3 ABNL-MARRO
Clinical trial protocol overview
Portocol Synopsis
OVERALL STUDY SCHEMATIC
PHASE 2 SCHEMATIC
SCHEDULE OF ASSESSMENTS FOR PHASE 1 (Arm A-ASTX727+Itacitinib)
SCHEDULE OF ASSESSMENTS FOR PHASE 2 (Arm A-ASTX727+Itacitinib)
SCHEDULE OF ASSESSMENTS FOR PHASE 2 (Arm B-ASTX727+ Ruxolitinib)
3.1 INTRODUCTION
3.1.1 Scientific Background
3.1.1.1 MDS/MPN
3.1.1.2 ASTX727
3.1.1.3 JAK/STAT pathway
3.1.1.4 Ruxolitinib
3.1.2 Pharmacology
3.1.3 Preclinical experience
3.1.3.1 ASTX727
3.1.3.2 Itacitinib
3.1.3.3 Ruxolitinib
3.1.4 Clinical Experience
3.1.4.1 ASTX727
3.1.4.2 Itacitinib
3.1.4.3 Ruxolitinib
- Need to fix the formatting (1.4.3)
3.1.5 Potential Risks and Benefits
3.1.5.1 ASTX727
3.1.5.2 Itacitinib
3.1.5.3 Ruxolitinib
3.1.6 Additional Safety Considerations
3.1.6.1 Drug-Drug Interactions (DDI)
- Need to add ruxolitinib (IB 5.1.5)
- 1.6.1
3.1.7 Study Rationale
3.2 STUDY OBJECTIVES
3.2.2 Secondary Objectives
3.2.3 Tertiary/exploratory Objectives
3.2.4 Primary Endpoints
3.2.5 Secondary Endpoints
3.2.6 Tertiary/Exploratory Endpoints
3.3 SUBJECT ELIGIBILITY
3.3.1 Study Popoulation
3.3.2 Inclusion Criteria
3.3.3 Exclusion Criteria
3.3.4 Inclusion of Underrepresented Populations
3.4 INVESTIGATIONAL PLAN
3.4.1 Study Design
3.4.1.1 Arm A: ASTX727 + Itacitinib
3.4.1.2 Arm B: ASTX727 + Ruxolitinib
3.4.2 Number of Patients
3.4.3 Study Enrollment
3.4.3.1 Registration
3.4.3.2 Screen Failures
3.4.3.3 Replacement of Patients Who Discontinue Early
3.4.4 Treatment Assignment
3.4.4.1 Randomization Method
3.4.5 Duration of Study Participation
3.4.6 Discontinuation of Treatment
3.4.6.1 Withdrawl from Study
3.4.7 Study Termination
3.4.8 End of Study
3.5 STUDY DRUGS
3.5.1 Description of Agents
3.5.1.1 ASTX727
3.5.1.2 Itacitinib
3.5.1.3 Ruxolitinib
3.5.2 Preparation and Dispensing
3.5.2.1 ASTX727
3.5.2.2 Itacitinib
3.5.2.3 Ruxolitinib
- I UPDATED from IB section 3.1
3.5.3 Packaging and Labeling
3.5.3.1 ASTX727
3.5.3.2 Itacitinib
3.5.3.3 Ruxolitinib
- I UPDATED it
3.5.4 Storage
3.5.4.1 ASTX727
3.5.4.2 Itacitinib
3.5.4.3 Ruxolitinib
3.5.5 Instruction to Subjects for Handling Study Drug
3.5.5.1 Treatment Comppliance
3.5.6 Drug Accountability and Compliance Check
3.6 TREATMENT OF SUBJECTS
3.6.1 Starting Doses and Schedules (Arm A- Phase 1B; Arm B-Phase 2)
- I updated the table (Table 6-1) to include both Arm A and Arm B
3.6.2 Dose Level Summary
3.6.3 Dose De-Escalation Pocedure (Phase 1)
3.6.3.1 Dose Limiting Toxicity
3.6.3.2 Recommended Phase 2 Dose and Schedule
3.6.3.3 Dose Recommendation for Arm B
3.6.4 Dose-Modification Guidleines
3.6.4.1 Treatment Interruption and Delays
3.6.4.2 Monitoring for Recovery of Adverse Events
3.6.4.4 Dosing Adjustment Guidelines for Non-Hematologic Adverse Events
3.6.5 Ruxolitinib Single Agent Dose Modification Guidelines
3.6.5.1 Dosing Modification Guidelines for Ruxolitinib Due to Hematologic Toxicity
3.6.5.2 Dose Modification Guidelines for Ruxolitinib Due to Nonhematologic Criteria
3.6.5.3 Dose Reduction of Ruxolitinib for Concomitant Usage of Inducer/Inhibitor of CYP3A4/5
3.6.6 Restricted and Prohibited Concomitant Medications and Procedures
3.6.6.1 Itactitinib + ASTX727
3.6.6.2 Ruxolitinib + ASTX727
- 6.6.2: I UPDATED this
3.6.7 Permittent Concomitant Medications and Procedures
3.6.8 Pregnancy Preacautions and Restrictions
3.7 STUDY ASSESSMENTS
3.7.1 Informed Consent
3.7.2 MDS/MPN Diagnosis
3.7.3 Screening
3.7.4 Physcial Examination
3.7.5 Height and Weight
3.7.6 Review of Concomitant Medications and Adverse Events
3.8 ADVERSE EVENTS
3.9 STATISTICAL AND QUANTITATIVE ANALYSES
3.10 ADMINISTRATIVE AND REGULATORY REQUIREMENTS
3.11 REFERENCES
- I need to update this!!
3.12 APPENDICES
3.12.1 Appendix 1: WHO Classification of MDS/MPN
3.12.2 Appendix 2: Eastern Cooperative Oncology Group (ECOG) Scale for Performance Status
3.12.3 Appendix 3: Modified Response Criteria for MDS/MPN Overlap Syndromes
3.12.4 Appendix 4: Myeloproliferative Neoplasm Symptom Assessment Form (MPN- SAF)
3.12.5 Appendix 5: Prohibited Concomitant Medications
3.12.6 Appendix 6: Excluded CYP3A4 Inducers and Inhibitors
3.12.7 Appendix 7: Drug-Drug Interaction of Ruxolitinib
- I udated this