase, and daily in maintenance phase.
Treatment-related Mortality Rate	0 Participants

SECONDARY outcome

Timeframe: from cycle 1 day 1 (each cycle is 28 days) until disease progression for up to 2 years post treatment

Population: The 1 patient that was enrolled discontinued study treatment in Cycle 1 prior to receiving Quizartinib, no post-baseline assessment was done. Therefore, no patients were analyzed.

A PR is defined as persistent disease by morphology but with a \>50% reduction in the blast count/cellularity ratio compared to the most recent BM biopsy prior to treatment. A molecular complete remission is defined as no evidence of disease by bone marrow biopsy/aspirate by morphology, immunohistochemistry, or flow cytometry, and FLT3 mutation by MRD analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From Date of First Treatment to up to 2 years

Population: The 1 patient enrolled discontinued in Cycle 1. No post-baseline assessment therefore no patients analyzed

The mean time to achievement of a complete morphologic CR with persistent disease detected by flow or molecular minimal residual disease (MRD) analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From Date of First Treatment, up to 2 years

Population: The 1 patient enrolled discontinued the study prior to receiving their first dose of quizartinib. Therefore no patients analyzed.

Defined as the number of patients who received quizartinib and proceeded to alloHCT or DLI as part of this study and had treatment-related adverse events

Outcome measures

Outcome data not reported

Adverse Events

CPX-351 and Quizartinib Treatment

Serious events: 0 serious events

Other events: 1 other events

Deaths: 1 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	CPX-351 and Quizartinib Treatment n=1 participants at risk Participants with FLT3 mutation positive AML will be given CPX-351 followed by quizartinib in three phases: induction, consolidation, and maintenance. CPX-351: To be given during the induction and consolidation phase and will consist of 44 mg/m\^2 daunorubicin with 100 mg/m\^2 cytarabine administered intravenously on Days 1, 3, and 5 during induction phase and Days 1 and 3 of consolidation phase. Quizartinib: To be given during induction, consolidation, and maintenance phases and will be taken orally at a dose of 30mg on Days 8-21 of induction phase, Days 6-21 of consolidation phase, and daily in maintenance phase.
Blood and lymphatic system disorders Anaemia	100.0% 1/1 • Number of events 2 • Collected for 30 days after last dose, so approximately 35 days for the 1 patient treated. All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from day of first dose to 30 days after last protocol treatment and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Blood and lymphatic system disorders Febrile neutropenia	100.0% 1/1 • Number of events 1 • Collected for 30 days after last dose, so approximately 35 days for the 1 patient treated. All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from day of first dose to 30 days after last protocol treatment and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Blood and lymphatic system disorders Neutropenia	100.0% 1/1 • Number of events 2 • Collected for 30 days after last dose, so approximately 35 days for the 1 patient treated. All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from day of first dose to 30 days after last protocol treatment and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Blood and lymphatic system disorders Thrombocytopenia	100.0% 1/1 • Number of events 1 • Collected for 30 days after last dose, so approximately 35 days for the 1 patient treated. All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from day of first dose to 30 days after last protocol treatment and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Gastrointestinal disorders Diarrhoea	100.0% 1/1 • Number of events 1 • Collected for 30 days after last dose, so approximately 35 days for the 1 patient treated. All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from day of first dose to 30 days after last protocol treatment and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Metabolism and nutrition disorders Hypocalcaemia	100.0% 1/1 • Number of events 1 • Collected for 30 days after last dose, so approximately 35 days for the 1 patient treated. All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from day of first dose to 30 days after last protocol treatment and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
General disorders Chills	100.0% 1/1 • Number of events 1 • Collected for 30 days after last dose, so approximately 35 days for the 1 patient treated. All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from day of first dose to 30 days after last protocol treatment and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Investigations Electrocardiogram QT prolonged	100.0% 1/1 • Number of events 1 • Collected for 30 days after last dose, so approximately 35 days for the 1 patient treated. All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from day of first dose to 30 days after last protocol treatment and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Vascular disorders Orthostatic hypotension	100.0% 1/1 • Number of events 1 • Collected for 30 days after last dose, so approximately 35 days for the 1 patient treated. All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from day of first dose to 30 days after last protocol treatment and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Psychiatric disorders Insomnia	100.0% 1/1 • Number of events 1 • Collected for 30 days after last dose, so approximately 35 days for the 1 patient treated. All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from day of first dose to 30 days after last protocol treatment and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Gastrointestinal disorders Constipation	100.0% 1/1 • Number of events 1 • Collected for 30 days after last dose, so approximately 35 days for the 1 patient treated. All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from day of first dose to 30 days after last protocol treatment and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
General disorders Mucosal inflammation	100.0% 1/1 • Number of events 1 • Collected for 30 days after last dose, so approximately 35 days for the 1 patient treated. All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from day of first dose to 30 days after last protocol treatment and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Nervous system disorders Headache	100.0% 1/1 • Number of events 1 • Collected for 30 days after last dose, so approximately 35 days for the 1 patient treated. All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from day of first dose to 30 days after last protocol treatment and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Additional Information

Sarah Cannon Development Innovations, LLC

Phone: 844-710-6157

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60