Bendamustine and Rituximab (BR) as Induction and Maintenance in Relapsed and Refractory Chronic Lymphocytic Leukemia

• Conditions: Chronic Lymphocytic Leukemia
• Interventions: Drug: BR as Maintenance

• Registration Number: NCT03847727
• Lead Sponsor: Pirogov Russian National Research Medical University

Brief Summary

CLL is an incurable disease with conventional chemotherapy. In the absence of TP53 disruption, a chemoimmunotherapy (CIT) regimen is recommended as front-line and second-line treatment in those patients who attained a long progression-free survival (PFS) with the previous regimen. Bendamustine and rituximab (BR) is one of the most widely adopted CIT regimens, including second-line treatment. Unfortunately, durations of remission following BR combination therapy tend to be short in patients with heavily pre-treated disease or who have already received rituximab. The incorporation of a maintenance following induction chemotherapy to overcome the shorter remission durations in this population is a reasonable option.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-12-03
• Study First Submitted: 2019-01-15
• Study First Submitted QC: 2019-02-18
• Study First Posted: 2019-02-20
• Status Verified: 2019-12
• Primary Completion: 2019-12-03
• Last Update Submitted: 2020-01-14
• Last Update Posted: 2020-01-18
• Study Completion: 2020-12-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 112

Inclusion Criteria

• Confirmed diagnosis of CD20-positive CLL that meets the iwCLL criteria (Hallek et al, 2008).
• Relapsed or refractory status of disease after at least one prior chemotherapy regimen.
• ECOG performance status of 0-2 at study entry
• Patients have not received prior therapy with bendamustine
• Prior therapy with rituximab is permitted, even in the setting of rituximab refractory disease.

For inclusion in the research part of maintenance therapy (phase B):

• At least a partial response (PR or better; Hallek et al, 2008) must be achieved after induction of BR (phase A)

Exclusion Criteria

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent document or complying with the protocol treatment.
• Pregnant or breast-feeding females.
• Known to be positive for human immunodeficiency virus (HIV) or infectious hepatitis (type B or C).
• Patients are not eligible if there is a prior history or current evidence of central nervous system or leptomeningeal involvement.
• Richter syndrome or chronic prolymphocytic leukemia.
• Uncontrolled autoimmune hemolytic anemia or thrombocytopenia.
• Concurrent use of other anti-cancer agents or treatments.
• Laboratory test results within these ranges: ANC ≤ 1000/μL, Platelet count ≤ 75,000/μL.
• Total bilirubin Total bilirubin ≥ 2X upper limit laboratory normal (ULN). Patients with non-clinically significant elevations of bilirubin due to Gilbert's disease are not required to meet these criteria.
• Serum transaminases AST (SGOT) and ALT (SGPT) ≥ 3 x ULN, and/or serum alkaline phosphatase ≥ 5 X ULN.
• New York Heart Association class 3-4 heart failure.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Experimental: 6 cycles BR -> 4 x BR	BR as Maintenance	Induction plus BR as maintenance (N=56)

Primary Outcome Measures

Name	Time	Method
Progression-free survival	42 months	PFS is defined as the number of days from the date of first dose of any study drug (rituximab or bendamustine) to the date of disease progression or death, whichever occurs first. PFS will be compared with its proper historical control (BR as induction without subsequent maintenance).

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	60 months (6 months induction therapy, 12 months maintenance, 42 months long-term follow-up	OS is defined as number of days from the date of first dose of any study drug (rituximab or bendamustine) to the date of death.
Safety evaluations	Up to 30 months	To determine the safety and tolerability of induction chemotherapy and maintenance therapy separately for two groups as assessed by CTCAE v4.0:
Health Related Quality of Life (HRQoL)	Up to 30 months	To determinate the effect of maintenance therapy on HRQoL using the EORTC Core quality of life questionnaire (QOL-C30, version 3.0).
Overall Response Rate (ORR)	Approximately 24 months after initial dose of study drug.	ORR is defined as the proportion of participants with an overall response (CR, CRi, nodular partial remission \[nPR\] plus partial remission \[PR\]) per the 2008 Modified IWCLL NCI-WG criteria.

Trial Locations

Locations (1)

Semochkin Sergey; 🇷🇺 Moscow, Ostrovitianov Str. 1, Russian Federation