Table 2.

Phase 3 Clinical Trials for relapsed acute lymphoblastic leukemia (ALL)

Group	Years	Age (years)	Type of relapse	No. of patients	EFS/PFS	OS	Comments
ALL R3	2003–2009	1–18	First relapse	239 (216 randomized)	3-y Mitoxantrone arm: 64.6%; Idarubicin arm: 35.9%	3-y Mitoxantrone arm: 69%; Idarubicin arm: 45.2%	Mitoxantrone arm more effective than idarubicin arm
ALL-REZ-BFM 2002	2003–2012	1–18	First relapse	538 (420 randomized)	5-y Prot II-IDA arm: 60%; R arm: 53%	5-y Prot II-IDA arm: 69%; R arm: 63%	Post-induction therapy with Protocol II-IDA was associated with fewer subsequent relapses compared to R-courses
DCOG Rel-ALL 98	1999–2006	1–18	Early and late	158 (99 reported)	5-y Early: 12%; Late: 35%		Early relapses have poorer outcome
NOPHO (multiple protocols)	1992–2011	1–14.9	First relapse	516	5-y: 44%	5-y 51.5%	Improved outcomes over time mainly due to more late relapses over the years
COG AALL0433	2007–2013	1–30	Late medullary or very early iCNS relapsed B-ALL	275 (271 eligible)	3-y late medullary 77.5%; early iCNS 41.4%	3-y late medullary 81.5%; early iCNS 51.7%	HSCT did not improve OS in late medullary relapses. Early iCNS relapses do poorly
COG AALL1331	2014–2019	1–30	IR/HR	220 (208 randomized)	59.3% (blinatumomab arm)	79.4% (blinatumomab arm)	Blinatumomab superior to standard chemotherapy as post-reinduction consolidation in IR/HR relapses
NCT02435849	2015–2017	3–12	CD19+ relapsed or refractory B-cell ALL	75	1 y: 50%	1 y: 76%	Durable remission with single infusion of tisagenlecleucel (CTL019)

BFM Berlin-Frankfurt-Münster, COG Children’s Oncology Group, DCOG Dutch Childhood Oncology Group, EFS Event-free survival, HR High risk, HSCT Hematopoietic stem/progenitor cell transplantation, iCNS Isolated central nervous system, IDA Idarubicin, IR Intermediate risk, NOPHO Nordic Society for Pediatric Hematology and Oncology, OS Overall survival, PFS Progression-free survival, Prot Protocol