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Chronic Lymphocytic LeukemiaPhase 1/2CLL2PNCT01558167

A Safety and Efficacy Trial of a Combination of Bendamustine, Rituximab and Lenalidomide in Patients With Chronic Lymphocytic Leukemia

A Phase 1/2 study testing Bendamustine, Rituximab, Lenalidomide in people with Chronic Lymphocytic Leukemia, run by German CLL Study Group at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a prospective, multicenter, open label, non-randomized, phase I/II-study to define safety and efficacy of BRL combination in relapsed/refractory patients and to recommend a safe and efficacious dose for future phase II/III study. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Lymphocytic Leukemia
What is being tested?
Bendamustine, Rituximab, Lenalidomide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
1 siteGermany
Study dates
Feb 2011to Jun 2015
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed written informed consent.
  • 18 years of age or older.
  • Medically fit patients without relevant comorbidity, defined as total CIRS score ≤ 6.
  • WHO performance status of 0-2.
  • Confirmed diagnosis of CLL in need of treatment (Binet C or A/B with active disease) according to the updated IWCLL guidelines (Hallek et al. 2008).
  • Life expectancy > 12 weeks.
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  • Relapsed or refractory disease after at least one, but no more than 3 prior regimens. Patients who previously received bendamustine (with or without rituximab) must have had at least a partial response with duration of response of at least six months.
  • CLL therapy, major surgery, or irradiation for CLL was completed > 4 weeks before registration in this study. Patients must have recovered from the acute side effects incurred as a result of previous therapy.
  • Patient is able and willing to receive adequate anticoagulation as specified in this protocol.
  • Adequate liver function as indicated by a total bilirubin, AST, and ALT ≤2 the institutional ULN value, unless directly attributable to the patient's tumor.
  • Creatinine clearance >60ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured after 24h-urine collection.
  • ANC > 1500/µl and platelet count > 75.000/μl, unless decrease is due to bone marrow involvement of CLL
  • Negative serological hepatitis B test, negative testing of hepatitis C RNA, negative HIV test within 6 weeks prior to registration.
  • Females of childbearing potential (FOCP) must understand that the study medication has a teratogenic risk and must agree to use, and be able to comply with effective contraception without interruption, 4 weeks before starting study drug, throughout study drug therapy (including dose interruptions) and for 6 months after the end of study drug therapy, even if she has amenorrhea. This applies unless the subject commits to absolute and continued abstinence confirmed on a monthly basis.

Who cannot join

  • Previously treated with > 3 prior regimens for CLL.
  • Known central nervous system (CNS) involvement of CLL.
  • Patients who have progressed with more aggressive B-cell cancers such as Richter's syndrome or are diagnosed with B-PLL.
  • History of anaphylaxis following exposure to any of the used study-drugs and/or thalidomide.
  • Evidence of TLS per the Cairo-Bishop definition of laboratory TLS (subjects may be enrolled upon correction of electrolyte abnormalities).
  • Participation in another clinical trial and/or use of investigational agents or concurrent anti cancer treatment within the last 4 weeks of registration.
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  • Other severe, concurrent diseases, including tuberculosis, mental disorders, serious cardiac functional capacity (class III or IV as defined by the New York Heart Association Classification), severe diabetes, severe hypertension, pulmonary disease (COPD with hypoxemia), or major organ malfunction that could interfere with the patient's ability to participate in the study.
  • Pregnant or lactating women.
  • Any circumstance at the time of study entry that would preclude completion of the study or the required follow-up.
  • Active secondary malignancy requiring treatment (except basal cell carcinoma or malignant tumor curatively treated by surgery) within the last 5 years before registration.
  • Active bacterial, viral or fungal infection.
  • Medical condition requiring prolonged use of oral corticosteroids (> 1 month).
  • Cerebral dysfunction, legal incapacity.
  • Patients with contraindications according to Summary of Product Characteristics or Investigator's Brochure.
  • Patients who are employees of the Sponsor (University of Cologne) or the study sites.
  • Persons placed in an institution by legal or official order.

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • University Hospital of Cologne

    Cologne, 50924

Other trials in Germany

About this study

Official title: A phaseI/II Safety and Efficacy Trial of a Combination of Bendamustine, Rituximab and Lenalidomide (BRL) in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

This is a prospective, multicenter, open label, non-randomized, phase I/II-study to define safety and efficacy of BRL combination in relapsed/refractory patients and to recommend a safe and efficacious dose for future phase II/III study.

Hypothesis: The simultaneous administration of BRL in relapsed CLL is feasible, safe and efficient.

Read the detailed description

As too its mechanism of action lenalidomide seems to work rather by immunomodulation than by a direct anti-proliferative activity against CLL cells. Lenalidomide stimulates T- and NK-cells, modulates the tumour microenvironment in CLL and inhibits bone marrow angiogenesis. There is a rationale to combine lenalidomide with the alpha-CD20 mAb rituximab because lenalidomide enhances NK cell mediated antibody dependent cytotoxicity of rituximab treated NHL cells. On the other hand, there is increasing evidence that the combination of chemotherapy (FC) and rituximab results in highest response rates and longest progression-free survival in treatment naive and relapsed CLL. Besides FCR the combination of bendamustine, a hybrid alkylating agent with properties of a purine-analogue, with rituximab (BR) seems to be very active in relapsed and treatment-naive CLL based on results of a phase II trial of the GCLLSG. Preliminary results with lenalidomide showed a promising response rate of 32% including high risk patients. Thus, the combination of BRL could improve the therapeutic activity in high risk CLL by combining two immunomodulatory with a classic cytotoxic principle.

Being tested
Bendamustine, Rituximab, Lenalidomide
Keywords
Dose limiting toxicity of Lenalidomide, Chronic lymphocytic leukemia
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bendamustine, Rituximab, LenalidomideDrug

    Also called Ribomustine, MabThera, Revlimid

    Bendamustine: 50 mg/m2, i.v., day 1+2

    Rituximab: Cycle 1: 375 mg/m2, i.v. day 0; Cycle 2-6: 500mg/m2, i.v., day 1

    Lenalidomide:

    • Dose level 1: Cycle 1-6: 2,5mg p.o., d1-28
    • Dose level 2: Cycle 1: 2,5mg p.o., d1-28; Cycle 2-6: 5mg p.o., d1-28
    • Dose level 3: Cycle 1: 2,5mg p.o., d1-28; Cycle 2:5mg p.o., d1-28; Cycle 3-6: 10 mg p.o., d1-28
    • Dose level 4: Cycle 1: 2,5mg p.o., d1-28; Cycle 2:5mg p.o., d1-28; Cycle 3: 10 mg p.o.,d1-28, Cycle 4-6: 15 mg p.o.,d1-28
    • Dose level 5: maximal tolerated dose
Study groups in NCT01558167
Study groupRoleWhat they receive
Bendamustine, Rituximab,LenalidomideExperimentalDose modification treatment plan of lenalidomide
Receives: Drug: Bendamustine, Rituximab, Lenalidomide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. dose limiting toxicity

    DLT defined as

    • absolute neutrophil count < 500/µl for 7 consecutive days or more
    • febrile neutropenia
    • platelet count < 20.000/µl
    • grade 4 tumour flare
    • grade 4 non-hematologic toxicity

    Measured: After 28 days of dosing at the respective target dose level of lenalidomide

Secondary outcomes (3)

  1. Response rate

    response will be evaluated according to criteria of the CLL-Guidelines on CLL of the IWCLL-working Group.

    Measured: up to 4 years

  2. progression free survival

    Progression-free survival based on investigator's assessment:

    PFS is defined as the time from registration to the first occurrence of progression, relapse or death from any cause. Disease progression will be assessed by the investigators using the IWCLL criteria.

    Measured: up to 4 years

  3. Overall Survival

    Overall survival is defined as the time from registration to death.

    Measured: up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Mar 2012 (estimated)
  2. Study startFeb 2011
  3. Primary completionOct 2013
  4. Study completionJun 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01558167
Sponsor's protocol ID
CLL2P
Other IDs
2009-012957-39, 2009
Acronym
CLL2P
Status last verified
May 2018
First submitted
19 May 2011
Last updated
15 May 2018
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Maurer C, Pflug N, Bahlo J, Kluth S, Rhein C, Cramer P, Gross-Ophoff C, Langerbeins P, Fink AM, Eichhorst B, Kreuzer KA, Fischer N, Tausch E, Stilgenbauer S, Bottcher S, Dohner H, Kneba M, Dreyling M, Binder M, Hallek M, Wendtner CM, Bergmann M, Fischer K; German CLL Study Group. Bendamustine and rituximab in combination with lenalidomide in patients with chronic lymphocytic leukemia. Eur J Haematol. 2016 Sep;97(3):253-60. doi: 10.1111/ejh.12714. Epub 2016 Feb 9.

    PubMed 26643449

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Bendamustine, Rituximab, Lenalidomide in people with Chronic Lymphocytic Leukemia, run by German CLL Study Group at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 May 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

dose limiting toxicity (time frame: After 28 days of dosing at the respective target dose level of lenalidomide). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01558167, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2018.

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