Milademetan Plus Quizartinib Combination Study in FLT3-ITD Mutant Acute Myeloid Leukemia (AML)
Study Details
Study Description
Brief Summary
Participants with AML that have gone into remission and come back (relapsed) or gone into remission with a number of leukemia cells still in their system (refractory) will be recruited for this study. They will also be positive for FLT3-ITD mutation.
Participants will receive a combined dose of quizartinib and milademetan that have not been approved by the US Food and Drug Administration yet (m).
The combination of these drugs will be provided in different amounts on defined days (dosing schedules).
It is expected that the combination of milademetan and quizartinib will be safe and well tolerated. It is expected that the combination may fight the leukemia better than a single drug.
The study will run for approximately 3 years. There may be up to 156 participants.
The study has 2 parts:
-
Part 1 will test 24-36 participants in approximately 15 study centers globally. Participants will receive two study drugs (milademetan and quizartinib) in different amounts on specific days. Information will be gathered to see what dosing schedule of the drug combination is best (maximum tolerated/recommended dose).
-
Part 2 of the study will confirm the recommended dosing schedule identified in Part 1 is effective. A larger number of participants will receive the recommended dose in approximately 15 additional sites worldwide as necessary, based on the enrollment rate, the population, and the standard of care available to them at the time of enrollment.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1 - Quizartinib + Milademetan Participants with relapsed/refractory FLT3-ITD Mutant AML receive quizartinib + milademetan at increasing and/or decreasing doses and schedules |
Drug: Quizartinib
20 or 30 mg tablets for oral administration
Other Names:
Drug: Milademetan
5, 20, 80 or 200 mg capsules for oral administration
Other Names:
|
| Experimental: Part 2 - Cohort 1 Participants with relapsed/refractory FLT3-ITD Mutant AML receive the recommended dose of quizartinib + milademetan determined by Part 1 |
Drug: Quizartinib
20 or 30 mg tablets for oral administration
Other Names:
Drug: Milademetan
5, 20, 80 or 200 mg capsules for oral administration; 30, 45, 80, or 100 mg capsules may be utilized
Other Names:
|
| Experimental: Part 2 - Cohort 2 Participants with newly diagnosed FLT3-ITD Mutant AML unfit for chemotherapy receive the recommended dose of quizartinib + milademetan determined by Part 1 |
Drug: Quizartinib
20 or 30 mg tablets for oral administration
Other Names:
Drug: Milademetan
5, 20, 80 or 200 mg capsules for oral administration; 30, 45, 80, or 100 mg capsules may be utilized
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Dose Limiting Toxicities (DLTs) Following Administration of Milademetan in Combination With Quizartinib [Baseline up to 28 days (Cycle 1) from the start of study drug administration]
A dose limiting toxicity (DLT) is defined as any non-hematological treatment-emergent adverse event (TEAE) unless incontrovertibly related to disease progression, intercurrent illness, or concomitant medication, that occurs during the DLT evaluation period (28 days) in each dose level cohort, and is Grade 3 or higher according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, with exceptions specified: Grade 3 or higher aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels, OR elevation in total bilirubin ≥3.0 × upper limit of normal (ULN) that does not return to ≤Grade 2 elevation within 7 days. Absolute neutrophil count (ANC) <0.5 × 10^9/L, platelets <20 × 10^9/L, and marrow cellularity <5% at 6 weeks or later from start of therapy without any evidence of leukemia.
- Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib [Baseline up to 35 days after last dose of study drug, up to approximately 2 years 3 months]
A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during the treatment period (from date of first dose up to 35 days after the last dose of the study treatment), having been absent at pretreatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment related to the pretreatment state, when the AE is continuous. AEs collected after 35 days after the last dose of study drug were not considered TEAEs unless they were treatment-related.
Secondary Outcome Measures
- Number of Participants With Best Overall Response Following Administration of Milademetan in Combination With Quizartinib [Baseline up to first documented response, disease progression, withdrawal, or death (whichever occurs first), up to approximately 2 years 3 months]
Based on European LeukemiaNet criteria, complete remission (CR) was bone marrow (BM) blasts <5%, absence of circulating blasts/blasts with Auer rods, absence of extramedullary disease (EMD), absolute neutrophil count (ANC) ≥1.0×10^9/L, and platelet count ≥100×10^9/L; CR with Incomplete Blood Count Recovery (CRi): all CR criteria except for residual neutropenia or thrombocytopenia; Morphologic Leukemia Free State (MLFS): BM blasts <5%, absence of blasts with Auer rods, absence of EMD, and no hematologic recovery required; Partial Remission (PR): decrease of BM blast percentage by at least 50% (to 5% to 25%) and all criteria of CR; Stable disease: absence of CR, CRi, MLFS, or PR, and criteria for progressive disease (PD) not met; Relapse (after CR/CRi): BM blasts ≥5%, or reappearance of leukemic blasts, or EMD development; and PD: increase in BM blast % and/or increase of absolute blast counts: >50% increase in marrow blasts over baseline, >50% increase in peripheral blasts, or new EMD.
- Overall Response Rate Following Administration of Milademetan in Combination With Quizartinib [Baseline up to first documented response, disease progression, withdrawal, or death (whichever occurs first), up to approximately 2 years 3 months]
Overall response rate was defined as the number of participants with composite Complete Remission (CRc)+Morphological Leukemia Free State (MLFS)+Partial Remission (PR) based on the European LeukemiaNet criteria. Based on the European LeukemiaNet criteria, CRc was defined as complete remission (CR) as bone marrow (BM) blasts <5%, absence of circulating blasts/blasts with Auer rods, absence of extramedullary disease (EMD), absolute neutrophil count (ANC) ≥1.0×10^9/L, and platelet count ≥100×10^9/L; CR with Incomplete Blood Count Recovery (CRi): all CR criteria except for residual neutropenia or thrombocytopenia; Morphologic Leukemia Free State (MLFS): BM blasts <5%, absence of blasts with Auer rods, absence of EMD, and no hematologic recovery required; Partial Remission (PR): decrease of BM blast percentage by at least 50% (to 5% to 25%) and all criteria of CR.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Has reached ≥18 years old or the age of the age of majority in their country
-
Part 1 (dose escalation): Has FLT3-ITD mutant (≥ 3% FLT3-ITD/total FLT3) AML (primary AML, secondary, or therapy-related AML), and has treatment failure to prior AML therapy or have relapsed after prior AML therapy
-
Part 2 (dose expansion): Has FLT3-ITD mutant (≥3% FLT3-ITD/total FLT3) AML (primary, secondary, or therapy-related AML), and has treatment failure to prior AML therapy or have relapsed after prior AML therapy, OR has newly diagnosed AML who are ineligible for intensive induction chemotherapy
-
Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (or 3 for patients with newly diagnosed AML between 18 and 74 years old)
-
Has protocol-defined adequate renal, hepatic and cardiac status
-
Is not pregnant, and if not postmenopausal or a surgically sterile male or female, is willing to use a highly effective contraceptive method upon enrollment, during the course of the study, and for 6 months following the last dose of investigational drug
-
Is able and willing to provide protocol-defined bone marrow biopsies/aspirates
Exclusion Criteria:
-
Has central nervous system (CNS) involvement of leukemia - patients with a history of CNS leukemia may be eligible if the CNS leukemia is adequately controlled (defined as no clinical symptoms of CNS disease and at least 2 consecutive lumbar punctures with no evidence of disease prior to study enrollment) after discussion and approval from the Sponsor
-
Has acute promyelocytic leukemia (AML subtype M3)
-
Has uncontrolled or significant cardiovascular disease or QTc interval >450 ms (average of triplicate determination)
-
Has an uncontrolled infection requiring intravenous antibiotics, antivirals, or antifungals.
-
Has known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection based on positive tests during Screening
-
Has persistent, clinically significant > Grade 1 non-hematologic toxicity from prior AML therapies
-
Has any history or medical condition, metastatic condition, drug/medication use or other condition that might, per protocol or in the opinion of the investigator, compromise:
-
safety or well-being of the participant or offspring
-
safety of study staff
-
analysis of results
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ronald Reagan Medical Center, UCLA | Los Angeles | California | United States | 90095 |
| 2 | Yale Cancer Center | New Haven | Connecticut | United States | 06510 |
| 3 | University of Kansas Cancer Center | Fairway | Kansas | United States | 66205 |
| 4 | Rogel Cancer Center, University of Michigan | Ann Arbor | Michigan | United States | 48109 |
| 5 | Roswell Park Comprehensive Cancer Center | Buffalo | New York | United States | 14263 |
| 6 | Duke University Cancer Center | Durham | North Carolina | United States | 27710 |
| 7 | Sidney Kimmel Cancer Center, Thomas Jefferson University | Philadelphia | Pennsylvania | United States | 19107 |
| 8 | MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Daiichi Sankyo, Inc.
Investigators
- Study Director: Clinical Team Leader, Daiichi Sankyo, Inc.
Study Documents (Full-Text)
More Information
Publications
None provided.- DS3032-A-U105
Study Results
Participant Flow
| Recruitment Details | A total of 10 out of the 22 screened participants who met all inclusion criteria and no exclusion criteria were enrolled in the study at 8 clinic sites in the United States. Only Part 1 is reported since the study terminated prior to Part 2. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Part 1, Cohort 1: Quizartinib + Milademetan | Part 1, Cohort 1A: Quizartinib + Milademetan |
|---|---|---|
| Arm/Group Description | Participants with relapsed/refractory FLT3-ITD Mutant AML who received milademetan 90 mg daily (QD) Day 1 - Day 14 and quizartinib 30 mg QD. | Participants with relapsed/refractory FLT3-ITD Mutant AML who received milademetan 90 mg daily (QD) Day 1 - Day 7 and quizartinib 30 mg QD. |
| Period Title: Overall Study | ||
| STARTED | 4 | 6 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 4 | 6 |
Baseline Characteristics
| Arm/Group Title | Part 1, Cohort 1: Quizartinib + Milademetan | Part 1, Cohort 1A: Quizartinib + Milademetan | Total |
|---|---|---|---|
| Arm/Group Description | Participants with relapsed/refractory FLT3-ITD Mutant AML who received milademetan 90 mg daily (QD) Day 1 - Day 14 and quizartinib 30 mg QD. | Participants with relapsed/refractory FLT3-ITD Mutant AML who received milademetan 90 mg daily (QD) Day 1 - Day 7 and quizartinib 30 mg QD. | Total of all reporting groups |
| Overall Participants | 4 | 6 | 10 |
| Age (years) [Median (Full Range) ] | |||
| Median (Full Range) [years] |
64
|
65
|
64
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
0
0%
|
2
33.3%
|
2
20%
|
| Male |
4
100%
|
4
66.7%
|
8
80%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
| White |
4
100%
|
5
83.3%
|
9
90%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
1
16.7%
|
1
10%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
4
100%
|
6
100%
|
10
100%
|
Outcome Measures
| Title | Number of Participants With Dose Limiting Toxicities (DLTs) Following Administration of Milademetan in Combination With Quizartinib |
|---|---|
| Description | A dose limiting toxicity (DLT) is defined as any non-hematological treatment-emergent adverse event (TEAE) unless incontrovertibly related to disease progression, intercurrent illness, or concomitant medication, that occurs during the DLT evaluation period (28 days) in each dose level cohort, and is Grade 3 or higher according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, with exceptions specified: Grade 3 or higher aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels, OR elevation in total bilirubin ≥3.0 × upper limit of normal (ULN) that does not return to ≤Grade 2 elevation within 7 days. Absolute neutrophil count (ANC) <0.5 × 10^9/L, platelets <20 × 10^9/L, and marrow cellularity <5% at 6 weeks or later from start of therapy without any evidence of leukemia. |
| Time Frame | Baseline up to 28 days (Cycle 1) from the start of study drug administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| Dose-limiting toxicities were assessed in the DLT Evaluable Set. |
| Arm/Group Title | Part 1, Cohort 1: Quizartinib + Milademetan | Part 1, Cohort 1A: Quizartinib + Milademetan |
|---|---|---|
| Arm/Group Description | Participants with relapsed/refractory FLT3-ITD Mutant AML who received milademetan 90 mg daily (QD) Day 1 - Day 14 and quizartinib 30 mg QD. | Participants with relapsed/refractory FLT3-ITD Mutant AML who received milademetan 90 mg daily (QD) Day 1 - Day 7 and quizartinib 30 mg QD. |
| Measure Participants | 2 | 6 |
| Count of Participants [Participants] |
1
25%
|
0
0%
|
| Title | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib |
|---|---|
| Description | A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during the treatment period (from date of first dose up to 35 days after the last dose of the study treatment), having been absent at pretreatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment related to the pretreatment state, when the AE is continuous. AEs collected after 35 days after the last dose of study drug were not considered TEAEs unless they were treatment-related. |
| Time Frame | Baseline up to 35 days after last dose of study drug, up to approximately 2 years 3 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treatment-emergent adverse events (irrespective of causality) were assessed in the Safety Analysis Set. |
| Arm/Group Title | Part 1, Cohort 1: Quizartinib + Milademetan | Part 1, Cohort 1A: Quizartinib + Milademetan |
|---|---|---|
| Arm/Group Description | Participants with relapsed/refractory FLT3-ITD Mutant AML who received milademetan 90 mg daily (QD) Day 1 - Day 14 and quizartinib 30 mg QD. | Participants with relapsed/refractory FLT3-ITD Mutant AML who received milademetan 90 mg daily (QD) Day 1 - Day 7 and quizartinib 30 mg QD. |
| Measure Participants | 4 | 6 |
| Any TEAEs |
4
100%
|
6
100%
|
| Any Blood and Lymphatic System Disorders |
2
50%
|
5
83.3%
|
| Any Cardiac Disorders |
1
25%
|
2
33.3%
|
| Any Ear and Labyrinth Disorders |
1
25%
|
1
16.7%
|
| Any Eye Disorders |
2
50%
|
0
0%
|
| Any Gastrointestinal Disorders |
4
100%
|
6
100%
|
| Any General Disorders and Administration Site Conditions |
3
75%
|
5
83.3%
|
| Any Immune System Disorders |
1
25%
|
0
0%
|
| Any Infections and Infestations |
4
100%
|
1
16.7%
|
| Any Injury, Poisoning and Procedural Complications |
0
0%
|
3
50%
|
| Any Investigations |
3
75%
|
5
83.3%
|
| Any Metabolism and Nutrition Disorders |
4
100%
|
5
83.3%
|
| Any Musculoskeletal and Connective Tissue Disorders |
2
50%
|
4
66.7%
|
| Any Nervous System Disorders |
4
100%
|
3
50%
|
| Any Psychiatric Disorders |
2
50%
|
2
33.3%
|
| Any Renal and Urinary Disorders |
1
25%
|
2
33.3%
|
| Any Respiratory, Thoracic, and Mediastinal Disorders |
4
100%
|
4
66.7%
|
| Any Skin and Subcutaneous Tissue Disorders |
3
75%
|
5
83.3%
|
| Any Vascular Disorders |
3
75%
|
1
16.7%
|
| Title | Number of Participants With Best Overall Response Following Administration of Milademetan in Combination With Quizartinib |
|---|---|
| Description | Based on European LeukemiaNet criteria, complete remission (CR) was bone marrow (BM) blasts <5%, absence of circulating blasts/blasts with Auer rods, absence of extramedullary disease (EMD), absolute neutrophil count (ANC) ≥1.0×10^9/L, and platelet count ≥100×10^9/L; CR with Incomplete Blood Count Recovery (CRi): all CR criteria except for residual neutropenia or thrombocytopenia; Morphologic Leukemia Free State (MLFS): BM blasts <5%, absence of blasts with Auer rods, absence of EMD, and no hematologic recovery required; Partial Remission (PR): decrease of BM blast percentage by at least 50% (to 5% to 25%) and all criteria of CR; Stable disease: absence of CR, CRi, MLFS, or PR, and criteria for progressive disease (PD) not met; Relapse (after CR/CRi): BM blasts ≥5%, or reappearance of leukemic blasts, or EMD development; and PD: increase in BM blast % and/or increase of absolute blast counts: >50% increase in marrow blasts over baseline, >50% increase in peripheral blasts, or new EMD. |
| Time Frame | Baseline up to first documented response, disease progression, withdrawal, or death (whichever occurs first), up to approximately 2 years 3 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Best Overall Response was assessed in the Full Analysis Set. |
| Arm/Group Title | Part 1, Cohort 1: Quizartinib + Milademetan | Part 1, Cohort 1A: Quizartinib + Milademetan |
|---|---|---|
| Arm/Group Description | Participants with relapsed/refractory FLT3-ITD Mutant AML who received milademetan 90 mg daily (QD) Day 1 - Day 14 and quizartinib 30 mg QD. | Participants with relapsed/refractory FLT3-ITD Mutant AML who received milademetan 90 mg daily (QD) Day 1 - Day 7 and quizartinib 30 mg QD. |
| Measure Participants | 4 | 6 |
| Complete remission (CR) |
0
0%
|
0
0%
|
| Complete Remission with Partial Hematological Recovery (CRh) |
0
0%
|
0
0%
|
| Complete Remission with Incomplete Blood Count Recovery (CRi) |
1
25%
|
3
50%
|
| Morphologic Leukemia Free State (MLFS) |
0
0%
|
0
0%
|
| Partial Remission (PR) |
0
0%
|
0
0%
|
| Stable Disease (SD) |
1
25%
|
2
33.3%
|
| Relapse |
0
0%
|
0
0%
|
| Missing |
2
50%
|
1
16.7%
|
| Title | Overall Response Rate Following Administration of Milademetan in Combination With Quizartinib |
|---|---|
| Description | Overall response rate was defined as the number of participants with composite Complete Remission (CRc)+Morphological Leukemia Free State (MLFS)+Partial Remission (PR) based on the European LeukemiaNet criteria. Based on the European LeukemiaNet criteria, CRc was defined as complete remission (CR) as bone marrow (BM) blasts <5%, absence of circulating blasts/blasts with Auer rods, absence of extramedullary disease (EMD), absolute neutrophil count (ANC) ≥1.0×10^9/L, and platelet count ≥100×10^9/L; CR with Incomplete Blood Count Recovery (CRi): all CR criteria except for residual neutropenia or thrombocytopenia; Morphologic Leukemia Free State (MLFS): BM blasts <5%, absence of blasts with Auer rods, absence of EMD, and no hematologic recovery required; Partial Remission (PR): decrease of BM blast percentage by at least 50% (to 5% to 25%) and all criteria of CR. |
| Time Frame | Baseline up to first documented response, disease progression, withdrawal, or death (whichever occurs first), up to approximately 2 years 3 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall response rate was assessed in the Full Analysis Set. |
| Arm/Group Title | Part 1, Cohort 1: Quizartinib + Milademetan | Part 1, Cohort 1A: Quizartinib + Milademetan |
|---|---|---|
| Arm/Group Description | Participants with relapsed/refractory FLT3-ITD Mutant AML who received milademetan 90 mg daily (QD) Day 1 - Day 14 and quizartinib 30 mg QD. | Participants with relapsed/refractory FLT3-ITD Mutant AML who received milademetan 90 mg daily (QD) Day 1 - Day 7 and quizartinib 30 mg QD. |
| Measure Participants | 4 | 6 |
| Count of Participants [Participants] |
1
25%
|
3
50%
|
Adverse Events
| Time Frame | Treatment-emergent adverse events (TEAEs) were collected from date of first dose up to 35 days after last dose of study drug, up to approximately 2 years 3 months. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | A TEAE is defined as an adverse event (AE) that emerges during the treatment period (from date of first dose up to 35 days after the last dose of the study treatment), having been absent at pretreatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment related to the pretreatment state, when the AE is continuous. | |||
| Arm/Group Title | Part 1, Cohort 1: Quizartinib + Milademetan | Part 1, Cohort 1A: Quizartinib + Milademetan | ||
| Arm/Group Description | Participants with relapsed/refractory FLT3-ITD Mutant AML who received milademetan 90 mg daily (QD) Day 1 - Day 14 and quizartinib 30 mg QD. | Participants with relapsed/refractory FLT3-ITD Mutant AML who received milademetan 90 mg daily (QD) Day 1 - Day 7 and quizartinib 30 mg QD. | ||
All Cause Mortality |
||||
| Part 1, Cohort 1: Quizartinib + Milademetan | Part 1, Cohort 1A: Quizartinib + Milademetan | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/4 (75%) | 1/6 (16.7%) | ||
Serious Adverse Events |
||||
| Part 1, Cohort 1: Quizartinib + Milademetan | Part 1, Cohort 1A: Quizartinib + Milademetan | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/4 (100%) | 3/6 (50%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 1/4 (25%) | 0/6 (0%) | ||
| Febrile neutropenia | 1/4 (25%) | 0/6 (0%) | ||
| Thrombocytopenia | 1/4 (25%) | 0/6 (0%) | ||
| Cardiac disorders | ||||
| Bradycardia | 1/4 (25%) | 0/6 (0%) | ||
| Gastrointestinal disorders | ||||
| Small intestinal obstruction | 0/4 (0%) | 1/6 (16.7%) | ||
| Vomiting | 0/4 (0%) | 1/6 (16.7%) | ||
| General disorders | ||||
| Disease progression | 0/4 (0%) | 1/6 (16.7%) | ||
| Infections and infestations | ||||
| Arthritis infective | 1/4 (25%) | 0/6 (0%) | ||
| Pneumonia | 0/4 (0%) | 1/6 (16.7%) | ||
| Sepsis | 1/4 (25%) | 0/6 (0%) | ||
| Septic shock | 1/4 (25%) | 0/6 (0%) | ||
| Sinusitis fungal | 1/4 (25%) | 0/6 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Subdural haemorrhage | 0/4 (0%) | 1/6 (16.7%) | ||
| Metabolism and nutrition disorders | ||||
| Fluid overload | 0/4 (0%) | 1/6 (16.7%) | ||
| Nervous system disorders | ||||
| Syncope | 0/4 (0%) | 1/6 (16.7%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Hypoxia | 1/4 (25%) | 1/6 (16.7%) | ||
| Vascular disorders | ||||
| Haematoma | 1/4 (25%) | 0/6 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Part 1, Cohort 1: Quizartinib + Milademetan | Part 1, Cohort 1A: Quizartinib + Milademetan | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/4 (100%) | 6/6 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 1/4 (25%) | 3/6 (50%) | ||
| Febrile neutropenia | 2/4 (50%) | 1/6 (16.7%) | ||
| Neutropenia | 1/4 (25%) | 2/6 (33.3%) | ||
| Thrombocytopenia | 1/4 (25%) | 1/6 (16.7%) | ||
| Cardiac disorders | ||||
| Atrial fibrillation | 1/4 (25%) | 0/6 (0%) | ||
| Bradycardia | 1/4 (25%) | 0/6 (0%) | ||
| Cardiac failure | 0/4 (0%) | 1/6 (16.7%) | ||
| Sinus bradycardia | 0/4 (0%) | 1/6 (16.7%) | ||
| Tachycardia | 1/4 (25%) | 0/6 (0%) | ||
| Ear and labyrinth disorders | ||||
| Ear pain | 1/4 (25%) | 0/6 (0%) | ||
| Hypoacusis | 0/4 (0%) | 1/6 (16.7%) | ||
| Middle ear effusion | 1/4 (25%) | 0/6 (0%) | ||
| Eye disorders | ||||
| Photophobia | 1/4 (25%) | 0/6 (0%) | ||
| Retinal exudates | 1/4 (25%) | 0/6 (0%) | ||
| Vision blurred | 1/4 (25%) | 0/6 (0%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 0/4 (0%) | 1/6 (16.7%) | ||
| Abdominal pain lower | 1/4 (25%) | 0/6 (0%) | ||
| Anal incontinence | 1/4 (25%) | 1/6 (16.7%) | ||
| Diarrhoea | 2/4 (50%) | 4/6 (66.7%) | ||
| Dry mouth | 0/4 (0%) | 2/6 (33.3%) | ||
| Dyspepsia | 1/4 (25%) | 1/6 (16.7%) | ||
| Mouth ulceration | 0/4 (0%) | 1/6 (16.7%) | ||
| Nausea | 2/4 (50%) | 4/6 (66.7%) | ||
| Oesophagitis | 0/4 (0%) | 1/6 (16.7%) | ||
| Oral pain | 0/4 (0%) | 1/6 (16.7%) | ||
| Retching | 1/4 (25%) | 0/6 (0%) | ||
| Small intestinal obstruction | 0/4 (0%) | 1/6 (16.7%) | ||
| Upper gastrointestinal haemorrhage | 1/4 (25%) | 0/6 (0%) | ||
| Vomiting | 2/4 (50%) | 3/6 (50%) | ||
| General disorders | ||||
| Asthenia | 0/4 (0%) | 1/6 (16.7%) | ||
| Chest discomfort | 1/4 (25%) | 0/6 (0%) | ||
| Chills | 2/4 (50%) | 0/6 (0%) | ||
| Disease progression | 0/4 (0%) | 1/6 (16.7%) | ||
| Fatigue | 1/4 (25%) | 4/6 (66.7%) | ||
| Generalised oedema | 1/4 (25%) | 0/6 (0%) | ||
| Oedema peripheral | 1/4 (25%) | 1/6 (16.7%) | ||
| Pyrexia | 2/4 (50%) | 1/6 (16.7%) | ||
| Swelling face | 1/4 (25%) | 0/6 (0%) | ||
| Immune system disorders | ||||
| Hypersensitivity | 1/4 (25%) | 0/6 (0%) | ||
| Infections and infestations | ||||
| Arthritis infective | 1/4 (25%) | 0/6 (0%) | ||
| Clostridium difficile colitis | 1/4 (25%) | 0/6 (0%) | ||
| Ear infection | 1/4 (25%) | 0/6 (0%) | ||
| Oesophageal candidiasis | 1/4 (25%) | 0/6 (0%) | ||
| Oral candidiasis | 1/4 (25%) | 0/6 (0%) | ||
| Pharyngitis | 1/4 (25%) | 0/6 (0%) | ||
| Pneumonia | 2/4 (50%) | 1/6 (16.7%) | ||
| Sepsis | 1/4 (25%) | 0/6 (0%) | ||
| Septic shock | 1/4 (25%) | 0/6 (0%) | ||
| Sinusitis fungal | 1/4 (25%) | 0/6 (0%) | ||
| Upper respiratory tract infection | 1/4 (25%) | 0/6 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Contusion | 0/4 (0%) | 1/6 (16.7%) | ||
| Fall | 0/4 (0%) | 1/6 (16.7%) | ||
| Ligament sprain | 0/4 (0%) | 1/6 (16.7%) | ||
| Limb injury | 0/4 (0%) | 1/6 (16.7%) | ||
| Procedural pain | 0/4 (0%) | 1/6 (16.7%) | ||
| Subdural haemorrhage | 0/4 (0%) | 1/6 (16.7%) | ||
| Investigations | ||||
| Activated partial thromboplastin time prolonged | 0/4 (0%) | 1/6 (16.7%) | ||
| Alanine aminotransferase increased | 0/4 (0%) | 2/6 (33.3%) | ||
| Blood alkaline phosphatase increased | 0/4 (0%) | 1/6 (16.7%) | ||
| Blood creatinine increased | 1/4 (25%) | 2/6 (33.3%) | ||
| Blood fibrinogen decreased | 0/4 (0%) | 1/6 (16.7%) | ||
| C-reactive protein increased | 0/4 (0%) | 2/6 (33.3%) | ||
| Electrocardiogram QT prolonged | 0/4 (0%) | 2/6 (33.3%) | ||
| Fibrin D dimer increased | 0/4 (0%) | 1/6 (16.7%) | ||
| Gamma-glutamyltransferase increased | 0/4 (0%) | 1/6 (16.7%) | ||
| Heart rate decreased | 1/4 (25%) | 0/6 (0%) | ||
| Lymphocyte count decreased | 0/4 (0%) | 1/6 (16.7%) | ||
| Neutrophil count decreased | 0/4 (0%) | 1/6 (16.7%) | ||
| Platelet count decreased | 0/4 (0%) | 2/6 (33.3%) | ||
| Urine output decreased | 1/4 (25%) | 0/6 (0%) | ||
| White blood cell count decreased | 1/4 (25%) | 2/6 (33.3%) | ||
| Metabolism and nutrition disorders | ||||
| Acidosis | 1/4 (25%) | 0/6 (0%) | ||
| Decreased appetite | 2/4 (50%) | 4/6 (66.7%) | ||
| Dehydration | 0/4 (0%) | 1/6 (16.7%) | ||
| Fluid overload | 1/4 (25%) | 2/6 (33.3%) | ||
| Hyperglycaemia | 0/4 (0%) | 1/6 (16.7%) | ||
| Hypermagnesaemia | 1/4 (25%) | 0/6 (0%) | ||
| Hypernatraemia | 1/4 (25%) | 0/6 (0%) | ||
| Hyperphosphataemia | 0/4 (0%) | 1/6 (16.7%) | ||
| Hyperuricaemia | 0/4 (0%) | 1/6 (16.7%) | ||
| Hypervolaemia | 1/4 (25%) | 0/6 (0%) | ||
| Hypoalbuminaemia | 2/4 (50%) | 2/6 (33.3%) | ||
| Hypocalcaemia | 1/4 (25%) | 3/6 (50%) | ||
| Hypokalaemia | 2/4 (50%) | 4/6 (66.7%) | ||
| Hypomagnesaemia | 3/4 (75%) | 2/6 (33.3%) | ||
| Hyponatraemia | 0/4 (0%) | 2/6 (33.3%) | ||
| Hypophosphataemia | 1/4 (25%) | 2/6 (33.3%) | ||
| Zinc deficiency | 0/4 (0%) | 1/6 (16.7%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 2/4 (50%) | 1/6 (16.7%) | ||
| Back pain | 1/4 (25%) | 1/6 (16.7%) | ||
| Bone pain | 1/4 (25%) | 1/6 (16.7%) | ||
| Joint swelling | 1/4 (25%) | 0/6 (0%) | ||
| Muscular weakness | 0/4 (0%) | 1/6 (16.7%) | ||
| Musculoskeletal pain | 1/4 (25%) | 1/6 (16.7%) | ||
| Myalgia | 0/4 (0%) | 2/6 (33.3%) | ||
| Neck pain | 1/4 (25%) | 1/6 (16.7%) | ||
| Pain in extremity | 2/4 (50%) | 0/6 (0%) | ||
| Nervous system disorders | ||||
| Balance disorder | 0/4 (0%) | 1/6 (16.7%) | ||
| Dizziness | 0/4 (0%) | 1/6 (16.7%) | ||
| Facial paralysis | 0/4 (0%) | 1/6 (16.7%) | ||
| Headache | 1/4 (25%) | 2/6 (33.3%) | ||
| Hypoaesthesia | 2/4 (50%) | 0/6 (0%) | ||
| Lethargy | 0/4 (0%) | 2/6 (33.3%) | ||
| Memory impairment | 0/4 (0%) | 2/6 (33.3%) | ||
| Presyncope | 1/4 (25%) | 0/6 (0%) | ||
| Syncope | 0/4 (0%) | 1/6 (16.7%) | ||
| Tremor | 0/4 (0%) | 1/6 (16.7%) | ||
| Psychiatric disorders | ||||
| Confusional state | 0/4 (0%) | 1/6 (16.7%) | ||
| Irritability | 0/4 (0%) | 1/6 (16.7%) | ||
| Mental status changes | 1/4 (25%) | 0/6 (0%) | ||
| Phonophobia | 1/4 (25%) | 0/6 (0%) | ||
| Renal and urinary disorders | ||||
| Acute kidney injury | 1/4 (25%) | 1/6 (16.7%) | ||
| Pollakiuria | 0/4 (0%) | 1/6 (16.7%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 3/4 (75%) | 2/6 (33.3%) | ||
| Dysphonia | 1/4 (25%) | 0/6 (0%) | ||
| Dyspnoea | 2/4 (50%) | 2/6 (33.3%) | ||
| Epistaxis | 1/4 (25%) | 1/6 (16.7%) | ||
| Hypoxia | 1/4 (25%) | 1/6 (16.7%) | ||
| Nasal congestion | 1/4 (25%) | 1/6 (16.7%) | ||
| Oropharyngeal pain | 2/4 (50%) | 0/6 (0%) | ||
| Pleural effusion | 0/4 (0%) | 1/6 (16.7%) | ||
| Pulmonary hypertension | 0/4 (0%) | 1/6 (16.7%) | ||
| Respiratory failure | 1/4 (25%) | 0/6 (0%) | ||
| Rhinitis allergic | 0/4 (0%) | 1/6 (16.7%) | ||
| Wheezing | 1/4 (25%) | 0/6 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Decubitus ulcer | 1/4 (25%) | 0/6 (0%) | ||
| Hyperhidrosis | 1/4 (25%) | 1/6 (16.7%) | ||
| Night sweats | 1/4 (25%) | 1/6 (16.7%) | ||
| Petechiae | 0/4 (0%) | 2/6 (33.3%) | ||
| Pruritus | 0/4 (0%) | 1/6 (16.7%) | ||
| Purpura | 0/4 (0%) | 1/6 (16.7%) | ||
| Rash | 0/4 (0%) | 1/6 (16.7%) | ||
| Rash erythematous | 1/4 (25%) | 0/6 (0%) | ||
| Rash maculo-papular | 1/4 (25%) | 1/6 (16.7%) | ||
| Vascular disorders | ||||
| Deep vein thrombosis | 1/4 (25%) | 0/6 (0%) | ||
| Haematoma | 1/4 (25%) | 0/6 (0%) | ||
| Hypertension | 0/4 (0%) | 1/6 (16.7%) | ||
| Hypotension | 1/4 (25%) | 0/6 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Contact for Clinical Trial Disclosure Information |
|---|---|
| Organization | Daiichi Sankyo |
| Phone | 908-992-6400 |
| CTRinfo@dsi.com |
- DS3032-A-U105