Subscribe

Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive:

Phase 2 Study of CPX-351 plus Venetoclax in Patients with Acute Myeloid Leukemia

2020 Year in Review - AML - Leukemia

Based on findings that showed the addition of the BCL-2 inhibitor venetoclax to hypomethylating agents (HMAs) improved overall response rates (ORRs) and overall survival (OS) compared with HMAs alone, a study was designed to investigate the safety and efficacy of venetoclax combined with CPX-351, a fixed-dose liposomal formulation of daunorubicin and cytarabine, in patients with acute myeloid leukemia (AML).

The dose of CPX-351 was constant and consisted of daunorubicin 44 mg/m2 plus cytarabine 100 mg/m2 intravenously on days 1, 3, and 5 during induction and daunorubicin 29 mg/m2 plus cytarabine 65 mg/m2 intravenously on days 1 and 3 during consolidation. The safety lead-in cohort consisted of patients with relapsed or refractory (R/R) AML treated with a starting effective dose of venetoclax of 300 mg (at dose level 1) on days 2 to 21. After day 14, interruption of venetoclax was allowed if the day 14 bone marrow was hypocellular and without evidence of leukemia. Venetoclax dose adjustments were made for concomitant moderate and strong CYP3A inhibitors. Dose level 2 was explored (venetoclax 300 mg on days 2-8) and expanded after 3 of 6 patients experienced dose-limiting toxicity (DLT; cytopenias >43 days). After safety was established, 2 expansion cohorts were opened to confirm safety and efficacy. Cohort A included patients with R/R AML and cohort B included patients with newly diagnosed AML. Patients with adequate organ function (Eastern Cooperative Oncology Group performance status <2) were allowed on study as well as patients with prior venetoclax exposure.

At the time of data cutoff, 18 patients had been treated on study, which included 12 (67%) in the lead-in cohort, 5 (28%) in cohort A, and 1 (6%) in cohort B. The median age was 51 years (range, 29-71 years). Seventeen (94%) of the 18 patients had R/R AML with a median of 2 (range, 1-8) prior therapies. One (6%) patient had newly diagnosed treated-secondary AML. A total of 9 (50%) patients had adverse karyotype; 6 (33%) had complex karyotype and 6 (33%) had TP53 mutations. Seven (41%) patients with R/R AML had received prior venetoclax. A single patient with newly diagnosed AML (who had prior HMA plus venetoclax and allogeneic stem-cell transplant [allo-SCT] for myelodysplastic syndrome) achieved minimal residual disease–negative complete response (CR).

Of 16 evaluable patients with R/R AML, there was 1 (6%) CR, 6 (33%) CR with incomplete hematologic recovery, and 1 (6%) morphologic leukemia-free state resulting in an ORR of 44%. In patients without prior venetoclax exposure, the ORR was 60% (6/10) compared with just 17% (1/6 evaluable) among those with prior venetoclax exposure. Of the responding patients, 86% (6/7) went on to allo-SCT. The median OS overall was 6.4 months, and the landmark 6-month OS rate was 53%. Among responders, the median OS and relapse-free survival were not reached, with 6-month OS and relapse-free survival rates of 86%. The 4-week mortality rate was 11%, and the 8-week mortality rate was 22%. The starting dose level 1 was above the maximum tolerated dose of the combination (DLTs included prolonged neutropenia and thrombocytopenia). The most frequent grade 3/4 serious adverse events were infection, nausea, pneumonia, and myelosuppression.

In conclusion, CPX-351 plus 7 days of venetoclax was tolerable, with acceptable toxicities, among patients with R/R AML. In this high-risk cohort, CPX plus venetoclax demonstrated encouraging activity, particularly for patients without prior venetoclax exposure. Nearly all responders moved on to allo-SCT. Study enrollment continues.

Reference

Kadia TM, Borthakur G, Takahashi K, et al. Phase II Study of CPX-351 plus Venetoclax in Patients with Acute Myeloid Leukemia (AML). Presented at: 62nd American Society of Hematology Annual Meeting & Exposition; December 5-8, 2020. Abstract 28.

 

Related Items
Tibsovo Received a New Indication, in Combination with Azacitidine, for Newly Diagnosed Patients with AML and IDH1 Mutation
JHOP - June 2022 Vol 12, No 3 published on June 16, 2022 in FDA Oncology Update, Leukemia
Vidaza Received New Indication for Patients with Newly Diagnosed Juvenile Myelomonocytic Leukemia
JHOP - June 2022 Vol 12, No 3 published on June 16, 2022 in FDA Oncology Update, Leukemia, Pediatric Cancer
Arsenic Trioxide–Induced QTc Interval Prolongation and the Potential Benefit of Beta-Blockers in Patients with Acute Promyelocytic Leukemia: Case Series
JHOP - April 2022 Vol 12, No 2 published on May 3, 2022 in Case Reports, Leukemia, Adverse Events
Effect of Concomitant Azole Antifungals on Duration of Myelosuppression in Newly Diagnosed Patients with AML Receiving Venetoclax in Combination with Cladribine and Low-Dose Cytarabine
JHOP - March 2022 Vol 12 Special Feature published on March 22, 2022 in HOPA Abstracts, Leukemia
Dasatinib-Induced Gynecomastia in 2 Patients with Chronic Myeloid Leukemia: Case Reports and Review of the Literature
Jessie Signorelli, PharmD, BCOP, Amir T. Fathi, MD, Gabriela Hobbs, MD
JHOP - February 2022 Vol 12, No 1 published on March 1, 2022 in Case Reports, Leukemia, Adverse Events
Lidocaine plus Tetracaine–Medicated Patch Used for Propofol Sedation During Lumbar Punctures in Pediatric Patients with Blood Cancer
Lisa R. Garavaglia, PharmD , Frank Casey, MD, Lesley Cottrell, PhD, Claudiu Faraon-Pogaceanu, MD, Stephan Paul, MD, Melvin Lee Wright, DO
JHOP - February 2022 Vol 12, No 1 published on March 1, 2022 in Original Article, Pediatric Cancer, Leukemia, Lymphoma
Myeloablative and Reduced-Intensity Preparative Regimens for Allogeneic Transplant in the Outpatient versus Inpatient Setting in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndromes
Gretchen Pardo, PharmD, Beth Eddy, PharmD, BCOP, Zahra Mahmoudjafari, PharmD, BCOP, Dennis Grauer, PhD, MS, Joseph McGuirk, DO
JHOP - August 2021 Vol 11, No 4 published on August 17, 2021 in Original Article, Transplant, Leukemia, Myelodysplastic Syndromes, Conditioning Regimen
Pharmacy Resident–Led Medication Reconciliation and Patient Education Service in Adults with Leukemia Receiving Anticancer Oral Agents: A Pilot Study
Lily Y. Jia, PharmD, BCOP, Jessie Signorelli, PharmD, BCOP, Samantha O. Luk, PharmD, BCOP, E. Bridget Kim, PharmD, BCPS, BCOP, Gayle C. Blouin, PharmD, BCOP
JHOP - June 2021 Vol 11, No 3 published on June 16, 2021 in Original Article, Leukemia, Oncology Pharmacy Programs
Pegaspargase-Induced Diabetic Ketoacidosis in a Patient with Acute Lymphoblastic Leukemia
Ellen Madarang, PharmD, BCOP, Leslie Gallardo, PharmD, BCPS, Terrence Bradley, MD
JHOP - June 2021 Vol 11, No 3 published on June 16, 2021 in Case Reports, Acute Lymphoblastic Leukemia, Leukemia, Adverse Events
Oral Azacitidine Prolongs Survival in Patients with Acute Myeloid Leukemia
Robert J. Ignoffo, PharmD, FASHP, FCSHP, FHOPA
JHOP - April 2021 Vol 11, No 2 published on April 27, 2021 in From the Literature, Leukemia
Copyright © The Lynx Group, LLC. All rights reserved.