Clinical Trials /

BLINAtumomab After R-CHOP Debulking Therapy for Patients With Richter Transformation

NCT03931642

Description:

Blinatumomab (BLINCYTO) is a bi-specific T-cell engaging (BiTE®) antibody construct that transiently links CD3-positive T cells to CD19-positive B-cells, inducing T-cell activation and subsequent lysis of tumor cells. The investigators propose to evaluate the efficacy, safety and tolerability of blinatumomab administered after R-CHOP debulking therapy in patients with Richter Syndrome (RS) of diffuse large B-cell lymphoma (DLBCL) histology. The investigators hypothesize that 8-week blinatumomab induction therapy leads to Complete Response (CR) rate improvement (revised Cheson criteria) from a baseline of 7percent as observed in the prospective study evaluating R-CHOP.

Related Conditions:
  • Richter Syndrome
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: BLINAtumomab After R-CHOP Debulking Therapy for Patients With Richter Transformation
  • Official Title: BLINAtumomab After R-CHOP Debulking Therapy for Patients With Richter Transformation

Clinical Trial IDs

  • ORG STUDY ID: FILOCLL13-BLINART
  • NCT ID: NCT03931642

Conditions

  • Richter Syndrome

Interventions

DrugSynonymsArms
RCHOPR-CHOP- blinatumomab
BlinatumomabR-CHOP- blinatumomab

Purpose

Blinatumomab (BLINCYTO) is a bi-specific T-cell engaging (BiTE®) antibody construct that transiently links CD3-positive T cells to CD19-positive B-cells, inducing T-cell activation and subsequent lysis of tumor cells. The investigators propose to evaluate the efficacy, safety and tolerability of blinatumomab administered after R-CHOP debulking therapy in patients with Richter Syndrome (RS) of diffuse large B-cell lymphoma (DLBCL) histology. The investigators hypothesize that 8-week blinatumomab induction therapy leads to Complete Response (CR) rate improvement (revised Cheson criteria) from a baseline of 7percent as observed in the prospective study evaluating R-CHOP.

Trial Arms

NameTypeDescriptionInterventions
R-CHOP- blinatumomabExperimentalPatients will first undergo a prior debulking therapy including 2 cycles of R-CHOP. At Day1 (D1) : Rituximab 375 mg/m² Intravenous (IV) + Cyclophosphamide 750 mg/m² IV + Doxorubicin 50 mg/m² IV + Vincristine 1.4 mg/m² IV. From D1 to D5 : Prednisone 60 mg/m² Per Os (PO). Patients with CR and no measurable lesion left will not be treated further in the setting of the present trial. All the remaining patients will be continuing and treating on study with a single cycle of blinatumomab induction therapy : Blinatumomab at 9 μg/d IV by continuous vein infusion from day 1-7, 28 μg/d from day 8-14 and 112 μg/d from day 15-56. Patients who achieve an objective response after induction are eligible to receive one further optional cycle of blinatumomab consolidation : blinatumomab 9 μg/d IV by continuous vein infusion from day 1-7, 28 μg/d from day 8-14 and 112 μg/day IV from day 15-28.
  • RCHOP
  • Blinatumomab

Eligibility Criteria

        Inclusion Criteria:

          -  Confirmed diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic
             lymphoma according to the revised iwCLL criteria19 with biopsy proven transformation
             to diffuse large B-cell lymphoma, consistent with RS according to the 2016 WHO
             classification

          -  Both patients with previously treated or treatment-naïve CLL are eligible

          -  Age greater than or equal to 18 years

          -  Eastern Cooperative Oncology Group (ECOG) performance status <3

          -  Patients must meet the following hematologic criteria at screening, unless they have
             significant bone marrow involvement of either CLL or RS cells confirmed on biopsy:
             absolute neutrophil count ≥1.0 G/L, platelet count ≥50 G/L independent of transfusion
             within 7 days of screening

          -  Subject must have adequate coagulation, renal, and hepatic function at screening

          -  Adequate left ventricular ejection function (> 50 %)

          -  Patients who have undergone prior allogeneic hematopoietic stem-cell transplantation
             (HSCT) are eligible as long as they do not have significant active graft versus host
             disease and that their transplant day 0 is > 6 months from their first dose of
             protocol therapy

          -  Female patients of child bearing potential must have negative pregnancy test and use
             an effective method of birth control during treatment period and 48h thereafter; Males
             must use an effective method of birth control during treatment period and 48h
             thereafter.

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Patients with the Hodgkin variant of RS

          -  Patients with previously treated RS

          -  History or presence of clinically relevant disorder affecting the central nervous
             system (CNS)

          -  Known active DLBCL in the CNS (confirmed by cerebrospinal fluid analysis)

          -  Steroids treatment (≥ 20 mg for one week) before inclusion

          -  HSCT within 6 months before inclusion

          -  Active graft-versus-host disease

          -  History of other malignancies, except: i) malignancy treated with curative intent and
             with no recurrence over the last 5 years ii) adequately treated non-melanoma skin
             cancer without evidence of disease iii) adequately treated carcinoma in situ without
             evidence of disease

          -  History of human immunodeficiency virus

          -  Hepatitis B or C seropositivity (unless clearly due to vaccination)

          -  Pregnant or breastfeeding women

          -  Unwilling or unable to participate in all required study evaluations and procedures.

          -  Unable to understand the purpose and risks of the study and to provide a signed and
             dated informed consent form and authorization to use protected health information (in
             accordance with national and local subject privacy regulations)

          -  Abnormal screening laboratory values as defined as following: a) serum glutamate
             oxaloacetate transaminase and/or serum glutamate pyruvate transaminase and/or alkaline
             phosphatase > or =5 x upper limit of normal (ULN); b) Total bilirubin > or = 1.5 x
             ULN, unless due to Gilbert's disease; c) Creatinine > or = 2.0 x ULN or creatinine
             clearance <50 mL/min (calculated).

          -  Fertile male and female patients who cannot or do not wish to use an effective method
             of contraception during treatment and for 48h after the final treatment used for the
             purposes of the study

          -  Treatment with other investigational agent or participating to another trial within 30
             days prior to entering the study

          -  No affiliated to social security
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete remission (CR) rate according to the revised Lugano criteria
Time Frame:at week 16 from baseline
Safety Issue:
Description:the objective response rate to one 8-week cycle of blinatumomab following a debulking therapy with 2 R-CHOP cycles

Secondary Outcome Measures

Measure:Number of patients with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame:From the first treatment administration and during treatment period (R-CHOP and blinatomomab)
Safety Issue:
Description:safety and toxicity of blinatumomab after 2 cycles of R-CHOP
Measure:overall response
Time Frame:At week 16 from baseline, after blinatumomab induction and at week 24 after blinatumomab consolidation.
Safety Issue:
Description:Overall response rate (revised Lugano criteria) after the first and second cycle of blinatumomab,
Measure:CR rate
Time Frame:After blinatumomab consolidation (total of 4 weeks) at week 24 from the beginning of study treatment.
Safety Issue:
Description:CR rate (revised Lugano criteria) after the second cycle of blinatumomab

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:French Innovative Leukemia Organisation

Last Updated

July 17, 2019