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

• Sponsor: French Innovative Leukemia Organisation (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03931642
• Collaborator: Amgen (Industry)
• Enrollment: 41
• Locations: 28
• Arm: 1
• Anticipated Duration (Months): 43
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Richter Syndrome	Drug: RCHOP; Drug: Blinatumomab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: BLINAtumomab After R-CHOP Debulking Therapy for Patients With Richter Transformation
• Actual Study Start Date: Jul 5, 2019
• Actual Primary Completion Date: Oct 1, 2021
• Anticipated Study Completion Date: Feb 4, 2023

Arms and Interventions

Arm

Intervention/Treatment

Experimental: R-CHOP- blinatumomab Patients 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.

Drug: RCHOP; D1 : Rituximab 375 mg/m² 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 PO.; Drug: Blinatumomab; Blinatumomab by continuous vein infusion

Outcome Measures

Primary Outcome Measures

1. Complete remission (CR) rate according to the revised Lugano criteria [at week 16 from baseline]

   the objective response rate to one 8-week cycle of blinatumomab following a debulking therapy with 2 R-CHOP cycles

Secondary Outcome Measures

1. Number of patients with treatment-related adverse events as assessed by CTCAE v4.0 [From the first treatment administration and during treatment period (R-CHOP and blinatomomab)]

   safety and toxicity of blinatumomab after 2 cycles of R-CHOP

2. overall response [At week 16 from baseline, after blinatumomab induction and at week 24 after blinatumomab consolidation.]

   Overall response rate (revised Lugano criteria) after the first and second cycle of blinatumomab,

3. CR rate [After blinatumomab consolidation (total of 4 weeks) at week 24 from the beginning of study treatment.]

   CR rate (revised Lugano criteria) after the second cycle of blinatumomab

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Chu Amiens	Amiens		France	80054
2	CHU ANGERS - Maladies du sang	Angers		France	49933
3	Ch Cote Basque	Bayonne		France	64109
4	Hopital Jean Minjoz	Besançon		France	25000
5	Hôpital Avicenne - Centre de Recherche Clinique	Bobigny		France	93009
6	CH de Béziers - Hématologie	Béziers		France	34500
7	CHU Caen - IHBN - Hématologie Clinique	Caen		France	14033
8	CHU Estaing - Hématologie Clinique Adulte	Clermont-Ferrand		France	63000
9	CHU Grenoble - Hématologie	Grenoble		France	388043
10	Centre Hospitalier du Mans	Le Mans		France	72000
11	Hôpital Saint Vicent de Paul	Lille		France	59000
12	Centre Léon Bérard - Hématologie	Lyon		France	69373
13	Institut Paoli-Calmettes - Hématologie Clinique	Marseille		France	13273
14	HOPITAL SAINT ELOI - Hematologie	Montpellier		France	34295
15	Hopital E.Muller	Mulhouse		France	68100
16	CHU DE NANTES - Hematologie clinique	Nantes		France	44093
17	Hopital Pitie Salpetriere Service Hematologie Clinique - Pavillon de L'Enfant Et Adolescent	Paris		France	75651
18	CENTRE HOSPITALIER SAINTJEAN - Hématologie Clinique	Perpignan		France	66000
19	Bordeaux Pessac	Pessac		France	33604
20	Centre Hospitalier Lyon Sud	Pierre-Bénite		France	69495
21	Hôpital de la Milétrie - Hématologie et Thérapie Cellulaire	Poitiers		France	86021
22	Hôpital Robert Debré - Hématologie Clinique	Reims		France	51092
23	CHU Pontchaillou - Hématologie Clinique BMT-HC	Rennes		France	35033
24	Centre Henri Becquerel - Service Hématologie Clinique	Rouen		France	76038
25	Hôpital Hautepierre - Hématologie	Strasbourg		France	67098
26	IUCT ONCOPOLE - Hématologie	Toulouse		France	31059
27	Hôpital Bretonneau - Hématologie et Thérapie Cellulaire	Tours		France	37044
28	Hôpitaux de Brabois - Hématologie Adulte	Vandœuvre-lès-Nancy		France	54511

Sponsors and Collaborators

• French Innovative Leukemia Organisation
• Amgen

Investigators

• Principal Investigator: Romain GUIEZE, University Hospital, Clermont-Ferrand

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: French Innovative Leukemia Organisation
• ClinicalTrials.gov Identifier: NCT03931642
• Other Study ID Numbers: FILOCLL13-BLINART
• First Posted: Apr 30, 2019
• Last Update Posted: Jul 27, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Blinatumomab

Study Results

No Results Posted as of Jul 27, 2022