Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication VYXEOS is indicated for the treatment of newly diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) in adults and pediatric patients 1 year and older. VYXEOS is a liposomal combination of daunorubicin, an anthracycline topoisomerase inhibitor, and cytarabine, a nucleoside metabolic inhibitor, that is indicated for the treatment of newly diagnosed… FDA label
Also known as Vyxeos, JZP351, Vyxeos liposomal, Liposome-encapsulated Daunorubicin-Cytarabine, Cytarabine-Daunorubicin Liposome for Injection, Liposomal AraC-Daunorubicin CPX-351, Liposomal Cytarabine-Daunorubicin
CPX-351 · 15 trials · 19 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.
This is defined as the percentage of subjects with event-free survival (EFS) at 6 months. EFS is defined as the number of months where patients are in a remission state.
Defined by the International Working Group Criteria. Will be summarized using frequencies and relative frequencies.
Defined as time from entering the relevant randomisation to the relevant question until death from any cause. Patients who are alive at the end of the trial or have been lost to follow up will be censored at their date last seen. For randomisations 2 and 3 this outcome will also be calculated as time from transplantation in order to run a sensitivity analysis.
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.
To establish the recommended phase 2 dose of Vyxeos®/CPX-351 in combination with clofarabine in children with relapsed/refractory AML
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 |
|---|---|---|
| Standard arm | ACTIVE_COMPARATOR | - |
| Investigational arm | EXPERIMENTAL | - |
| 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 and Glasdegib | EXPERIMENTAL | In Induction, subjects receive 44mg/m2/100mg/m2 IV on days 1, 3 and 5 and Glasdegib 100mg PO daily on days 6 to 28. If re-induction is needed: Subjects receive 44mg/m2/100mg/m2 IV on days 1 and 3 and Glasdegib 100mg PO daily on days 4 to 28. In consolidation: Subjects receive 29mg/m2/65mg/m2 IV on days 1 and 3 and Glasdegib 100mg PO daily on days 4 to 28. If maintenance is required, Subjects receive Glasdegib 100mg PO daily for up to one year |
| Treatment (CPX-351) | EXPERIMENTAL | INDUCTION: Patients receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity. RE-INDUCTION: Patients who do not achieve remission receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Beginning 5-8 weeks after the start of the last induction, patients who achieve CR receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3. Treatment repeats every 45 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. |
| R1: Intermediate dose Cytarabine | ACTIVE_COMPARATOR | First Randomisation (closed to recruitment) - control arm: Intermediate dose Cytarabine (1g/m\^2 administered by intravenous infusion over 2 hours on days 1-5 inclusive) |
| R1: Vyxeos | EXPERIMENTAL | First Randomisation (closed to recruitment) - experimental arm: Vyxeos (29mg/65mg/m\^2 administered by intravenous infusion over 90 minutes on days 1 and 3) |
| R2: FB4 | ACTIVE_COMPARATOR | Second Randomisation - under 55 years - control arm: Fludarabine (40mg/m\^2 days -7, -6, -5, and -4), Busulphan (3.2mg/kg days -7, -6, -5 and -4) |
| R2: TBF | EXPERIMENTAL | Second Randomisation - under 55 years - experimental arm: Thiotepa (5mg/kg day -7 and -6), Busulphan (3.2mg/kg days -5, -4 and -3), Fludarabine (50mg/m\^2 days -5, -4 and -3) |
| R3: FB2 | ACTIVE_COMPARATOR | Third Randomisation - 55 years and over (or under 55 with comorbidities) - control arm: Fludarabine (30mg/m\^2 days -6, -5, -4, -3 and -2), Busulphan (3.2mg/kg days -6 and -5) |
| Mini-TBF | EXPERIMENTAL | Third Randomisation - 55 years and over (or under 55 with comorbidities) - experimental arm: Thiotepa (5mg/kg day -6), Busulphan (3.2mg/kg days -5 and -4), Fludarabine (50mg/m\^2 days -5, -4, and -3) |
| 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 |
| Treatment with Vyxeos®/CPX-351 in combination with clofarabine | EXPERIMENTAL | Treatment will consist of 2 courses. An adapted regimen is used to combine Vyxeos®/CPX-351 at a fixed dose given at day 1, 3, 5 with clofarabine at the allocated dose level given at day 2-6 in course one, and only Vyxeos®/CPX-351 in course 2. A maximum of 3 dose levels of clofarabine are expected to be tested in this study. |
| 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 |
|---|---|---|
| Cytarabine | DRUG | Induction therapy: 200 mg/m2 i.v. (continuously) d1-7 Consolidation therapy: * Patients age 18-60 years o Intermediate-dose cytarabine 1500 mg/m2 i.v. q12h (3 hrs) d1-3 * Patients age \>60 years o Intermediate-dose cytarabine 1000 mg/m2 i.v. q12h (3 hrs) d1-3 |
| Daunorubicin | DRUG | Induction therapy: 60 mg/m2 i.v. (1 hr) d1-3 |
| CPX-351 | DRUG | Induction 1: o CPX-351 44 mg/m2 daunorubicin / 100 mg/m2 cytarabine \[100 U/m²\] i.v. (90 min) d1,3,5 Induction 2: o CPX-351 44 mg/m2 daunorubicin / 100 mg/m2 cytarabine \[100 U/m²\] i.v. (90 min) d1,3 Consolidation therapy: o CPX-351 29 mg/m2 daunorubicin / 65 mg/m2 cytarabine \[65 U/m²\] i.v. (90 min) d1,3 |
| 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. |
| Cytarabine and Idarubicin | DRUG | Induction 1: Cytarabine 200 mg/m2 i.v. (continuously) d1-7 + Idarubicin 12mg/m2 d1, 2, 3 i.v (60 min) Induction 2: Cytarabine 1500 mg/m2 i.v. q12h d1-3 Consolidation: Cytarabine 1500 mg/m2 i.v. q12h d1-3 |
| CPX-315 | DRUG | Induction 1:CPX-351 44 mg/m2 daunorubicin / 100 mg/m2 cytarabine i.v. (90 min) d1,3,5 Induction 2: CPX-351 44 mg/m2 daunorubicin / 100 mg/m2 cytarabine i.v. (90 min) d1,3 Consolidation therapy:CPX-351 29 mg/m2 daunorubicin / 65 mg/m2 cytarabine i.v. (90 min) d1,3 |
| Glasdegib | DRUG | Given PO |
| Liposome-encapsulated Daunorubicin-Cytarabine | DRUG | Given IV |
| Vyxeos | DRUG | Vyxeos administered by intravenous infusion |
| Fludarabine | DRUG | Fludarabine administered by intravenous infusion |
| Busulphan | DRUG | Busulphan administered by intravenous infusion |
| Thiotepa | DRUG | Thiotepa administered by intravenous infusion |
| Intensive Salvage Therapy | DRUG | - |
| Vyxeos 44 MG / 100 MG Liposome Injection | DRUG | Vyxeos®/CPX-351 will be infused in 90 minutes on day 1, 3 and 5 only, 3 hours after the end of clofarabine (if administered on the same day). |
| Clofarabine | DRUG | Clofarabine infusion will be given according to the assigned dose level, over 2 hours IV, daily on day 2-6 (for 5 consecutive days). |
| 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 |
Patient Inclusion Criteria: 1. Patients with newly diagnosed AML and intermediate- or adverse-risk genetics (according to 2017 ELN criteria \[Appendix B\]), including AML with myelodysplasia-related changes (AML-MRC) and therapy-related AML according to the World Health Organization (WHO) classific...
CPX-351 is used to treat acute myeloid leukemia (AML) and related blood cancers, including high risk AML, AML that has returned after treatment, therapy-related AML, and AML with myelodysplasia-related changes. It is also being studied for relapse prevention in patients whose AML is in remission and for myelodysplastic syndromes.
CPX-351 is developed by Jazz Pharmaceuticals plc, which trades on the Nasdaq under the ticker JAZZ. Jazz Pharmaceuticals is the company behind the drug's clinical development program across acute myeloid leukemia and related hematologic malignancies.
CPX-351 is in clinical development, with Phase 2 studies among its ongoing and completed trials. It is an investigational small molecule and has not been established as approved for the indications listed here. Its trial program spans Phase 1 and Phase 2 studies in acute myeloid leukemia and related conditions.
CPX-351 has been studied in six clinical trials. The recruiting study is NCT04990102, a Phase 1/2 trial of CPX-351 for relapse prevention in AML in remission. Other trials include NCT04231851 with glasdegib, NCT04075747 in previously untreated AML, and NCT04038437 with venetoclax.
CPX-351 is a small molecule therapeutic developed for acute myeloid leukemia and related hematologic malignancies. It is designed as a fixed-ratio combination formulation, pairing two chemotherapy agents in a defined ratio to act together against leukemic cells. Its clinical program evaluates it both as a single agent and in combination with other drugs.
Across six clinical trials, CPX-351 has enrolled a total of 1,252 patients. Five of those trials are completed and one is currently recruiting. The studies enroll adults aged 18 years and older and have been conducted in the United States.