Multi-centric Study (CHEPRALL)

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.

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.

Study Overview

• Status: Completed
• Conditions: B ALL; CD22+ Expression; Refractory B-ALL
• Intervention / Treatment: Drug: Epratuzumab; Drug: Epratuzumab

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Angers, France, 49933
    • Angers University Hospital
  • Caen, France, 14000
    • University Hospital
  • Creteil, France, 94010
    • Henri Mondor Hospital
  • Lyon, France, 69437
    • Edouard Herriot Hospital
  • Marseille, France, 13373
    • Institut Paoli Calmette
  • Nantes, France, 44000
    • Nantes University Hospital
  • Paris, France, 75010
    • Saint Louis Hospital
  • Paris, France, 75015
    • St Antoine
  • Pessac, France, 33604
    • Haut-levêque Hospital
  • Poitiers, France, 86021
    • CHU de Poitiers
  • Toulouse, France, 37509
    • Purpan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
complete response rate (CR and CRp)

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Nantes University Hospital

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: October 12, 2010
• First Submitted That Met QC Criteria: October 12, 2010
• First Posted (Estimate): October 13, 2010

Study Record Updates

• Last Update Posted (Actual): February 27, 2018
• Last Update Submitted That Met QC Criteria: February 26, 2018
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: efficacy of Chemo-immunotherapy
• Additional Relevant MeSH Terms: Antineoplastic Agents; Antineoplastic Agents, Immunological; Epratuzumab
• Other Study ID Numbers: BRD/10/05-O