Phase 1/2 Trial of CLAG-M with Dose-Escalated Mitoxantrone in Combination with Fractionated-Dose Gemtuzumab Ozogamicin for Newly Diagnosed Acute Myeloid Leukemia and Other High-Grade Myeloid Neoplasms.
Colin D GodwinEduardo Rodríguez-ArbolíMegan OthusAnna B HalpernJacob S AppelbaumMary-Elizabeth M PercivalPaul C HendrieVivian G OehlerSiobán B KeelJanis L AbkowitzJason P CooperRyan D CassadayElihu H EsteyRoland Bruno WalterPublished in: Cancers (2022)
Gemtuzumab ozogamicin (GO) improves outcomes when added to intensive AML chemotherapy. A meta-analysis suggested the greatest benefit when combining fractionated doses of GO (GO3) with 7 + 3. To test whether GO3 can be safely used with high intensity chemotherapy, we conducted a phase 1/2 study of cladribine, high-dose cytarabine, G-CSF, and dose-escalated mitoxantrone (CLAG-M) in adults with newly diagnosed AML or other high-grade myeloid neoplasm (NCT03531918). Sixty-six patients with a median age of 65 (range: 19-80) years were enrolled. Cohorts of six and twelve patients were treated in phase 1 with one dose of GO or three doses of GO (GO3) at 3 mg/m 2 per dose. Since a maximum-tolerated dose was not reached, the recommended phase 2 dose (RP2D) was declared to be GO3. At RP2D, 52/60 (87%) patients achieved a complete remission (CR)/CR with incomplete hematologic recovery (CRi), 45/52 (87%) without flow cytometric measurable residual disease (MRD). Eight-week mortality was 0%. Six- and twelve-month event-free survival (EFS) were 73% and 58%; among favorable-risk patients, these estimates were 100% and 95%. Compared to 186 medically matched adults treated with CLAG-M alone, CLAG-M/GO3 was associated with better survival in patients with favorable-risk disease (EFS: p = 0.007; OS: p = 0.030). These data indicate that CLAG-M/GO3 is safe and leads to superior outcomes than CLAG-M alone in favorable-risk AML/high-grade myeloid neoplasm.
Keyphrases
- newly diagnosed
- acute myeloid leukemia
- high grade
- end stage renal disease
- high dose
- chronic kidney disease
- low grade
- high intensity
- ejection fraction
- free survival
- prognostic factors
- acute lymphoblastic leukemia
- allogeneic hematopoietic stem cell transplantation
- peritoneal dialysis
- bone marrow
- low dose
- randomized controlled trial
- adipose tissue
- rheumatoid arthritis
- insulin resistance
- locally advanced
- cardiovascular events
- skeletal muscle
- systemic lupus erythematosus
- patient reported
- rectal cancer
- deep learning