2019 ASCO Annual Meeting!
Session: Pediatric Oncology I
Type: Oral Abstract Session
Time: Friday May 31, 2:45 PM to 5:45 PM
AAML 1421, a phase I/II study of CPX-351 followed by fludarabine, cytarabine, and G-CSF (FLAG) for children with relapsed acute myeloid leukemia (AML): A Report from the Children’s Oncology Group.
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr 10003)
Author(s): Todd Michael Cooper, Michael Absalon, Todd Allen Alonzo, Robert B Gerbing, Kasey Joanne Leger, Betsy A Hirsch, Jessica Anne Pollard, Bassem I. Razzouk, Richard Aplenc, E. Anders Kolb; Seattle Children's Cancer and Blood Disorders Center, University of Washington, Seattle, WA; Cincinnati Children's Hospital Medical Center, Cincinnati, OH; University of Southern California Children's Oncology Group, Arcadia, CA; Children's Oncology Group, Arcadia, CA; Seattle Children's Hospital, Cancer and Blood Disorders Center, Seattle, WA; University of Minnesota, Minneapolis, MN; Dana-Farber Cancer Institute/Boston Children's Hospital, Boston, MA; Peyton Manning Childrens Hosp St Vincent, Indianapolis, IN; Children's Hospital of Philadelphia, Philadelphia, PA; The Childrens Hosp At Montefiore, Bronxville, NY
Background: Effective regimens with favorable toxicity profiles are needed for heavily pre-treated children with relapsed AML. AAML1421 is a Phase I/II study of CPX-351, a liposomal preparation of cytarabine and daunorubicin demonstrating efficacy in adults. AAML1421 sought to determine the recommended Phase 2 Dose (RPD2) of CPX-351 and the response rate (complete response (CR) + complete response without platelet recovery (CRp)) after up to 2 cycles of therapy. Methods: Children > 1 and ≤ 21 years of age with relapsed/refractory AML were eligible for dose finding, and those in first relapse were eligible for efficacy. A modified rolling six design was used for dose-limiting toxicity (DLT) assessment which occurred in Cycle 1. Dose level 1 (DL1) was 135 units/m2 on days 1, 3, and 5 with a single dose de-escalation to 100 units/m2 if DL1 was intolerable. The Efficacy Phase used a Simon-two stage design. The response rate was determined after up to 2 cycles of therapy (Cycle 1: CPX-351; Cycle 2: FLAG). The Overall Response Rate (ORR) was defined as CR+CRp+CRi (CRi = CR with incomplete hematologic recovery). Results: Thirty-eight patients (pts) enrolled: 6 in dose-finding and 32 in the efficacy phase. DLT occurred in 1/6 patients and was a grade 3 decrease in ejection fraction(EF). This was the only Grade 3 cardiac toxicity. Therefore, 135 units/m2 on days 1, 3, 5 was the RP2D. All dose finding pts were eligible for efficacy determination. One pt in the efficacy phase was unevaluable. The most common ≥ Grade 3 toxicities in Cycle 1 included fever/neutropenia (45%), infection (47%), and rash (40%). There was no toxic mortality. Best responses included 20 CR (54%), 5 CRp (14%), and 5 CRi (14%). Seventy percent achieved best response after cycle 1. Twenty-one of 25 patients with CR/CRp had no detectable residual disease (RD) (84%) by flow cytometry. HSCT was used as consolidation in 23/29 responders (79%); 18 of 23 (78%) had no detectable RD prior to HSCT. Conclusions: The RP2D of CPX-351 is 135 units/m2/dose on days 1, 3, 5. CPX-351 was well tolerated and protocol therapy was effective with CR+CRp rates of 68.3% (90% CI 52.9% to 78.0%) and ORR (CR+CRp+CRi) of 81.1% (90% CI 67.4% to 88.8%). AAML1421 response rates are superior to any published North American cooperative group clinical trial for children with AML in first relapse. Clinical trial information: NCT02642965
1. Effect of intensification of induction II chemotherapy and liberalization of stem cell donor source on outcome for children with high risk acute myeloid leukemia: A report from the Children’s Oncology Group.