CD22+ Relapsed/Refractory B-ALL Clinical Trial
Official title:
Randomized Phase II Study Evaluating the Efficacy of 90Yttrium-epratuzumab Tetraxetan Radioimmunotherapy in Adults With CD22+ Relapsed/Refractory B-ALL
The investigators propose a randomized phase 2 study evaluating 90Y-epratuzumab tetraxetan for relapsed/refractory CD22+ B-ALL adult patients using the recommended activity of 370 MBq/m² x 2. in order to confirm the investigators' previous results. The cut-off of 70% for the expression of CD22 has been chosen in order to propose this protocol to all adults with CD22+ B ALL in relapse or with refractory disease. Indeed, median expression of CD22 is almost 100% in this setting but some patients are documented between 70 and 100%. RIT will be assessed in comparison with standard of care salvage chemotherapy regimens. Only three standard salvage chemotherapy regimens will be permitted in order to avoid too much bias for the comparative analysis of clinical efficacy.
The experimental treatment will consist on 2 injections of 370 MBq/m2 of 90Y-epratuzumab
tetraxetan fractionated RIT at day 1 and day 8. The first infusion of 90Y-epratuzumab
tetraxetan will be co-injected for the six first patients in Nantes with 111In-epratuzumab
tetraxetan for dosimetry purpose.
Subjects randomized to receive standard of care salvage chemotherapy/ immunotherapy regimen
will be assigned per investigator's choice to one of the following chemotherapy/
immunotherapy regimens:
1. FLAG +- anthracycline based regimen (such as Idarubicin 10 mg/m2 days 1, 3; fludarabine
30 mg/m2 days 1-5, cytarabine 2 g/m2 days 1-5).
For subject's >60 years : idarubicin 5 mg/m2 day 1,3, fludarabine 20 mg/m2 days 1-5,
cytarabine 1 g/m2 days 1-5.
2. Clofarabine or clofarabine based regimens. Clofarabine use as a single agent should
follow the recommended prescribing information. Clofarabine combination based regimens
should use >=20mg/m2/day for up to 5 days.
3. Hyper-C-VAd regimen: hyperfractionated cyclophosphamide 300 mg/m2 intravenously(i.v.)
every 12 hours for 6 doses Days 1 to 3 + vincristine 2 mg i.v.Days 4 and 11;
doxorubicin 50 mg/m2 i.v. over 24 hours via central venous catheter Day 4; and
dexa-methasone 40 mg daily Days 1 to 4 and 11 to 14.
4. Blinatumomab (Blincyto®) is administered as a 28-day continuous infusion (9µg/d for
days 1-7; 28µg/d thereafter, followed by 2 weeks of rest for up to 2 cycles. Patients
should be hospitalized the first 9 days during the first cycle and at least the first 2
days during the second cycle.
A second RIT cycle (consolidation) will be allowed in the experimental group in case of
response (CR or CRp).
From an ethical point of view, it will be also permitted to propose the RIT experimental
treatment in the control group in case of treatment failure or relapse during the 6 months
following inclusion. Follow-up will be also 12 months from the RIT for these patients.
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