Study of Bendamustine/Rituxan Induction Chemotherapy With Revlimid Maintenance for Relapsed/Refractory CLL and SLL

Phase II Study of Bendamustine and Rituximab Induction Chemoimmunotherapy With Maintenance Lenalidomide and Rituximab in Relapsed/Refractory CLL/SLL

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00974233

Enrollment

Registered

2009-09-10

Start date

2009-10-31

Completion date

2015-04-30

Last updated

2019-12-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Keywords

CLL, SLL

Brief summary

The purpose of this research is to evaluate a new combination of chemotherapy drugs for CLL/SLL using the drugs bendamustine (an intravenous chemotherapy drug), rituximab (an intravenous medication called a monoclonal antibody), and lenalidomide (an anti-cancer pill). The purpose of this study is to see if giving the chemotherapy pill lenalidomide after treatment with bendamustine and rituximab is able to prolong the period of time before the cancer starts growing again and causing symptoms.

Interventions

DRUGBendamustine

90 mg/m2/day IV days 1 and 2 every 28 days for 6 cycles

DRUGRituximab

375 mg/m2 Day 1 every 28 days for 6 cycles

DRUGLenalidomide

5 mg/day days 1-28 of each 28 day cycle, up to 12 cycles maximum. Dose escalation to 10 mg/day allowed after one cycle as defined in the protocol.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Histologically confirmed,CLL/SLL, documented relapsed or refractory disease after at least one prior chemotherapy regimen. * In cases of SLL, patients must have at least one bidimensionally measurable lesion at least ≥1.5 cm measured in one dimension. * ECOG performance status of 0-2 at study entry * Laboratory test results within these ranges: ANC \<=1500/μL, Platelet count \<= 100,000/μL. Patients with ANC \<1500/μL or plt \<100,000/μL with splenomegaly or extensive bone marrow involvement as the etiology for their cytopenias are eligible. * creatinine clearance of \>60 mL/min as determined by the Cockcroft-Gault calculation. * 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) \<=5x ULN, Serum alkaline phosphatase ≤5 X ULN. * Disease free of prior malignancies for ≥ 2 years with the exception of basal or squamous cell skin carcinoma, carcinoma in situ of the breast or cervix, or localized prostate cancer (treated definitively with hormone therapy, radiotherapy, or surgery). * Patients may have received prior therapy with bendamustine or lenalidomide, but must not have disease that is refractory to bendamustine or lenalidomide. * Prior therapy with rituximab is permitted, even in the setting of rituximab refractory disease.

Exclusion criteria

* Has received \>5 lines of prior therapy for their disease. Re-treatment with an identical regimen does not count as a new regimen. * Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form or comply with the protocol treatment. * Pregnant or breast feeding females. Lactating females must agree not to breast feed while taking lenalidomide. * Prior history or current evidence of central nervous system or leptomeningeal involvement. * Use of any other experimental drug or therapy within 28 days of baseline. * Known hypersensitivity to thalidomide. * The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs. * Known to be positive for HIV or infectious hepatitis, type B or C.

Design outcomes

Primary

Measure	Time frame	Description
Progression Free Survival	42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)	The primary endpoint of this study was progression-free survival (PFS), defined as the number of days from the day of first study drug administration to the day the patient experienced disease progression or death from any cause. Response and progression in cases of small lymphocytic lymphoma(SLL) were evaluated using the International Working Group Criteria for response in NHL (Cheson, et al 1996). Response and progression in cases of chronic lymphocytic leukemia (CLL) were evaluated using the NCI-sponsored CLL Working Group guidelines for CLL (Cheson, et al 2007).
Progression-free Survival	42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)	Progression-free survival (PFS) is defined as the time from the day of first study drug administration until progression of CLL/SLL or death from any cause. PFS is reported as the proportion of participants with PFS up to 42 months.

Secondary

Measure	Time frame	Description
Objective Response Rate (Complete + Partial Responses)	42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)	Response and progression in cases of SLL were evaluated using the International Working Group Criteria for response in NHL (Cheson, et al 1996). Response and progression in cases of CLL were evaluated using the NCI-sponsored CLL Working Group guidelines for CLL (Cheson, et al 2007). Complete response defined as resolution enlarged lymph nodes, spleen and liver; normalization of blood counts (neutrophils, hemoglobin, platelets); no residual CLL/SLL detectable in the bone marrow. Partial response defined as 50% or more reduction in size of enlarged lymph nodes, liver or spleen; 50% or more improvement of blood counts; 50% or more improvement in the blood lymphocyte count. Progressive disease defined as 50% or more increase in the combined measurements of at least 2 lymph nodes as measured on CT scans or the appearance of new enlarged lymph nodes; 50% of more increase in the size of the spleen or liver; 50% or more increase in blood lymphocyte count.
Toxicities Observed With Induction Chemotherapy and Maintenance Therapy	42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)	Toxicities were reported using the Common Terminology Criteria for Adverse Events, version 3.0.
Overall Survival	42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)	Overall survival (OS) is defined as the time from the day of first study drug administration until death from any cause.

Countries

United States

Participant flow

Recruitment details

Research subjected from the University of Wisconsin and 7 Wisconsin Oncology Network institutions were enrolled from October 2009 to November 2011. Subjects were enrolled from outpatient hematology clinics at each participating institution.

Participants by arm

Arm	Count
Overall Study Population Patient population with chronic lymphocytic leukemia/small lymphocytic lymphoma with progressive disease in need of therapy after at least 1 prior chemotherapy regimen, but no more than 5 prior unique chemotherapy regimens (retreatment with identical regimen did not count as a unique regimen).	34
Total	34

Withdrawals & dropouts

Period	Reason	FG000
Induction Chemoimmunotherapy	Adverse Event	7
Induction Chemoimmunotherapy	Death	2
Induction Chemoimmunotherapy	Lack of Efficacy	5
Induction Chemoimmunotherapy	Withdrawal by Subject	1
Maintenance Lenalidomide	Adverse Event	8
Maintenance Lenalidomide	Lack of Efficacy	5

Baseline characteristics

Characteristic	Overall Study Population
Age, Continuous	67 years
Baseline cytogenetics 13q deletion	2 participants
Baseline cytogenetics 17p or 11q deletions	11 participants
Baseline cytogenetics Normal	3 participants
Baseline cytogenetics Trisomy 12	8 participants
Baseline cytogenetics Unknown	10 participants
Disease staging Ann Arbor 3/4 (SLL)	7 participants
Disease staging Ann Arbor stage 1/2 (SLL)	1 participants
Disease staging Rai stage 1/2 (CLL)	12 participants
Disease staging Rai stage 3/4 (CLL)	14 participants
ECOG performance status ECOG performance status 0-1	32 participants
ECOG performance status ECOG performance status 2	2 participants
Elevated serum lactate dehydrogenase (LDH) level Enrollment LDH elevated	20 participants
Elevated serum lactate dehydrogenase (LDH) level Enrollment LDH not elevated	14 participants
Median prior therapies	2 prior therapies
Prior therapy with fludarabine No previous fludrarabine exposure	11 participants
Prior therapy with fludarabine Prior fludarabine-based therapy	23 participants
Prior therapy with rituximab No prior therapy with rituximab	7 participants
Prior therapy with rituximab Prior therapy with rituximab	27 participants
Refractory to most recent therapy Not refractory to most recent therapy	30 participants
Refractory to most recent therapy Refractory to most recent therapy	4 participants
Sex: Female, Male Female	10 Participants
Sex: Female, Male Male	24 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	34 / 34	19 / 19
serious Total, serious adverse events	14 / 34	8 / 19

Outcome results

Primary

Progression-free Survival

Progression-free survival (PFS) is defined as the time from the day of first study drug administration until progression of CLL/SLL or death from any cause. PFS is reported as the proportion of participants with PFS up to 42 months.