Chronic Lymphocytic LeukemiaPhase 2NCT01199575
Phase II Trial of Revlimid® and Rituximab for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
A Phase 2 study testing Revlimid and Rituximab in people with Chronic Lymphocytic Leukemia and CLL, run by University of California, San Diego at 1 site in United States.
Trial summary
The Chronic Lymphocytic Leukemia (CLL) Research Consortium (CRC) is conducting a two-arm, multi-center phase II trial of Revlimid® and rituximab for Relapsed or Refractory CLL for patients under the age of 65 and patients 65 years and older. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia, CLL
- What is being tested?
- Revlimid and Rituximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2010to 19 Jul 2022
- Phase
- Phase 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
- Diagnosis of chronic lymphocytic leukemia (CLL).
- Subjects must have active disease appropriate for therapy.
- Previous treatment for CLL
- Understand and voluntarily sign an informed consent form.
- Age ≥18 years at the time of signing the informed consent form.
- Able to adhere to the study visit schedule and other protocol requirements.
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- ECOG performance status of ≤ 2 at study entry (see Appendix B).
- Laboratory test results within these ranges: Absolute neutrophil count ≥ 1.0 x 109/L,Platelet count ≥ 50 x 109/L, Total bilirubin ≤ 1.5 mg/dL, AST (SGOT) and ALT (SGPT) ≤ 2 x ULN, Creatinine clearance estimated to be ≥ 30 ml/min
- Disease free of prior malignancies for ≥ 2 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in situ" of the cervix or breast.
- 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 Revlimid® 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 Revlimid®. 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 had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. See Appendix: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods, AND also Appendix: Education and Counseling Guidance Document.
Who cannot join
- Known Hepatitis B Ag positive, Hepatitis C positive patients.
- Known HIV positive patients.
- Patients with uncontrolled Autoimmune Hemolytic Anemia (AIHA) or autoimmune thrombocytopenia (ITP).
- Inability to provide informed consent.
- Concurrent malignancy (excluding basal and squamous cell skin cancers).
- Active fungal, bacterial, and/or viral infection.
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- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
- Pregnant or breast-feeding females. (Lactating females must agree not to breast feed while taking Revlimid®).
- Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
- 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.
- Concurrent use of other anti-cancer agents or treatments.
- Patients with history of deep venous thrombus or pulmonary embolism. Patients who are at increased risk of thrombosis during treatment with Revlimid® including those taking concurrent erythropoietin, darbepoetin or high-dose corticosteroids are also excluded.
- Patients with a history of embolic events (e.g. TIA) from arrhythmia or peripheral arterial disease or of recent mycocardial infarction whether or not treated with anti-platelet drugs.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Diego
La Jolla, California, 92093
About this study
Official title: A Phase II Trial of Revlimid® and Rituximab, for the Treatment of Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
The Chronic Lymphocytic Leukemia (CLL) Research Consortium (CRC) is conducting a two-arm, multi-center phase II trial of Revlimid® and rituximab for Relapsed or Refractory CLL for patients under the age of 65 and patients 65 years and older.
Lenalidomide (Revlimid) is an immunomodulatory agent with promising clinical activity in CLL and is FDA approved for treatment of relapsed multiple myeloma and 5q-myelodysplastic syndrome. Rituximab (Rituxan) is a monoclonal antibody to CD20 that is approved for the treatment of CLL.
The primary objective of this study is to determine the overall response rate of the combination of Revlimid® and rituximab in previously treated CLL patients. All patients will receive treatment with Revlimid® starting at a low dose that will be dose escalated based on individual patient tolerability. The combination of Revlimid and Rituximab will be administered for a maximum of 7 cycles. Patients with residual leukemia following seven cycles of treatment with the combination may elect to continue on protocol for an additional 6 cycles of single agent Revlimid® consolidation.
Read the detailed description
The Chronic Lymphocytic Leukemia (CLL) Research Consortium (CRC) is conducting a two-arm, multicenter phase II trial of Revlimid® and rituximab for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) for patients under the age of 65 and patients 65 years and older.
Revlimid® (lenalidomide) a derivative of thalidomide with immune-modulating properties. Revlimid® is FDA approved for treatment of relapsed multiple myeloma and 5q- myelodysplastic syndrome. Revlimid® has promising clinical activity, in both previously treated and treatment naive CLL in early clinical trials. However, the mechanism(s) whereby Revlimid® is active in CLL is unknown. Rituximab (Rituxan®) is a monoclonal antibody that binds to CD20 expressed on normal and leukemia B cells. Rituximab is approved for the treatment of CLL.
In preclinical models of lymphoma Revlimid improved the activity of Rituximab. In clinical studies of relapsed and/or refractory CLL the combination Revlimid and Rituximab was associated with better therapeutic effects compared with what was historically observed with either agent alone.
The purpose of this study is to evaluate the safety and activity of the combination of Revlimid® and rituximab in relapsed or refractory CLL, elucidate the mechanism of action of Revlimid® in CLL, and to assess whether prognostic factors might predict those patients likely to benefit from this therapy in the future.
The primary objective of this study is to determine the overall response rate (ORR) of the combination of Revlimid® and rituximab in previously treated CLL patients for those age 65 years and above and those younger than 65.
Secondary objectives will evaluate the safety of the combination of Revlimid® and Rituximab, response duration, improvement in hematologic parameters, activity of the combination in high-risk CLL subsets, the significance of the tumor flare reaction and to compare the activity of this regimen when administered to previously treated patients to our protocol in the front line setting and to compare these outcomes for both arms of the study.
All patients will receive treatment with Revlimid® starting at a low dose that will be slowly dose escalated based on individual patient tolerability. The combination of Revlimid and Rituximab will be administered for a maximum of 7 cycles. Patients with residual leukemia following seven cycles of treatment with the combination may elect to continue on protocol for an additional 6 cycles of single agent Revlimid® consolidation.
All patients will have baseline assessment of known CLL prognostic factors through the CRC tissue core. These known prognostic features in CLL together with novel prognostic factors will be evaluated for the ability to predict response to treatment with Revlimid® and the combination of Revlimid® and Rituximab.
- Conditions
- Chronic Lymphocytic Leukemia, CLL
- Being tested
- Revlimid, Rituximab
- Keywords
- Chronic Lymphocytic Leukemia, CLL, Relapsed or Refractory, previously treated
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RevlimidDrug
Also called lenalidomide
RituximabDrug
Also called Rituxan
| Study group | Role | What they receive |
|---|---|---|
| Revlimid + Rituximab | Experimental | A: Lenalidomide starting at a low dose 2.5 or 5 mg, 21 days/cycle escalated based on patient tolerability. Rituximab at 375mg/m2 administered following the first 21 days of lenalidomide monotherapy, continued weekly throughout cycle 2, and then every 4 weeks for subsequent cycles (3-7). Each patient may receive up to 7 cycles of treatment with the combination lenalidomide/rituximab if no progressive disease or significant toxicity. Patients with residual disease can elect to receive 6 additional cycles of single agent Revlimid as consolidation.
Each patient may receive up to a maximum of 13 cycles of treatment if no progressive disease or significant toxicity. Receives: Drug: Revlimid; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR)
Measured: nine months
Secondary outcomes (5)
Adverse Events to Study Treatment
Measured: one year
Progression Free Survival.
Measured: 2 years
Conversion of MRD-positive Complete Response or Partial Response (PR) to a MRD-negative Complete Response (CR) or Complete Response (CR) Respectively Following an Additional 6 Cycles of Revlimid Consolidation
Measured: 13 cycles
Overall Survival
Measured: 4 years
Treatment Free Survival.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2010 (estimated)
- Study startAug 2010
- Primary completionJan 2015
- Study completion19 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene Corporation
- Responsible party
- Principal investigator, Thomas Kipps, University of California, San Diego
- Investigators
- Thomas J Kipps, MD, PhD, Study director, Director of the CLL Research Consortium and University of California San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01199575
- Sponsor's protocol ID
- CRC022
- Status last verified
- Jul 2024
- First submitted
- 31 Aug 2010
- Last updated
- 15 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Revlimid® and Rituximab, for the Treatment of Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
- ClinicalTrials.gov ID
- NCT01199575
- Acronym / sponsor ID
- CRC022
- Conditions
- Chronic Lymphocytic Leukemia, CLL
- Keywords
- Chronic Lymphocytic Leukemia, CLL, Relapsed or Refractory, previously treated
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- Celgene Corporation
- Study start
- Aug 2010 (actual)
- Primary completion
- Jan 2015 (actual)
- Study completion
- 19 Jul 2022 (actual)
- First posted
- 13 Sep 2010 (estimated)
- Results
- Posted 23 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Chronic Lymphocytic Leukemia (CLL) Research Consortium (CRC) is conducting a two-arm, multi-center phase II trial of Revlimid® and rituximab for Relapsed or Refractory CLL for patients under the age of 65 and patients 65 years and older.
Lenalidomide (Revlimid) is an immunomodulatory agent with promising clinical activity in CLL and is FDA approved for treatment of relapsed multiple myeloma and 5q-myelodysplastic syndrome. Rituximab (Rituxan) is a monoclonal antibody to CD20 that is approved for the treatment of CLL.
The primary objective of this study is to determine the overall response rate of the combination of Revlimid® and rituximab in previously treated CLL patients. All patients will receive treatment with Revlimid® starting at a low dose that will be dose escalated based on individual patient tolerability. The combination of Revlimid and Rituximab will be administered for a maximum of 7 cycles. Patients with residual leukemia following seven cycles of treatment with the combination may elect to continue on protocol for an additional 6 cycles of single agent Revlimid® consolidation.
Detailed description
The Chronic Lymphocytic Leukemia (CLL) Research Consortium (CRC) is conducting a two-arm, multicenter phase II trial of Revlimid® and rituximab for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) for patients under the age of 65 and patients 65 years and older.
Revlimid® (lenalidomide) a derivative of thalidomide with immune-modulating properties. Revlimid® is FDA approved for treatment of relapsed multiple myeloma and 5q- myelodysplastic syndrome. Revlimid® has promising clinical activity, in both previously treated and treatment naive CLL in early clinical trials. However, the mechanism(s) whereby Revlimid® is active in CLL is unknown. Rituximab (Rituxan®) is a monoclonal antibody that binds to CD20 expressed on normal and leukemia B cells. Rituximab is approved for the treatment of CLL.
In preclinical models of lymphoma Revlimid improved the activity of Rituximab. In clinical studies of relapsed and/or refractory CLL the combination Revlimid and Rituximab was associated with better therapeutic effects compared with what was historically observed with either agent alone.
The purpose of this study is to evaluate the safety and activity of the combination of Revlimid® and rituximab in relapsed or refractory CLL, elucidate the mechanism of action of Revlimid® in CLL, and to assess whether prognostic factors might predict those patients likely to benefit from this therapy in the future.
The primary objective of this study is to determine the overall response rate (ORR) of the combination of Revlimid® and rituximab in previously treated CLL patients for those age 65 years and above and those younger than 65.
Secondary objectives will evaluate the safety of the combination of Revlimid® and Rituximab, response duration, improvement in hematologic parameters, activity of the combination in high-risk CLL subsets, the significance of the tumor flare reaction and to compare the activity of this regimen when administered to previously treated patients to our protocol in the front line setting and to compare these outcomes for both arms of the study.
All patients will receive treatment with Revlimid® starting at a low dose that will be slowly dose escalated based on individual patient tolerability. The combination of Revlimid and Rituximab will be administered for a maximum of 7 cycles. Patients with residual leukemia following seven cycles of treatment with the combination may elect to continue on protocol for an additional 6 cycles of single agent Revlimid® consolidation.
All patients will have baseline assessment of known CLL prognostic factors through the CRC tissue core. These known prognostic features in CLL together with novel prognostic factors will be evaluated for the ability to predict response to treatment with Revlimid® and the combination of Revlimid® and Rituximab.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Revlimid + Rituximab | Experimental | Drug: Revlimid, Drug: RituximabA: Lenalidomide starting at a low dose 2.5 or 5 mg, 21 days/cycle escalated based on patient tolerability. Rituximab at 375mg/m2 administered following the first 21 days of lenalidomide monotherapy, continued weekly throughout cycle 2, and then every 4 weeks for subsequent cycles (3-7). Each patient may receive up to 7 cycles of treatment with the combination lenalidomide/rituximab if no progressive disease or significant toxicity. Patients with residual disease can elect to receive 6 additional cycles of single agent Revlimid as consolidation. Each patient may receive up to a maximum of 13 cycles of treatment if no progressive disease or significant toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Diagnosis of chronic lymphocytic leukemia (CLL).
- Subjects must have active disease appropriate for therapy.
- Previous treatment for CLL
- Understand and voluntarily sign an informed consent form.
- Age ≥18 years at the time of signing the informed consent form.
Key exclusion criteria (15 listed)
- Known Hepatitis B Ag positive, Hepatitis C positive patients.
- Known HIV positive patients.
- Patients with uncontrolled Autoimmune Hemolytic Anemia (AIHA) or autoimmune thrombocytopenia (ITP).
- Inability to provide informed consent.
- Concurrent malignancy (excluding basal and squamous cell skin cancers).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RevlimidAlso: lenalidomide | Drug | Revlimid + Rituximab |
| RituximabAlso: Rituxan | Drug | Revlimid + Rituximab |
Primary outcome
Overall Response Rate (ORR)
Time frame: nine months
5 secondary outcomes
Adverse Events to Study Treatment
Time frame: one year
Progression Free Survival.
Time frame: 2 years
Conversion of MRD-positive Complete Response or Partial Response (PR) to a MRD-negative Complete Response (CR) or Complete Response (CR) Respectively Following an Additional 6 Cycles of Revlimid Consolidation
Time frame: 13 cycles
Overall Survival
Time frame: 4 years
Treatment Free Survival.
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Website for the CLL Research ConsortiumLink provided by the sponsor.
- Moore's UCSD Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas J Kipps, MD, PhD study director
Director of the CLL Research Consortium and University of California San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Revlimid and Rituximab in people with Chronic Lymphocytic Leukemia and CLL, run by University of California, San Diego at 1 site 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 10 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 15 Aug 2024. 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 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 phase mean?
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 23 Oct 2018). 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?
Overall Response Rate (ORR) (time frame: nine months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Aug 2024.