Study Evaluating the Efficacy of 90Yttrium-epratuzumab in Adults With CD22+ Relapsed/Refractory B-ALL

NCT02844530 | Withdrawn Phase 2

• 1 other identifier: RC15_0088
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

CD22+ Relapsed/Refractory B-ALL

Keywords

adults

Outcome Measures

Primary Outcomes (1)

• Compare the complete response rate (CR + CRp) in the two arms

  Evaluated between 4 and 6 weeks from day 1. Blood and bone marrow analysis.

  Week 4 to Week 6

Secondary Outcomes (15)

• Overall survival: overall and comparison between both groups

  Month 1 to Month 12

• Disease free survival

  Month 1 to Month 12

• time to disease progression

  Month 1 to Month 12

• duration of response

  Month 1 to Month 12

• CD22 expression

  Month 1 to Month 12

Study Arms (2)

RIT

EXPERIMENTAL

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.

Drug: 90Y-epratuzumab tetraxetan

chemotherapy/ immunotherapy

ACTIVE COMPARATOR

chemotherapy/ immunotherapy regimen will be assigned per investigator's choice to one of the following chemotherapy/ immunotherapy regimens: 1. FLAG +- anthracycline based regimen 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®) : 28-day continuous infusion (9µg/d for days 1-7; 28µg/d thereafter, followed by 2 weeks of rest for up to 2 cycles.

Drug: chemotherapy/ immunotherapy

Interventions

90Y-epratuzumab tetraxetan DRUG

The Primary objective is to compare the complete response rate (CR + CRp) after 2 injections of 370 MBq/m² of 90Y-epratuzumab tetraxetan RIT at day 1 and day 8 versus standard of care salvage chemotherapy regimens in adult CD22+ relapsed/refractory B-ALL. 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

Also known as: 90Y-DOTA-hLL2 or 90Y-DOTA-Epratuzumab

RIT

chemotherapy/ immunotherapy DRUG

chemotherapy/ immunotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age\>= 18 years old
• Philadelphia positive or negative B-ALL (OMS) with \>5% of blasts in bone marrow with or without extramedullary disease
• CD22+ expression \>=30% of the blast population
• Refractory B-ALL defined by :
• treatment failure after 1 or 2 successive courses of induction therapy or first relapse \<6 months from CR.
• First relapse, second or third relapse.
• Unresponsive to prior treatment with \>=1 second/third (dasatinib, nilotinib, bosutinib, ponatinib) generation TKIs and standard induction chemotherapy for Ph+ B-ALL patients only.
• Peripheral absolute lymphoblast count \<10000/µL: hydroxyurea and/or steroids/vincristine treatment within 2 weeks of randomization is allowed to reduce circulating blasts.
• ECOG (Eastern Cooperative Oncology Group) \< 2
• Creatinine clearance \>= 50 ml/min (Cockroft formula) or serum creatinine \<=1.5 x ULN
• Adequate hepatic function: total serum bilirubin \< 1.5 x upper limit of normal (ULN) except for documented Gilbert syndrome or considered tumor related; \<=5 ULN for transaminases except if considered tumor related
• Written informed consent
• Having or not received previously Epratuzumab: in case of having received previously epratuzumab, patients should be free of HAHA (anti-epratuzumab antibodies).
• Patient affiliated to or beneficiary of the National Health Service
• Patients with lymphoblastic lymphoma can be included if they satisfied all eligibility criteria.

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (1)

CHU de Clermont-Ferrand

Clermont-Ferrand, 63000, France

Location

MeSH Terms

Interventions

Drug Therapy; Immunotherapy

Intervention Hierarchy (Ancestors)

Therapeutics; Immunomodulation; Biological Therapy

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2015
• First Posted: July 26, 2016
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: January 19, 2017

Record last verified: 2017-01

Locations

FR (1)