Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
CPX-351 · 9 trials · 10 indications
Overall survival was measured from the date of randomization to death from any cause, subjects not known to have died by the last follow-up were censored on the date they were last known to be alive.
Time-matched QTcF Changes From Baseline after the start of first infusion
The proportion of subjects surviving at 1 year was evaluated separately for each arm by the number of subjects alive at 1 year divided by the total number of subjects.
Response was defined according to International Working Group Criteria (Cheson, et al. 2003) which requires peripheral blood neutrophils of \>1000/µL and peripheral blood platelets of \>100,000/µL in the absence of bone marrow blasts.
Number of subjects with Dose Limiting toxicities will be used to determine the recommended phase II dose of CPX-351 to be used in the maintenance setting for newly diagnosed AML in complete remission.
To determine the safety, tolerability and toxicity of CPX-351 in the maintenance setting for newly diagnosed AML in complete remission by analyzing the incidence of treatment emergent adverse events reported.
The RP2D will be determined by the specified dose de-escalation/dose escalation algorithm.
The safety and tolerability of CPX-351 and targeted agents when given in combination, based on the incidence of adverse events (AEs) and dose limiting toxicities (DLTs)
The Recommended Phase 2 Dose (RP2D) as determined by an assessment of all safety data from the Dose Exploration Phase.
The safety and tolerability of CPX-351 and venetoclax when given in combination based on the incidence of AEs and DLTs
The key PK parameter AUCtau will be assessed
| Arm | Type | Description |
|---|---|---|
| Arm A (CPX-351) | EXPERIMENTAL | Subjects are eligible to receive up to 2 inductions and up to 2 consolidations with CPX-351. The number of inductions and consolidations a subject received depended on response. |
| Arm B (7+3) | ACTIVE_COMPARATOR | Subjects are eligible to receive up to 2 inductions and up to 2 consolidations with cytarabine and daunorubicin given as a 7 + 3, or 5 days of continuous infusion of cytarabine and 2 days of daunorubicin (5+2, second induction, consolidation courses) therapy. The number of inductions and consolidations a subject received depended on response. |
| CPX-351 | EXPERIMENTAL | Single Arm Study (Patients may receive up to 2 Inductions and 4 Consolidations): Induction 1: CPX-351 will be given intravenously at 100units/m2 on days 1, 3, and 5 over a 90 minute infusion. Induction 2: CPX-351 will be given intravenously at 100units/m2 on days 1 and 3 over a 90 minute infusion. Consolidations 1-4: CPX-351 will be given intravenously at 65units/m2 on days 1 and 3 over a 90 minute infusion. |
| CPX-351 (Arm A) | EXPERIMENTAL | First induction: 100 units/m2 on Days 1, 3, and 5 by 90-minute IV infusion Second induction: 100 units/m2 on Days 1 and 3 by 90-minute IV infusion Consolidation(s): 100 units/m2 on Days 1 and 3 by 90-minute IV infusion |
| Salvage Therapy (Arm B) | ACTIVE_COMPARATOR | First induction: Investigator's choice salvage therapy administered according to local practice Second induction: Investigator's choice salvage therapy administered according to local practice Consolidation(s): Investigator's choice consolidation therapy administered according to local practice |
| Arm A: CPX-351 | EXPERIMENTAL | First induction: CPX-351 at 100u/m2 administered on days 1, 3 and 5 Second induction: CPX-351 at 100u/m2 administered on days 1 and 3 Consolidation: CPX-351 at 100u/m2 administered on days 1 and 3 |
| Arm B: Cytarabine + Daunorubicin | ACTIVE_COMPARATOR | First induction: Cytarabine at a dose of 100mg/m2/day on days 1-7, Daunorubicin at dose of 45 or 60mg/m2 on days 1-3 Second induction: Cytarabine at a dose of 100mg/m2/day on days 1-5, Daunorubicin at a dose of 45 or 60 mg/m2/day on days 1 and 2 Consolidation: Investigator's Choice |
| Arm A | EXPERIMENTAL | - |
| Arm B | EXPERIMENTAL | - |
| Arm C | EXPERIMENTAL | - |
| CPX-351 and Venetoclax | EXPERIMENTAL | CPX-351 and Venetoclax will be administered over 28 day cycles |
| Cohort 1 | EXPERIMENTAL | Normal renal function |
| Cohort 2 | EXPERIMENTAL | Moderate renal impairment |
| Cohort 3 | EXPERIMENTAL | Severe renal impairment |
| Name | Type | Description |
|---|---|---|
| CPX-351 | DRUG | First induction: 100 units/m2 by 90-minute IV infusion on Days 1, 3, 5. Second induction: 100 units/m2 by 90-minute IV infusion on Days 1 and 3. Consolidation therapy: 65 units/m2 by 90-minute IV infusion on Days 1 and 3. |
| 7+3 (cytarabine and daunorubicin) | DRUG | First induction: 7+3 was administered as: cytarabine at a dose of 100 mg/m2/day on Days 1 through 7 by continuous infusion, and daunorubicin at a dose of 60 mg/m2/day on Days 1, 2, and 3. Second induction: 5+2 was administered as: cytarabine at a dose of 100 mg/m2/day on Days 1 through 5 by continuous infusion and daunorubicin at a dose of 60 mg/m2/day on Days 1 and 2. Consolidation therapy: 5+2 was administered as: cytarabine at a dose of 100 mg/m2/day on Days 1 through 5 by continuous infusion, and daunorubicin at a dose of 60 mg/m2/day on Days 1 and 2. |
| Intensive Salvage Therapy | DRUG | - |
| Cytarabine | DRUG | - |
| Daunorubicin | DRUG | - |
| Research skin biopsy | PROCEDURE | -And/or buccal swab * Pre-treatment * Post-induction (no earlier than Day 28 and no later than Day 56 from last induction) |
| Research blood draw | PROCEDURE | * Pre-treatment * Post-induction (no earlier than Day 28 and no later than Day 56 from last induction) * Post-consolidation 1 (if applicable) * Post-consolidation 2 (if applicable) * Post-transplant Day 30 (if applicable) * Post-transplant Day 100 (if applicable) |
| Research bone marrow aspirate | PROCEDURE | * Pre-treatment * Post-induction (no earlier than Day 28 and no later than Day 56 from last induction) * Post-consolidation 1 (if applicable) * Post-consolidation 2 (if applicable) * Post-transplant Day 30 (if applicable) * Post-transplant Day 100 (if applicable) |
| Venetoclax | DRUG | Will be administered over specified duration during induction and consolidation courses |
| Midostaurin | DRUG | Will be administered over specified duration during induction and consolidation courses |
| Enasidenib | DRUG | Will be administered over specified duration during induction and consolidation courses |
Inclusion Criteria: * Ability to understand and voluntarily give informed consent * Age 60-75 years at the time of diagnosis of AML * Pathological diagnosis of AML according to WHO criteria (with at least 20% blasts in the peripheral blood or bone marrow) * Confirmation of: * Therapy related AML...
CPX-351 is an investigational small molecule being studied for the treatment of Acute Myeloid Leukemia (AML), including high risk AML and AML in remission, as well as Myelodysplastic Syndromes and other hematologic malignancies. It is being developed by Jazz Pharmaceuticals plc (JAZZ) and is currently in Phase 2 clinical development.
CPX-351 is being developed by Jazz Pharmaceuticals plc, which trades on the stock exchange under the ticker JAZZ. The company is conducting clinical trials to evaluate the drug for the treatment of Acute Myeloid Leukemia and related hematologic conditions.
CPX-351 is currently in Phase 2 clinical development. It has completed four clinical trials, including two Phase 2 studies and two Phase 1 studies, with a total enrollment of 344 participants across all trials. The drug is investigational and has not been approved by regulatory authorities.
CPX-351 has been studied in four clinical trials. These include NCT00788892, a Phase 2 trial in newly diagnosed elderly AML patients; NCT00822094, a Phase 2 trial in adult patients with first relapse AML; NCT04038437, a Phase 1 trial combining CPX-351 with venetoclax; and NCT04075747, a Phase 1b master trial in previously untreated AML.
CPX-351 is also known by the brand name Vyxeos. It is a liposomal formulation of the chemotherapy drugs daunorubicin and cytarabine, developed by Jazz Pharmaceuticals. The drug is being investigated for the treatment of Acute Myeloid Leukemia and other hematologic malignancies.
CPX-351 is a liposomal encapsulation of daunorubicin and cytarabine, two chemotherapy agents that work by interfering with DNA synthesis in rapidly dividing cancer cells. The liposomal formulation is designed to deliver a synergistic ratio of the drugs to leukemia cells, potentially improving efficacy and reducing toxicity compared to standard chemotherapy.