Testing a Reduced Conditioning Regimen FB2A2 Preceded by a Fractionated Radio-immunotherapy (RIT) With 90Y-Epratuzumab Before Allogeneic Stem Cell Transplantation for Patients With Lymphocyte B CD22 Positive Acute Lymphoblastic Leukemia

Lymphocyte B CD22 Positive Acute Lymphoblastic Leukemia Clinical Trial

— EPRALLO  

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02577094
• Other study ID #: RC14_0429
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• First received: October 2, 2015
• Last updated: January 17, 2017
• Est. completion date: January 2017

Study information

• Verified date: January 2017
• Source: Nantes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Determination of the maximum tolerated dose (MTD) of fractionated RIT with epratuzumab radiolabeled with yttrium-90 (90Y-epratuzumab) preceding a reduced conditioning regimen FB2A2 before allogeneic stem cell transplantation.

Description:

• Physical examination (screening and follow-up)

• Complete blood counts (screening and follow-up)

• Dosage of FLT3-ligand in plasma (screening and follow-up)

• Blood ionogramme, creatinine hepatic work-up (screening and follow-up)

• Left ventricular ejection fraction at pre-implant assessment

• Immunization test (screening and follow-up)

• Bone marrow aspiration or/and blood CD 22 immunophenotype for minimal residual disease evaluation (screening and follow-up)

• All exams which were initially abnormal and which are necessary for response evaluation and All exams which are needed in case of relapse suspicion.

• Pharmacokinetic of 90Y-hLL2

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18

• Acute lymphoblastic Leukemia (ALL) CD22 + B-type in RC1 with high risk

• B-Cell Acute Lymphoblastic Leukemia (ALL) CD22+ beyond RC1.

• Expression of CD22 = 30% in tumor population evaluated by flow cytometry or immunohistochemistry at diagnosis stage or relapse stage.

• HLA-identical donor intra family or not, without major HLA mismatch (9 / 10th accepted) without contra-indication for stem cell mobilization

• ECOG (Eastern Cooperative Oncology Group) = 2

• Having or not received previously Epratuzumab

• Eligible for an allograft with reduced conditioning regimen

• With a signed informed consent

• Patient in age of children bearing with adequate contraception

• Patient affiliated to or beneficiary of the National Health Service

Exclusion Criteria:

• T-cell ALL

• Known hypersensibility to 90Y-DOTA-hLL2

• Immunization against hLL2 for patients having already received one or several injections of this antibody

• Patient eligible for myeloablative conditioning regimen

• Other prior malignancies must have had at least a 2-year disease-free interval with the exception of successfully treated carcinoma skin cancer or carcinoma in situ of the cervix.

• Patient with progressive psychiatric condition.

• HIV positive, hepatitis B-antigen positive, or hepatitis C positive patients who need a treatment

• Pregnant or breast-feeding women

• Women with childbearing potential without effective contraception

• Serious concomitant and uncontrolled infection

• Usual contraindications in the allogeneic transplant:

• Adult patient protected by the French law

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Lymphocyte B CD22 Positive Acute Lymphoblastic Leukemia
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• 90Y-DOTA-Epratuzumab IgG/Epratuzumab IgG
2 injections of 90Y-DOTA- hLL2 IgG- hLL2 IgG at day -21 and day -14. (The 2 drugs are mixted in the same infusion)
• Busulfan
Between the last injection of 90Y-DOTA- hLL2 IgG/hLL2 IgG (J-14) and the allogeneic stem cell transplantation

Biological:
• allogeneic stem cell transplantation.
At Day 0

Drug:
• Fludarabine
Between the last injection of 90Y-DOTA- hLL2 IgG/hLL2 IgG (J-14) and the allogeneic stem cell transplantation

Biological:
• Thymoglobulines
Between the last injection of 90Y-DOTA- hLL2 IgG/hLL2 IgG (J-14) and the allogeneic stem cell transplantation

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Nantes University Hospital	Immunomedics, Inc., Institut Cancerologie de l'Ouest

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of the maximum tolerated dose (MTD)	Patient toxicity will be evaluated according to NTCAE V4 criteria.	6 weeks
Secondary	Overall survival		Month 12
Secondary	Disease free survival at one year post-transplant		Month 12
Secondary	Incidence of relapse at 1 year post-transplant		Month 12
Secondary	Non relapse mortality at day 100 post-transplant		Day 100
Secondary	Non relapse mortality at one year post-transplant		Month 12
Secondary	Hematologic reconstitutions post-transplant	Biological follow-up	Month 3
Secondary	Immune reconstitutions post-transplant	Biological follow-up	Month 3
Secondary	Incidence of acute and chronic GVHD		Month 3 and 12
Secondary	Chimerism post-transplant	Blood sample and/or bone marrow analysis by molecular biology	Month 3
Secondary	Residual disease post-transplant	by flow cytometry analysis	Month 3 and Month 12
Secondary	Toxicity of RIT	biological follow up and physical examination	Week 6 and Month 12
Secondary	Tolerance of RIT	biological follow up and physical examination	Week 6 and Month 12
Secondary	Immunization analysis : detection of antibody anti epratuzumab	By ELISA assay	Month 12
Secondary	90Y-DOTA-Epratuzumab blood pharmacokinetics	Detection of the radioactivity within the patient's blood samples	Month 2
Secondary	Dosage of FLT3-ligand in plasma and correlation with efficacy and toxicity of RIT	by biological assay	Month 12