Clinical trial NCT03847727: Bendamustine and Rituximab (BR) as Induction and Maintenance in Relapsed and Refractory Chronic Lymphocytic Leukemia
Official title: Study of Bendamustine and Rituximab as Induction Immunochemotherapy Followed by Maintenance Bendamustine and Rituximab in Relapsed and Refractory B-cell Chronic Lymphocytic Leukemia (CLL)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Chronic Lymphocytic Leukemia
Keywords: Chronic Lymphocytic Leukemia
Bendamustine Hydrochloride
Rituximab
Maintenance
Lead sponsor: Pirogov Russian National Research Medical University
Sponsor class: OTHER
First posted: 2019-02-20
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with relapsed or refractory CLL receiving treatment at the University Hematology Hospital and Ambulant clinic.

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free survival
timeFrame: 42 months
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Approximately 24 months after initial dose of study drug.
measure: Overall Survival (OS)
timeFrame: 60 months (6 months induction therapy, 12 months maintenance, 42 months long-term follow-up
measure: Safety evaluations
timeFrame: Up to 30 months
measure: Health Related Quality of Life (HRQoL)
timeFrame: Up to 30 months
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Semochkin Sergey
state: Ostrovitianov Str. 1
Study officials:
affiliation: Pirogov Russian National Research Medical University
name: Sergey Semochkin, Professor
role: PRINCIPAL_INVESTIGATOR
References: