Study of Carfilzomib in Combination With Induction Chemotherapy in Children With Relapsed or Refractory Acute Lymphoblastic Leukemia

Official Title

Phase 1b/2 Study of Carfilzomib in Combination With Induction Chemotherapy in Children With Relapsed or Refractory Acute Lymphoblastic Leukemia

Summary:

The purpose of Phase 1b of this study is to: - Asses the safety, tolerability and activity of carfilzomib, alone and in combination with induction chemotherapy, in children with relapsed or refractory acute lymphoblastic leukemia (ALL). - Determine the maximum tolerated dose (MTD) and to recommend a phase 2 dose of carfilzomib in combination with induction chemotherapy. The purpose of Phase 2 of this study is to compare the rate of complete response (CR) of carfilzomib in combination with vincristine, dexamethasone, PEG asparaginase, daunorubicin (VXLD) at the end of induction therapy to an appropriate external control.

Trial Description

Primary Outcome:

• Phase 1b: Number of Subjects who Experience One or More Adverse Events (AE)
• Phase 1b: Number of Subjects who Experience One or More Serious Adverse Events (SAEs)
• Phase 1b: Number of Subjects who Experienced a Clinically Significant Change from Baseline in Key Laboratory Analytes
• Phase 1b: Number of Subjects who Experience a Clinically Significant Change from Baseline in Vital Signs
• Phase 1b: Number of Subjects who Experience a Clinically Significant Change from Baseline in Physical Findings
• Phase 1b: Time to Toxicity
• Phase 1b: Maximum Tolerated Dose (MTD)
• Phase 2: Complete Response (CR) Rate After Induction Therapy in Subjects Aged ≥ 12 Months at Screening
• Phase 2: Complete Response (CR) Rate After Induction Therapy in Subjects Aged < 12 Months at Screening

• Phase 1b: Maximum plasma concentration (Cmax)
• Phase 1b: Total Plasma Exposure - Area Under the Curve (AUC)
• Phase 1b: Number of Subjects who Experience Complete Response (CR) or Complete Response with Incomplete Hematological Recovery (CRi)
• Phase 1b: Minimal Residual Disease (MRD) Status
• Phase 2: Number of Subjects who Experience a Treatment-emergent Adverse Event (TEAE)
• Phase 2: Number of Subjects who Experience a Treatment-related Adverse Event
• Phase 2: Number of Subjects who Experience a Severe Adverse Event
• Phase 2: Number of Subjects who Experience a Laboratory Abnormality
• Phase 2: Number of Subjects who Experience Complete Response (CR), Complete Response with Incomplete Recovery of Platelets (CRp), or Complete Response with Incomplete Hematological Recovery (CRi)
• Phase 2: Event Free Survival (EFS)
• Phase 2: Overall Survival (OS)
• Phase 2: Duration of Response (DOR)
• Phase 2: Minimal Residual Disease (MRD) Status in all Subjects
• Minimal Residual Disease (MRD) Status in Subjects with Complete Response (CR), CR with Incomplete Recovery of Platelets (CRp), CR with Partial Hematological Recovery (CRh) or CR with Incomplete Hematological Recovery (CRi)
• Number of Subjects who Experience a Stem Cell Transplant or Chimeric Antigen Receptor T Cell Therapy (CAR-T)
• Phase 2: Number of Subjects who Experience a Clinically Significant Change from Baseline in Laboratory Analytes
• Number of Subjects who Experience Complete Response (CR), CR with Incomplete Recovery of Platelets (CRp), or CR with Incomplete Hematological Recovery (CRi) After Consolidation Therapy in Subjects Aged ≥ 12 Months at Screening
• Number of Subjects who Experience Complete Response (CR), CR with Incomplete Recovery of Platelets (CRp), or CR with Incomplete Hematological Recovery (CRi) After Consolidation Therapy in Subjects Aged ≥ 12 Months at Screening
• Phase 2: Maximum Plasma Concentration (Cmax)
• Phase 2: Area Under the Concentration-time Curve (AUC)
• Phase 2: Half-life (t1/2) of Carfilzomib

View this trial on ClinicalTrials.gov