Multi-centric Study

Study Overview
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Brief Summary
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Patients with relapsed/refractory adult acute lymphoblastic leukemia (ALL)have a very dismal prognosis. In this case, allogeneic transplantation is the only curative treatment when patient have obtained a second complete remission (CR. In France, in patients younger than 60 years old,the HyperCVAD regimen used by the MDAnderson in Houston is generally applied. In older patients (>=60 years)or young patients <= 60 years no eligible for intense chemotherapy, a combination of vincristine + Dexamethasone is generally chosen in order to avoid too much toxicity but the result is worse in term of CR. More than 90% of ALL with a B phenotype (2/3 of cases in adults)express the surface antigen CD22 on leukemic blasts which thus represents an interesting target for therapy. Epratuzumab is a humanized anti-CD22 antibody produced by Immunomedics, Inc, Morris Plain (New Jersey, USA). Epratuzumab has already shown efficacy in lymphoma patients. Only one study, including 15 children, has been published so far reporting the efficacy and the toxicity of Epratuzumab in the setting of ALL in monotherapy, one can observe 8 stable disease, 3 progressions and 4 partial responses. When combining chemotherapy and Epratuzumab, 9CR were observed with acceptable toxicity. Tolerance was acceptable. The French GRAALL group proposes to test an age-adapted combination of chemotherapy + Epratuzumab, in refractory/relapses CD22+ B ALL patients in order to improve their prognosis, in term of CR, survival and of number of patients eligible for allograft.

Official Title
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Phase II, Multicenter, Open Label, Prospective to Evaluate Efficacy and Tolerance of a Chemoimmunotherapy With HyperCVAD or Vincristine/Dexamethasone Plus the Anti-CD22 Monovlonal Antobody Epratuzumab for the Treatment of Adult Relapsed/Refractory CD22+ B-Acute Lymphoblastic Leukaemia Patients : CHEPRALL Study, a GRAALL Study.

Conditions
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B ALL, CD22+ Expression, Refractory B-ALL

Intervention / Treatment
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* Drug: Epratuzumab
* Drug: Epratuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >= 18 years B-ALL (OMs) with >= 20 % of blasts in bone marrow CD22+ expression >= 30% of the blast population Refractory B-ALL defined by treatment failure after 2 successive courses of induction therapy or relapse < 6 months after first CR First relapse of B-ALL Second relapse or beyond Performance status 0-2 Creatinine clearance >= 50 ml/min (Cockroft formula) Serum bilirubine <= 30 µmom/l Written informed consent Exclusion Criteria: T-ALL Meningeal involvement CD22 expression on tumor cells or < 30% HIV positive Active Hepatitis B or C Left ventricular ejection fraction < 50% in patients <60 years Contra-indication to Epratuzumab Previous or concurrent second malignancy except for adequately treated basal cell carcinoma of the skin, curatively treated in situ carcinoma of the cervix, curatively treated solid cancer, with no evidence of disease for at least 5 years Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule Participation at the same time in another study in which investigational drugs are used Absence of written informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients under 60 years<br>Hyper CVAD regimen + Epratuzumab (Cyclophosphamide Vincristine Doxorubicin Dexamethasone) | Drug: Epratuzumab<br>* Combination of chemotherapy + Epratuzumab<br>|
| Experimental: Patients older than 60 years or < =60 years<br>Vincristine + Aracytine + Dexamethasone | Drug: Epratuzumab<br>* Vincristine + Dexamethasone + Epratuzumab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| complete response rate (CR and CRp) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR)(CR, CRp and PR) |  |  | 
| Overall survival |  |  | 
| Disease free survival |  |  | 
| CD22 expression after Epratuzumab |  |  | 
| Safety and tolerance of Epratuzumab in combination with chemotherapy |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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efficacy of Chemo-immunotherapy