Chronic Lymphocytic LeukemiaPhase 1LLC-LENAR-08NCT01185262
Activity & Safety Study of Lenalidomide & Rituximab as Non-chemotherapy Based Therapy on Chronic Lymphocytic Leukemia
A Phase 1 study testing Lenalidomida and Rituximab in people with Chronic Lymphocytic Leukemia, run by MD Anderson International Spain SA at 7 sites in Spain.
Trial summary
The rationale for combining lenalidomide with rituximab derives from preclinical observations suggesting that lenalidomide may enhance the ADCC (antigen-dependent cellular cytotoxicity) triggered by monoclonal antibodies such as rituximab. 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?
- Lenalidomida and Rituximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 7 sitesSpain
- Study dates
- Apr 2009to Sep 2013
- Phase
- Phase 1
- 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
- Recurrent and refractory CLL patients that have received at least one previous treatment with purine analogs.
- Adequate liver function and renal function.
- ECOG performance status ≤ 2.
- Signed informed consent
- Male and female patients who are fertile agree to use an effective barrier method of birth control to avoid pregnancy.
Who cannot join
- Positive serological markers for hepatitis B with the exception of HBsAc in previously vaccinated patients
- Pregnant patients
- HIV infection
- Concurrent chemotherapy or immunotherapy
- Other malignancy within the last 2 years, except for localized cutaneous carcinoma
- Neurological impairment precluding understanding of protocol and the entailed visits and procedures.
- Patients with Renal insufficiency that requires dialysis.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Spain7 sites
Hospital Universitario Reina Sofía
Córdoba, Córdoba, 14004
MD Anderson Internacional España
Madrid, Madrid, 28033
Hospital Universitario La Paz
Madrid, Madrid, 28046
Hospital Clínico de Salamanca
Salamanca, Salamanca, 37007
Hospital Virgen del Rocío
Seville, Sevilla, 41013
Hospital Clínico Universitario de Valencia
Valencia, Valencia, 46010
Hospital Universitario Miguel Servet
Zaragoza, Zaragoza, 50009
About this study
Official title: Phase I Study of the Activity and Safety of Lenalidomide and Rituximab as Non-chemotherapy Therapy for Patients With Recurrent and Refractory Chronic Lymphocytic Leukemia
The rationale for combining lenalidomide with rituximab derives from preclinical observations suggesting that lenalidomide may enhance the ADCC (antigen-dependent cellular cytotoxicity) triggered by monoclonal antibodies such as rituximab. Lenalidomide augments NK cytotoxicity by increasing CD56dimCD3 subset, in addition to inducing IL-2 in T cells. These results provide the cellular and molecular basis for the use of lenalidomide as an adjuvant in immunotherapeutic strategies of monoclonal antibodies (mAb)-based therapies. The combination lenalidomide-rituximab was tested in lymphoma cell lines but not specifically on CLL cell lines. However the observed synergism was attributed to NK cells expansion, thus lending support to the notion that this synergism may operate in other B-cell lymphoproliferative malignancies.
The objective was to develop a non-cytotoxic and effective treatment for CLL that would fulfill an unmet medical need, as a significant proportion of CLL patients are elderly and frail. These patients experience an excess in chemotherapy induced toxicity, often preventing the completion of the planned treatment.
- Conditions
- Chronic Lymphocytic Leukemia
- Being tested
- Lenalidomida and Rituximab
- Keywords
- Recurrent and refractory chronic lymphocytic leukemia
- 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.
Lenalidomida and RituximabDrug
Also called Lenalidomide: REVLIMID, Rituximab: MABTHERA
Lenalidomide: Oral use. It will be administered from day 1 to 21 of 28 days cycles in a total of 6 cycles.
Rituximab, intravenous use. The dose will be administered at the standard (375 mg/m2 in the first cycle and 500 mg/m2 in successive cycles).
In the first cycle Rituximab will be administered in two divided doses:100mg/m2 total on day 1 and the rest up to 375mg/m2 on day 2.
If lenalidomide treatment starts on day 1, Rituximab will be administered, in this first cycle, on days -2 (100 mg/m2) and -1 (275 mg/m2).
In the second and subsequent cycles, 500 mg/m2 of Rituximab will be administered on day -1.
| Study group | Role | What they receive |
|---|---|---|
| Lenalidomida, Rituximab | Experimental | Phase I: Lenalidomide will be administered from day 1 to 21 of 28 days cycles, escalating doses (from 2,5mg to 25 mg).Rituximab dose will be administered at the standard (375 mg/m2 in the first cycle and 500 mg/m2 in successive cycles). Receives: Drug: Lenalidomida and Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: To determine Starting Recommended Dose for the first cycle and the subsequent cycles (Maximal Tolerated Dose)in relapsed B-cell CLL patients.
6 treatment cycles followed by an evaluation visit (between 60-90 days after last dosing) and quarterly follow up visits, until disease progression. Module I: patients on every cohort will have the same dose during treatment, except if they experiment DLT, in which case dose will be decreased (unless they are on the first dose level).
Measured: 5 months
Secondary outcomes (4)
To determine the toxicity profile of LenRtx.
Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits
Measured: 5 months
To determine the time to treatment failure.
Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits
Measured: 5 months
To determine the molecular response rate.
Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits
Measured: 5 months
To determine the clinical response rate (combined morphological and flow cytometry criteria).
6 treatment cycles followed by an evaluation visit (between 60-90 days after last dosing) and quarterly follow up visits, until disease progression
Measured: 5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2010 (estimated)
- Study startApr 2009
- Primary completionDec 2012
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- MD Anderson International Spain SA
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene Corporation
- Responsible party
- Sponsor
- Investigators
- José F Tomas, MD, Principal investigator, MD Anderson Internacional España
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01185262
- Sponsor's protocol ID
- LLC-LENAR-08
- Other IDs
- LLC-LENAR-08
- Acronym
- LLC-LENAR-08
- Status last verified
- Sep 2013
- First submitted
- 17 Dec 2009
- Last updated
- 30 Sep 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of the Activity and Safety of Lenalidomide and Rituximab as Non-chemotherapy Therapy for Patients With Recurrent and Refractory Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT01185262
- Acronym / sponsor ID
- LLC-LENAR-08 / LLC-LENAR-08
- Conditions
- Chronic Lymphocytic Leukemia
- Keywords
- Recurrent and refractory chronic lymphocytic leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- MD Anderson International Spain SAUniversity, hospital or other
- Collaborators
- Celgene Corporation
- Study start
- Apr 2009
- Primary completion
- Dec 2012 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 19 Aug 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The rationale for combining lenalidomide with rituximab derives from preclinical observations suggesting that lenalidomide may enhance the ADCC (antigen-dependent cellular cytotoxicity) triggered by monoclonal antibodies such as rituximab. Lenalidomide augments NK cytotoxicity by increasing CD56dimCD3 subset, in addition to inducing IL-2 in T cells. These results provide the cellular and molecular basis for the use of lenalidomide as an adjuvant in immunotherapeutic strategies of monoclonal antibodies (mAb)-based therapies. The combination lenalidomide-rituximab was tested in lymphoma cell lines but not specifically on CLL cell lines. However the observed synergism was attributed to NK cells expansion, thus lending support to the notion that this synergism may operate in other B-cell lymphoproliferative malignancies.
The objective was to develop a non-cytotoxic and effective treatment for CLL that would fulfill an unmet medical need, as a significant proportion of CLL patients are elderly and frail. These patients experience an excess in chemotherapy induced toxicity, often preventing the completion of the planned treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lenalidomida, Rituximab | Experimental | Drug: Lenalidomida and RituximabPhase I: Lenalidomide will be administered from day 1 to 21 of 28 days cycles, escalating doses (from 2,5mg to 25 mg).Rituximab dose will be administered at the standard (375 mg/m2 in the first cycle and 500 mg/m2 in successive cycles). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Recurrent and refractory CLL patients that have received at least one previous treatment with purine analogs.
- Adequate liver function and renal function.
- ECOG performance status ≤ 2.
- Signed informed consent
- Male and female patients who are fertile agree to use an effective barrier method of birth control to avoid pregnancy.
Key exclusion criteria (7 listed)
- Positive serological markers for hepatitis B with the exception of HBsAc in previously vaccinated patients
- Pregnant patients
- HIV infection
- Concurrent chemotherapy or immunotherapy
- Other malignancy within the last 2 years, except for localized cutaneous carcinoma
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 |
|---|---|---|
| Lenalidomida and RituximabAlso: Lenalidomide: REVLIMID, Rituximab: MABTHERALenalidomide: Oral use. It will be administered from day 1 to 21 of 28 days cycles in a total of 6 cycles. Rituximab, intravenous use. The dose will be administered at the standard (375 mg/m2 in the first cycle and 500 mg/m2 in successive cycles). In the first cycle Rituximab will be administered in two divided doses:100mg/m2 total on day 1 and the rest up to 375mg/m2 on day 2. If lenalidomide treatment starts on day 1, Rituximab will be administered, in this first cycle, on days -2 (100 mg/m2) and -1 (275 mg/m2). In the second and subsequent cycles, 500 mg/m2 of Rituximab will be administered on day -1. | Drug | Lenalidomida, Rituximab |
Primary outcome
Phase I: To determine Starting Recommended Dose for the first cycle and the subsequent cycles (Maximal Tolerated Dose)in relapsed B-cell CLL patients.
Time frame: 5 months
6 treatment cycles followed by an evaluation visit (between 60-90 days after last dosing) and quarterly follow up visits, until disease progression. Module I: patients on every cohort will have the same dose during treatment, except if they experiment DLT, in which case dose will be decreased (unless they are on the first dose level).
4 secondary outcomes
To determine the toxicity profile of LenRtx.
Time frame: 5 months
To determine the time to treatment failure.
Time frame: 5 months
To determine the molecular response rate.
Time frame: 5 months
To determine the clinical response rate (combined morphological and flow cytometry criteria).
Time frame: 5 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2013.
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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.
José F Tomas, MD principal investigator
MD Anderson Internacional España
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lenalidomida and Rituximab in people with Chronic Lymphocytic Leukemia, run by MD Anderson International Spain SA at 7 sites in Spain.
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 5 inclusion and 7 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 30 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Spain. 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 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.
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?
Phase I: To determine Starting Recommended Dose for the first cycle and the subsequent cycles (Maximal Tolerated Dose)in relapsed B-cell CLL patients. (time frame: 5 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 30 Sep 2013.