Clinical trial NCT01219816: Multi-centric Study
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: B ALL
CD22+ Expression
Refractory B-ALL
Keywords: efficacy of Chemo-immunotherapy
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2010-10-13
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: complete response rate (CR and CRp)
Secondary outcomes:
measure: Overall response rate (ORR)(CR, CRp and PR)
measure: Overall survival
measure: Disease free survival
measure: CD22 expression after Epratuzumab
measure: Safety and tolerance of Epratuzumab in combination with chemotherapy
Other outcomes:
Locations:
city: Angers
country: France
facility: Angers University Hospital
city: Caen
country: France
facility: University Hospital
city: Creteil
country: France
facility: HEnri Mondor Hospital
city: Lyon
country: France
facility: Edouard Herriot Hospital
city: Marseille
country: France
facility: Institut Paoli Calmette
city: Nantes
country: France
facility: Nantes University Hospital
city: Paris
country: France
facility: Saint Louis Hospital
city: Paris
country: France
facility: St Antoine
city: Pessac
country: France
facility: Haut-Leveque Hospital
city: Poitiers
country: France
facility: CHU de Poitiers
city: Toulouse
country: France
facility: Purpan Hospital
Study officials:
affiliation: Nantes University Hospital
name: Patrice CHEVALLIER, MD
role: PRINCIPAL_INVESTIGATOR
References: