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ASLAN003-003 is a multi-center, Phase IIA study to evalute the efficacy of ASLAN003 in AML patients who are ineligible for standard treatment with an expansion cohort in relapsed/refractory patients, and to determine the appropriate dose of ASLAN003 in combination with azacitidine in older (more than or equal to 60 years) AML patients who have exhausted any approved and available treatment options.
ASLAN003-003 is a multi-center, Phase IIA study to determine the optimum dose of ASLAN003 based on the safety, efficacy, and tolerability of varying doses of ASLAN003 (100 mg QD, 200 mg QD, 100 mg BID, and possibly 200 mg BID) administered to AML subjects daily for a continuous 28-day treatment cycle until disease relapse, disease progression, unacceptable toxicity, or withdrawal of consent.
The study has 2 parts and plans to enroll a total of 44 to 56 patients with 18 to 24 patients in Part 1 and 26 to 32 patients in Part 2 (comprising Parts 2A and 2B). The Overall Complete Remission Rate will be evaluated in AML patients not eligible for standard treatment (Part 1) and in relapsed and refractory AML patients (Part 2A) using the optimum dose of ASLAN003 established in Part 1 of the study. In Part 2B of the study, the appropriate dose of ASLAN003 in combination with azacitidine in older (more than or equal to 60 years) AML patients who have exhausted any approved and available treatment options will be determined.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: Dose Level 1 | Experimental |
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| Part 1: Dose Level 2 | Experimental |
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| Part 1: Dose Level 3 | Experimental |
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| Part 1: Dose Level 4 | Experimental |
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| Part 2:ASLAN003 at Optinum Dose Level -1 & Azacitidine | Experimental |
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| Part 2:ASLAN003 at Optinum Dose Level & Azacitidine | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ASLAN003 | Drug | Patients will be administered with the study drug, ASLAN003. The study drug is to be administered orally, QD or BID. It is recommended to administer the study drug with food or within 30 minutes after food intake. |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Complete Remission Rate | Defined as the proportion of patients with a best response of complete remission (CR) or complete remission with incomplete hematologic recovery (CRi), defined in accordance with the IWG Response Criteria in AML from day 29. Treatment failure is defined as not achieving any response 4 months after study treatment. IWG Response Criteria in AML defines CR or CRi as:
| 4 months after study treatment |
| Number of Participants With Adverse Events | Number of Participants with Adverse Events reported through 28 days post last study medication administration | Through 28 days post last study medication administration |
| Safety Assessments | Safety Assessments - Clinical laboratory test: Hematology and Chemistry | Through 28 days post last study medication administration |
| Measure | Description | Time Frame |
|---|---|---|
| Relapse Free Survival | Defined as the time the criteria for remission (CR or CRi) are first met until there is evidence of patient relapse, regardless of whether the patient is still taking study drug. Relapse is defined as:
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Inclusion Criteria:
Note: Patients who do not have sufficient archival BM aspiration sample and refuse to repeat the procedure may be enrolled in the trial only after written confirmation by ASLAN 5. Part 1: Patients who are ineligible for standard treatment of AML including to the following conditions:
Patients who are ineligible for chemotherapy, and have exhausted any approved and available treatment options. More details on patients who are considered as ineligible or unfit for chemotherapy as per Ferrara et al, Leukemia, 2013 can be found in Appendix 4.
Patients who have relapsed from prior remission;
Patients who have failed to respond to prior therapy including chemotherapy, hypomethylating agents, and bone marrow transplantation.
5. Part 2A: Patients who have relapsed or refractory AML to treatments including chemotherapy, hypomethylating agents, bone marrow transplantation, and other anti-leukemic agents
Relapsed patients who have bone marrow blasts ≥5%; or reappearance of blasts in the blood; or development of extramedullary disease after prior CR or CRi
Refractory patients who have no CR or CRi after 2 courses of intensive induction treatment 5. Part 2B: Older patients (more than or equal to 60 years) AML patients who have exhausted any approved and available treatment options.
6. Patients who have an ECOG performance status of ≤ 2 7. Patients with adequate renal and hepatic function, as defined below:
Estimated Glomerular Filtration Rate (eGFR) or creatinine clearance (CrCl) (CrCl calculated by the Cockroft and Gault method) ≥ 40 ml/min/1.73 m2
Total bilirubin, AST, and ALT ≤ 1.5 × ULN
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1 Site | Louisville | Kentucky | 40241 | United States | ||
| 1 Site |
An expansion cohort of 20 subjects in Part 2 was originally planned to be recruited to study the optimum dose selected by the Steering Committee. However, the study was terminated at the end of Cohort 4 due to Sponsor decision in July 2019 and did not proceed to Part 2 of the protocol. The primary and secondary endpoints were analyzed based on data from the 24 subjects in Part 1.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1: ASLAN003 100mg QD | ASLAN003: Patients will be administered with the study drug, ASLAN003. The study drug is to be administered orally, 100mg QD. Patients will receive a continuous 28-day treatment cycle of ASLAN003 at this dose until disease relapse, treatment failure (defined as failure to achieve a PR or higher within 4 cycles), development of unacceptable toxicity, withdrawal of consent or death. It is recommended to administer the study drug with food or within 30 minutes after food intake. |
| FG001 | Part 1: ASLAN003 200mg QD | ASLAN003: Patients will be administered with the study drug, ASLAN003. The study drug is to be administered orally, 200mg QD. Patients will receive a continuous 28-day treatment cycle of ASLAN003 at this dose until disease relapse, treatment failure (defined as failure to achieve a PR or higher within 4 cycles), development of unacceptable toxicity, withdrawal of consent or death. It is recommended to administer the study drug with food or within 30 minutes after food intake. |
| FG002 | Part 1: ASLAN003 100mg BID | ASLAN003: Patients will be administered with the study drug, ASLAN003. The study drug is to be administered orally, 100mg BID. Patients will receive a continuous 28-day treatment cycle of ASLAN003 at this dose until disease relapse, treatment failure (defined as failure to achieve a PR or higher within 4 cycles), development of unacceptable toxicity, withdrawal of consent or death. It is recommended to administer the study drug with food or within 30 minutes after food intake. |
| FG003 | Part 1: ASLAN003 200mg BID | ASLAN003: Patients will be administered with the study drug, ASLAN003. The study drug is to be administered orally, 200mg BID. Patients will receive a continuous 28-day treatment cycle of ASLAN003 at this dose until disease relapse, treatment failure (defined as failure to achieve a PR or higher within 4 cycles), development of unacceptable toxicity, withdrawal of consent or death. It is recommended to administer the study drug with food or within 30 minutes after food intake. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1: ASLAN003 100mg QD | ASLAN003: Patients will be administered with the study drug, ASLAN003. The study drug is to be administered orally, 100mg QD. Patients will receive a continuous 28-day treatment cycle of ASLAN003 at this dose until disease relapse, treatment failure (defined as failure to achieve a PR or higher within 4 cycles), development of unacceptable toxicity, withdrawal of consent or death. It is recommended to administer the study drug with food or within 30 minutes after food intake. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Overall Complete Remission Rate | Defined as the proportion of patients with a best response of complete remission (CR) or complete remission with incomplete hematologic recovery (CRi), defined in accordance with the IWG Response Criteria in AML from day 29. Treatment failure is defined as not achieving any response 4 months after study treatment. IWG Response Criteria in AML defines CR or CRi as:
| The primary efficacy endpoint was OCRR, defined as the proportion of subjects with a best response of CR or CRi. The "Measure Type" and data in the "Outcome Measure Data Table" is reported as "Count of Participants" and corresponding proportion is provided next to the count. Two subjects who had major protocol deviations were excluded from the Evaluable for Response (EFR) analysis set. Primary and secondary efficacy analyses were performed on the EFR set. | Posted | Count of Participants | Participants | 4 months after study treatment |
From the time of informed consent and until 28 days after the last administration of study drug, up to 24 months.
Definition of adverse event and/or serious adverse event, used to collect adverse event information, is the same with clinicaltrials.gov definition.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part 1: ASLAN003 100mg QD | ASLAN003: Patients will be administered with the study drug, ASLAN003. The study drug is to be administered orally, 100mg QD. Patients will receive a continuous 28-day treatment cycle of ASLAN003 at this dose until disease relapse, treatment failure (defined as failure to achieve a PR or higher within 4 cycles), development of unacceptable toxicity, withdrawal of consent or death. It is recommended to administer the study drug with food or within 30 minutes after food intake. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukocytosis | Blood and lymphatic system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | ASLAN Pharmaceuticals | +65 6222 4235 | contact@aslanpharma.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 31, 2018 | Jun 8, 2021 | Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 18, 2019 | Jun 8, 2021 | SAP_003.pdf |
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| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| From 12 weeks post end of treatment (EOT) until the date of first documented relapse or date of death from any cause, whichever came first, assessed up to 24 months |
| Clinical Benefit Rate | Defined as the proportion of subjects with an AML IWG best response of CR, CRi or PR. IWG Response Criteria in AML defines CR, CRi or PR as:
| 4 months after study treatment |
| % Change From Baseline in BM Blasts at Day 29 | Percent Change from Baseline in BM Blasts at Day 29 | Baseline and day 29 |
| Albury |
| New South Wales |
| Australia |
| 3 Sites | Darlinghurst | New South Wales | Australia |
| 1 Site | Waratah | New South Wales | Australia |
| 1 Site | Douglas | Queensland | Australia |
| 1 Site | Adelaide | South Australia | Australia |
| 3 Sites | Melbourne | Victoria | Australia |
| 3 Sites | Singapore | Singapore |
| Disease recurrence |
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| Lack of Efficacy |
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| Death |
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| Physician Decision |
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| Disease progression (n=4), study closed by sponsor (n=1) |
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| BG001 | Part 1: ASLAN003 200mg QD | ASLAN003: Patients will be administered with the study drug, ASLAN003. The study drug is to be administered orally, 200mg QD. Patients will receive a continuous 28-day treatment cycle of ASLAN003 at this dose until disease relapse, treatment failure (defined as failure to achieve a PR or higher within 4 cycles), development of unacceptable toxicity, withdrawal of consent or death. It is recommended to administer the study drug with food or within 30 minutes after food intake. |
| BG002 | Part 1: ASLAN003 100mg BID | ASLAN003: Patients will be administered with the study drug, ASLAN003. The study drug is to be administered orally, 100mg BID. Patients will receive a continuous 28-day treatment cycle of ASLAN003 at this dose until disease relapse, treatment failure (defined as failure to achieve a PR or higher within 4 cycles), development of unacceptable toxicity, withdrawal of consent or death. It is recommended to administer the study drug with food or within 30 minutes after food intake. |
| BG003 | Part 1: ASLAN003 200mg BID | ASLAN003: Patients will be administered with the study drug, ASLAN003. The study drug is to be administered orally, 200mg BID. Patients will receive a continuous 28-day treatment cycle of ASLAN003 at this dose until disease relapse, treatment failure (defined as failure to achieve a PR or higher within 4 cycles), development of unacceptable toxicity, withdrawal of consent or death. It is recommended to administer the study drug with food or within 30 minutes after food intake. |
| BG004 | Total | Total of all reporting groups |
| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Height | Mean | Standard Deviation | CM |
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| Weight | Mean | Standard Deviation | KG |
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| BMI | Mean | Standard Deviation | kg/m^2 |
|
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| Primary | Number of Participants With Adverse Events | Number of Participants with Adverse Events reported through 28 days post last study medication administration | Overview of Treatment Emergent Adverse Events (TEAEs) - Safety Population | Posted | Number | participants | Through 28 days post last study medication administration |
|
|
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| Primary | Safety Assessments | Safety Assessments - Clinical laboratory test: Hematology and Chemistry | The Outcome Measure Data includes number of analyzed subjects who had abnormal values for hematology and chemistry parameters and reported as AEs by the Investigators. All 24 (100%) subjects enrolled in the study were included in the safety population. | Posted | Number | participants | Through 28 days post last study medication administration |
|
|
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| Secondary | Relapse Free Survival | Defined as the time the criteria for remission (CR or CRi) are first met until there is evidence of patient relapse, regardless of whether the patient is still taking study drug. Relapse is defined as:
| All the subjects were non-responders in this study, relapse free survival was not evaluated. | Posted | From 12 weeks post end of treatment (EOT) until the date of first documented relapse or date of death from any cause, whichever came first, assessed up to 24 months |
|
|
| Secondary | Clinical Benefit Rate | Defined as the proportion of subjects with an AML IWG best response of CR, CRi or PR. IWG Response Criteria in AML defines CR, CRi or PR as:
| In addition to achieving no responses (CR or CRi) for the primary endpoint, no PRs were achieved either, thus CBR was not evaluated. | Posted | 4 months after study treatment |
|
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| Secondary | % Change From Baseline in BM Blasts at Day 29 | Percent Change from Baseline in BM Blasts at Day 29 | Only subjects with reduction of BM blasts evaluated on Day 29 are reported as % change from baseline in the Outcome Measure data. | Posted | Number | Percentage change | Baseline and day 29 |
|
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| 6 |
| 6 |
| 3 |
| 6 |
| 3 |
| 6 |
| EG001 | Part 1: ASLAN003 200mg QD | ASLAN003: Patients will be administered with the study drug, ASLAN003. The study drug is to be administered orally, 200mg QD. Patients will receive a continuous 28-day treatment cycle of ASLAN003 at this dose until disease relapse, treatment failure (defined as failure to achieve a PR or higher within 4 cycles), development of unacceptable toxicity, withdrawal of consent or death. It is recommended to administer the study drug with food or within 30 minutes after food intake. | 6 | 6 | 5 | 6 | 4 | 6 |
| EG002 | Part 1: ASLAN003 100mg BID | ASLAN003: Patients will be administered with the study drug, ASLAN003. The study drug is to be administered orally, 100mg BID. Patients will receive a continuous 28-day treatment cycle of ASLAN003 at this dose until disease relapse, treatment failure (defined as failure to achieve a PR or higher within 4 cycles), development of unacceptable toxicity, withdrawal of consent or death. It is recommended to administer the study drug with food or within 30 minutes after food intake. | 6 | 6 | 4 | 6 | 1 | 6 |
| EG003 | Part 1: ASLAN003 200mg BID | ASLAN003: Patients will be administered with the study drug, ASLAN003. The study drug is to be administered orally, 200mg BID. Patients will receive a continuous 28-day treatment cycle of ASLAN003 at this dose until disease relapse, treatment failure (defined as failure to achieve a PR or higher within 4 cycles), development of unacceptable toxicity, withdrawal of consent or death. It is recommended to administer the study drug with food or within 30 minutes after food intake. | 3 | 6 | 6 | 6 | 4 | 6 |
| Respiratory syncytial virus infection | Infections and infestations | Systematic Assessment |
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| Anal abscess | Infections and infestations | Systematic Assessment |
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| Lymph node abscess | Infections and infestations | Systematic Assessment |
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| Pathogen resistance | Infections and infestations | Systematic Assessment |
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| Pulmonary sepsis | Infections and infestations | Systematic Assessment |
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| Sepsis | Infections and infestations | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | Systematic Assessment |
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| Febrile neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Pyrexia | General disorders | Systematic Assessment |
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| Disease progression | General disorders | Systematic Assessment |
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| Fatigue | General disorders | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | Systematic Assessment |
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| Tumour lysis syndrome | Metabolism and nutrition disorders | Systematic Assessment |
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| Haematoma | Vascular disorders | Systematic Assessment |
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| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | Systematic Assessment |
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| Cholecystitis | Hepatobiliary disorders | Systematic Assessment |
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| Anaphylactic reaction | Immune system disorders | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | Systematic Assessment |
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| Decubitus ulcer | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Anaemia | Blood and lymphatic system disorders | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | Systematic Assessment |
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| Rash maculo-papular | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| Number of Patients with Any TEAE related to study treatment |
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| Number of Patients with Any TEAE CTCAE grade 3 or higher |
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| Number of Patients with Any TEAE CTCAE grade 3 or higher related to study treatment |
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| Number of Patients with Any TEAE with outcome of death |
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| Number of Patients with Any TEAE with outcome of death related to study treatment |
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| Number of Patients with Any serious TEAE |
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| Number of Patients with Any serious TEAE related to study treatment |
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| Number of Patients with Any TEAE leading to discontinuation of study therapy |
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| Number of Patients with Any TEAE leading to discontinuation of study therapy related to treatment |
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| Hematology - Abnormal/decreased hemoglobin values reported by Investigator as AEs of anaemia |
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| Hematology - Abnormal neutrophil count reported by Investigator as AE of neutropenia |
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| Hematology - Abnormal neutrophil counts reported by Investigator as AEs febrile neutropenia |
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| Hematology - Abnormal/decreased platelet count reported by Investigator as AEs of thrombocytopenia |
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| Chemistry - Abnormal serum potassium values reported by Investigator as AEs of hypokalaemia |
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| Chemistry - Elevated levels of serum glucose reported by Investigator as AEs of hyperglycaemia |
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| Chemistry - Abnormal blood creatinine reported by Investigator as AE of blood creatinine increased |
|