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Chronic Lymphocytic LeukemiaPhase 1/2NCT00536341

Fludarabine, Rituximab, and Lenalidomide in Minimally Treated/Untreated Patients With Chronic Lymphocytic Leukemia (CLL)

A Phase 1/2 study testing lenalidomide, Rituximab and Fludarabine in people with Chronic Lymphocytic Leukemia, run by SCRI Development Innovations, LLC at 6 sites in United States.

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 phase I/II trial will combine fludarabine, rituximab, and lenalidomide in untreated or minimally treated (Phase I only) CLL patients, employing fixed doses of fludarabine and rituximab, using a schedule similar to that examined by investigators at MD Anderson (J Clin Oncol 23(18):4079-88, 2005). 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?
lenalidomide, Rituximab and Fludarabine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
64 participants
Where
6 sitesUnited States
Study dates
Jan 2008to Nov 2016
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Understand and voluntarily sign an informed consent form.
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Age >=18 years at the time of signing the informed consent form.
  • Patient must have histopathologically confirmed B-cell CLL
  • For Phase I only: Untreated or minimally treated patients (patients who have received only prior single agent rituximab) are eligible. For those patients who have had rituximab monotherapy, last dose must be greater than 90 days prior to beginning study treatment.
  • For Phase II only: Untreated B-cell CLL patients only.
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  • Rai staging, will be employed. Patients must have Rai stage III/IV disease (irrespective of symptoms) OR symptomatic Rai stage 0-II disease, requiring therapy as defined by NCI 1996 guidelines.
  • Platelets must be > 75,000/mm3 and absolute neutrophil count must be > 1000/mm3 within 14 days of starting protocol treatment unless treating physicians deems the neutropenia is related to marrow involvement and then ANC > 750/mm3 is allowed.
  • Serum creatinine <=2.0 mg/dl obtained within 14 days of starting protocol treatment. Creatinine clearance as determined by the Cockroft-Gault formula, using ideal body weight, must be > 30 mL/minute.
  • AST or ALT must be < 3 x the upper limit of normal within 14 days of starting treatment.
  • ECOG performance of 0, 1 or 2.
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
  • Disease free of prior malignancies for >= 2 years (including carcinoma in situ of the cervix or breast) treated with curative intent and anticipated 5 year disease-free survival is greater than 90%. Any basal cell or squamous cell carcinoma of the skin treated with curative intent is permitted.
  • Able to take aspirin (325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use low molecular weight heparin).

Who cannot join

  • Major surgery less than 28 days prior to study treatment.
  • Any prior use of lenalidomide or thalidomide.
  • Concurrent use of other anti-cancer therapies.
  • Pregnant or breast feeding females. (Lactating females may be considered if they agree not to breast feed while receiving study treatment and until 12 months following last dose of rituximab).
  • History of pulmonary embolus or deep vein thrombosis.
  • Clinically significant heart dysfunction, defined as New York Heart Association class III or IV, at the time of screening, or history of myocardial infarction or heart failure within 6 months preceding the first study treatment (cardiac ejection fraction must be >= 50% within 8 weeks of beginning study treatment for any patient with a history of clinically significant heart dysfunction).
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  • Known positive for HIV, hepatitis B surface Ag, hepatitis B core antibody, or hepatitis C. Mandatory testing is not required, but should be considered in patients deemed high risk or suspicious.
  • Active infection requiring oral or intravenous antibiotics at study entry. After infection resolves patient may be evaluated for enrollment.
  • Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
  • Richter's transformation.
  • CNS involvement.
  • Other severe, acute, or chronic medical or psychiatric condition, laboratory abnormality, or difficulty complying with protocol requirements that may increase the risk associated with study participation or study drug administration or may interfere with interpretation of study results that in the judgment of the investigator would make the patient inappropriate for this study or that would prevent the patient from signing the informed consent form.
  • Use of any other biologic agent or disease-modifying anti-rheumatic drugs (DMARDS).
  • Known anaphylaxis or IgE-mediated hypersensitivity to murine proteins or any component of rituximab.
  • Evidence of laboratory TLS by Cairo-Bishop criteria (subjects may be enrolled upon correction of electrolyte abnormalities).

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Center for Cancer and Blood Disorders

    Bethesda, Maryland, 20817

  • National Capital Clinical Research Consortium

    Bethesda, Maryland, 20817

  • South Carolina Oncology Associates, PA

    Columbia, South Carolina, 29210

  • Florida Cancer Specialists

    Fort Myers, Florida, 33901

  • Tennessee Oncology, PLLC

    Nashville, Tennessee, 37023

  • Florida Hospital Cancer Institute

    Orlando, Florida, 32804

Other trials in United States

About this study

Official title: A Phase I/II Study of Fludarabine, Rituximab, and Lenalidomide in Minimally Treated and Untreated Patients With Chronic Lymphocytic Leukemia

This phase I/II trial will combine fludarabine, rituximab, and lenalidomide in untreated or minimally treated (Phase I only) CLL patients, employing fixed doses of fludarabine and rituximab, using a schedule similar to that examined by investigators at MD Anderson (J Clin Oncol 23(18):4079-88, 2005). Given that the optimal dose and schedule is not currently known, this trial will perform a phase I component followed by a phase II examination to further explore this regimen's activity.

Read the detailed description

While progress has been made in treating CLL patients over the last decade, a cure remains elusive for many patients treated with standard therapies. The combination of fludarabine, a purine analog, and rituximab, a monoclonal antibody, is an effective and frequently used therapy for CLL. However, this drug combination is associated with increased toxicity. Lenalidomide has been shown to be less toxic and has been used to treat hematologic malignancies including CLL. We propose this Phase I/Phase II study to examine the combination of lenalidomide with a rituximab/fludarabine backbone.

Keywords
Chronic Lymphocytic Leukemia, untreated, minimally treated, fludarabine, rituximab, lenalidomide
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

    2.5 mg orally (PO) daily, Days 8-28, Cycle 1; 5.0 mg PO daily, Days 8-28 Cycles 2-6

  • RituximabDrug

    Also called Rituxan

    375 mg/m2 Cycle 1 (split over Day 1 \& Day 2); 500 mg/m2 Day 1 of Cycles 2-6

  • FludarabineDrug

    Also called Fludara

    25 mg/m2 on Days 1, 2, and 3

Study groups in NCT00536341
Study groupRoleWhat they receive
lenalidomide, fludarabine, rituximabExperimentalPhase I Non-stratified, dose-escalation: >=3 patients per dose level. Safety and tolerability will be evaluated every 2 weeks during the active treatment. Doses of lenalidomide will be escalated, while the fludarabine and rituximab doses remain fixed. Phase II The Phase II regimen will be chosen following a review of the Phase I data. Following selection of the Phase II schedule, 40 treatment naive patients will be enrolled and treated with the Phase II regimen every 28 days for up to 6 courses. For those patients achieving a CR after 3 cycles, one additional cycle of treatment will be administered beyond CR confirmation.
Receives: Drug: lenalidomide; Drug: Rituximab; Drug: Fludarabine

What is being measured

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

  1. Number of Adverse Events as a Measure of Safety and Tolerability

    Recorded from first treatment until 30 days after last treatment and assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    Measured: 63 months

  2. Complete Response Rate

    An improvement in complete response to at least 60% following treatment, assessed using CT scans, clinical/lab examinations, and bone marrow aspirations, as defined by National Cancer Institute Working Group Response Criteria.

    Measured: At 12 weeks during treatment and 2 months post-treatment until disease progression, projected 8 months

Secondary outcomes (2)

  1. Progression-Free Survival

    Measured from first treatment to disease progression and assessed using Kaplan-Meier methods.

    Measured: Every 3 months during treatment until disease progression and every 6 months thereafter, up to 5 years

  2. Overall Survival

    Defined as the time from Day 1 of treatment administration to date of death from any cause, estimated using Kaplan-Meier methods.

    Measured: Every 3 months until treatment discontinuation, expected average of 6 months and then every 6 months thereafter up to 5 years

Timeline

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

  1. First posted27 Sep 2007 (estimated)
  2. Study startJan 2008
  3. Primary completionApr 2013
  4. Study completionNov 2016

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
64 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00536341
Sponsor's protocol ID
SCRI CLL 02
Status last verified
Nov 2016
First submitted
24 Sep 2007
Last updated
16 Jan 2017
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing lenalidomide, Rituximab and Fludarabine in people with Chronic Lymphocytic Leukemia, run by SCRI Development Innovations, LLC at 6 sites in United States.

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 15 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 16 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. 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?

Yes. Results are posted in the registry (first posted 4 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Adverse Events as a Measure of Safety and Tolerability (time frame: 63 months). The study lists 2 primary outcomes in all. 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 NCT00536341.

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 16 Jan 2017.

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