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CLLPhase 1/2NCT01703364

Fludarabine/Rituximab Combined With Escalating Doses of Lenalidomide in Untreated CLL

A Phase 1/2 study testing Lenalidomide in people with CLL and Chronic Lymphocytic Leukemia, run by Arbeitsgemeinschaft medikamentoese Tumortherapie at 2 sites in Austria.

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 trial in patients with previously untreated CLL. Eligible patients will receive Lenalidomide with a backbone of Fludarabine and Rituximab for 6 therapy cycles. Lenalidomide will be increased by dose steps of 5 mg every cycle in the absence of limiting toxicity. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
CLL, Chronic Lymphocytic Leukemia
What is being tested?
Lenalidomide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
2 sitesAustria
Study dates
Jun 2012to Oct 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
  • Male or female ≥ 18 years of age
  • CLL (as determined by CD23+, CD5+, CD19+)
  • Treatment indication as defined by the NCI Workshop criteria (see appendix 6 and reference 10)
  • ECOG ≤ 2
  • No previous treatment of the CLL by chemotherapy, radiotherapy (except localized radiotherapy of 1 lymphatic area) or immunotherapy
  • Life expectancy > 6 months (except prognosis due to high risk CLL)

Who cannot join

  • Active bacterial, viral or fungal infection
  • Positivity for HIV, Hepatitis B or C
  • Patients with known history of thromboembolic events
  • Reduced organ functions and bone marrow dysfunction not due to CLL
  • Creatinine clearance of below 30 ml/min
  • Patients with known history of thromboembolic events
Show all 16Show fewer
  • Patients with a history of other malignancies within 2 years prior to study entry (except for adequately treated carcinoma in situ of the cervix; basal or squamous cell skin cancer; low grade, early stage localized prostate cancer treated surgically with curative intent; good prognosis DCIS of the breast treated with lumpectomy alone with curative intent)
  • Patients with medical co-morbid conditions that would require long term use (> 1 month) of systemic corticosteroids during study treatment
  • Patients with a history of severe cardiac disease; e.g. NYHA Functional Class III or IV heart failure, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, or unstable angina
  • Other known co-morbidity with the potential to dominate survival
  • Transformation to aggressive B-cell malignancy (e.g., large B-cell lymphoma, Richter's syndrome, or prolymphocytic leukemia (PLL))
  • Hypersensitivity with anaphylactic reaction to humanised monoclonal antibodies or any of the applied drugs
  • Concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy not indicated in the study protocol
  • Administration of any investigational agent(s) within 4 weeks prior to entry
  • Pregnancy or lactation
  • Medical or psychological condition which in the opinion of the Investigator would not permit the patient to complete the study or sign meaningful informed consent

Trial locations and contacts

2 sites in 1 country.

Austria2 sites

  • Universitätsklinik für Innere Medizin Innsbruck, Klinische Abteilung für Hämatologie und Onkologie

    Innsbruck, Tyrol, 6020

  • Universitätsklinik der PMU Salzburg, Univ-Klinik für Innere Medizin III

    Salzburg, State of Salzburg, 5020

Other trials in Austria

About this study

Official title: Fludarabine/Rituximab Combined With Escalating Doses of Lenalidomide in Untreated Chronic Lymphocytic Leukemia (CLL) - a Dose-finding Study With Escalating Starting Dose of Lenalidomide and Concomitant Evaluation of Safety and Efficacy

This is a trial in patients with previously untreated CLL. Eligible patients will receive Lenalidomide with a backbone of Fludarabine and Rituximab for 6 therapy cycles. Lenalidomide will be increased by dose steps of 5 mg every cycle in the absence of limiting toxicity. If limiting toxicity ensues the patients will be treated with last tolerable dose for the remainder of the 6 treatment cycles.

The first 5 patients will start with dose level 5 mg Lenalidomide and further escalating dose. After the fifth patient is included in the study, enrolment will be interrupted until this patient has finished his first treatment cycle. A safety board will evaluate the toxicities of the first 5 patients. If there are more than 2 patients experiencing a dose limiting toxicity (DLT) in the first treatment cycle, the starting dose will not be escalated and further 5 patients will be enrolled with a starting dose of 5 mg Lenalidomide. If only 2 or less patients experience a DLT in the first treatment cycle, the next 5 patients will start the treatment with 10 mg Lenalidomide.

Read more

The rational for the higher starting doses stems from the lack of tumor lysis or tumor flare toxicity in this combination on the one hand and from the observation that the very slow escalation from 2,5 mg on led to a lack of efficacy in monotherapy trials due to early progression in a relevant number of cases. The increase of the Lenalidomide dosage should result in an increased efficacy especially at the beginning and a higher cumulative dose of Lenalidomide.

The identification of patients intolerant to Lenalidomide by immunophenotyping of the T cells for validation is also part of this trial, because intolerance seems to be not dose dependent but may be caused by T cell activation. Therefore, early identification of patients intolerant to this form of modern immunochemotherapy and establishing efficient Lenalidomide based combination therapy is an important part of improvement of current CLL treatment.

Being tested
Lenalidomide
Keywords
CLL, Lenalidomide, Revlimid, AGMT, T cell
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.

  • LenalidomideDrug

    Also called Revlimid

    Lenalidomide: day 8-21 of cycle 1 and day 1-21 of cycles 2-6; Starting Dose: 5 mg (first 5 patients) and 10 mg (further 5 patients) increase Lenalidomide dose via dose levels (10)/15/20/25 mg/d every 28 days if no limiting toxicity occurs

    Fludarabine: 25 mg/m2 iv d1-3 or 40 mg/m2 po d1-3; repeat every 28 days

    Rituximab: 375 mg/m2 iv day 4 on cycle 1 and 500 mg/m2 iv day 1 on cycles 2-6; repeat every 28 days

Study groups in NCT01703364
Study groupRoleWhat they receive
Lenalidomide/Fludarabine/RituximabExperimentalLenalidomide: day 8-21 of cycle 1 and day 1-21 of cycles 2-6; Starting Dose: 5 mg (first 5 patients) and 10 mg (further 5 patients) increase Lenalidomide dose via dose levels (10)/15/20/25 mg/d every 28 days if no limiting toxicity occurs Fludarabine: 25 mg/m2 iv d1-3 or 40 mg/m2 po d1-3; repeat every 28 days Rituximab: 375 mg/m2 iv day 4 on cycle 1 and 500 mg/m2 iv day 1 on cycles 2-6; repeat every 28 days
Receives: Drug: Lenalidomide

What is being measured

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

  1. Tolerability of escalated starting dose

    Interim analysis after completion of cylce 1 of the first 5 patients, final analysis after last pastient last visit Metrics: Number of patients experiencing defined dose limiting toxicities during cycle 1

    Measured: 12 month, 20 month

Secondary outcomes (6)

  1. Establishment of maximal tolerated dose (MTD) of Lenalidomide in combination with FR

    Measured: 20 month

  2. Time to MTD

    Measured: 20 month

  3. Safety profile of the FRL combination

    Analysis of occuring adverse events during the study treatment according to Common Terminology Criteria for Adverse Events (CTCAE)

    Measured: 20 month

  4. Response rates in all phases by 4-colour flow cytometric and ASO-PCR MRD analysis

    Measured: 20 month

  5. Risk factor analysis (FISH cytogenetics, CD38/ZAP-70 expression, mutation status)

    Measured: 20 month

  6. Longitudinal definition of T cell subsets (including prognostic EM T cells and Treg cells)+/- PD1

    Measured: 20 month

Timeline

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

  1. First posted10 Oct 2012 (estimated)
  2. Study startJun 2012
  3. Primary completionMar 2015
  4. Study completionOct 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
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01703364
Sponsor's protocol ID
AGMT_CLL-9
Other IDs
2011-004912-43
Status last verified
May 2016
First submitted
4 Oct 2012
Last updated
26 May 2016
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Lenalidomide in people with CLL and Chronic Lymphocytic Leukemia, run by Arbeitsgemeinschaft medikamentoese Tumortherapie at 2 sites in Austria.

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 7 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 26 May 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Austria. 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?

Tolerability of escalated starting dose (time frame: 12 month, 20 month). 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 NCT01703364.

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 26 May 2016.

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