In this phase 3, non-inferiority study patients were randomized to receive 3 cycles of HD Ara-C using either 18 g/m2 (arm A) or 12 g/m2 (arm B), 3 cycles each for consolidation.
Between August 2012 and May 2015, 170 patients of AML, in morphological CR following induction (3 + 7) have been recruited. Relapse-free survival (RFS) was the primary end point. Overall survival (OS), hematological/non-hematological toxicity, antimicrobial/GCSF requirement, transfusions and hospital stay were secondary end points. For a pre-planned interim analysis, 90 patients randomized till February 28, 2014, have been analyzed; with 45 patients in each arm. Median age was 12.5 years (range, 1 to 64). Cytogenetically, 35 (39%) of patients were in favorable risk, intermediate -38 (42%) and poor risk-9(10%) category. Patients' characteristics were similar in both arms. Analysis has been done intention to treat. Data has been censored till July 31, 2014.
79/90 patients completed the treatment protocol; Arm A = 40, Arm B = 39, p = 0.74. Median duration of consolidation was 77.5 days, (range 58-148 days) and was similar in the two study arms (p = 0.16). There was no difference as regards the infectious/non-infectious toxicity, neutropenic fever (p = 0.45), antibiotic use (first/second/third line, p = 0.50), therapeutic anti-fungal use or blood/platelet transfusions (p = 0.43/0.75). Total hospitalization was not significantly different, but the high dose arm (arm A) required significantly more short admissions (daycare facility, <24 hours) for supportive care (12.2 days vs 10.34 days, p = 0.043) and received G-CSF for a longer period; 8.58 days vs 6.4 days, p = 0.042. 48 patients relapsed at a median of 12 months, relapse rate was similar in both arms; 25 (55%) in high dose arm vs. 23(51%) in lower dose arm, p= 0.67. Kaplan-Meier curves truncated at 12 months of follow-up showed an estimated OS of 89% (95% CI 0.73-0.95) in the 18 g/m2 (arm A) vs. 61% (95% CI 0.42-0.75) in the 12 g/m2 (arm B), p < 0.0023. Similarly, RFS was 58.6%( 95% CI 0.41-0.72) in arm A and 41.9%( 95% CI 0.25-0.57) in arm B,p < 0.036.
At interim analysis, consolidation therapy using 18 g/m2 Ara-C appears to confer better relapse-free and overall survival.
Clinical trial identification
All authors have declared no conflicts of interest.