Results of Cancer and Leukemia Group B 10102 (Alliance), a Phase 1/2 Study.

BACKGROUND

Acute lymphoblastic leukemia (ALL) in adults is aggressive, with long-term outcomes impacted by treatment resistance and toxicity. CD52 is expressed in most cases of B- and T-lineage ALL. Alemtuzumab, a humanized immunoglobulin G1 monoclonal antibody that targets CD52, was identified as a potential agent to improve treatment efficacy without increasing toxicity.

METHODS

In this phase 1/2 study (Cancer and Leukemia Group B [CALGB] 10102, NCT00061945), a course of single-agent alemtuzumab was intercalated into CALGB 19802 backbone chemotherapy after the third course of intensive chemotherapy in those who were CD52+ at diagnosis. Phase 1 tested three dose levels of subcutaneous alemtuzumab (10, 20, and 30 mg 3 times weekly for 4 weeks/12 doses) and demonstrated that 30 mg was tolerable. Phase 2 established feasibility.

RESULTS

The study enrolled 295 evaluable patients (115 in phase 1, 180 in phase 2); 206 (69.8%) were CD52+. Among evaluable CD52+ patients, 43.7% (90/206) completed the first three treatment modules; 97.8% (88 of 90) were treated with alemtuzumab. Alemtuzumab was associated with cytomegalovirus viremia, which occurred in 23.3% (14 of 60) of patients during and 29.2% (19 of 65) after alemtuzumab treatment. With a median follow-up of 101.2 months, median overall survival (OS) was 26.3 months (3-year rate, 44%; 5-year rate, 36%; 10-year rate, 31%). Landmark analysis at the start of the fourth course of treatment demonstrated no difference in OS or disease-free survival between patients who did and who did not receive alemtuzumab.

CONCLUSION

Alemtuzumab was feasible to administer in adults with ALL receiving intensive chemotherapy, but was without evidence of benefit.