Chronic Lymphatic LeukemiaPhase 1/2LENDEX-LLC-09NCT01246557
Study Assessing Safety and Efficiency of the Lenalidomide and Dexamethasone Combination in Patients With Chronic Lymphatic Leukemia (CLL) Relapsing or Resistant to Treatment
A Phase 1/2 study testing Lenalidomide and Dexamethasone in people with Chronic Lymphatic Leukemia, run by Hospital Universitari Vall d'Hebron Research Institute at 6 sites in Spain.
Trial summary
Despite certain notable progress, treatment of patients with Chronic Lymphatic Leukemia (CLL) is still disappointing. Although thanks to the use of treatment of (immune) chemotherapy, mainly based on fludarabine, rituximab and alemtuzumab, the rate of complete response (CR) has increased from minus 10% observed when… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphatic Leukemia
- What is being tested?
- Lenalidomide and Dexamethasone
- Type of treatment
- Pill or oral medicine
- How many people
- 20 participants
- Where
- 6 sitesSpain
- Study dates
- Dec 2009to Apr 2014
- 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
- The patients will have to meet the following inclusion criteria in order to be included in the study:
- To understand and voluntarily sign an informed consent form.
- To be ≥ 18 years old upon the signature of the informed consent form.
- To be able to fulfill the visits program of the study and other protocol requirements.
- To have a CLL documented diagnose (NCI/WG criteria) relapsing or resistant to at least one prior treatment and not to meet the requirements for an intensive rescue therapy. Prior treatment(s) will have to include fludarabine.
- All prior anti-cancer therapies, including radiation, hormonal therapy and surgery, will have to be interrupted at leas 4 weeks before the treatment in this study.
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- Functional state 0-2 (ECOG).
- Women with childbearing potential (FCBP) will have to:
- understand the teratogenic risk of the study drug. accept the simultaneous use of two reliable contraception methods or to practice the abstinence of heterosexual relations during the following periods of time related to this study: 1) during at least 4 weeks before starting the drug of the study; 2) while participating in the study; y 3) during at least 4 weeks following the interruption of the study. The two reliable contraceptive methods will have to include one highly effective (this is, intrauterine device (IUD), hormonal (pills injections or implants), tubal ligation, vasectomy of the partner) and an barrier effective additional method (this is, latex preservative, diaphragm, cervical cap). Women with a childbearing potential will have to visit a specialist in contraceptive methods if necessary.
- Before starting the drug under study: • Women with childbearing potential will have to undergo two negative pregnancy tests (sensibility of at least 25 mUI/ml) before starting the drug under study. The first test will take place at the visit date or within a period of 3 days before starting the drug under study and the second.The patient will not receive the drug until the investigator has verified that the results of the tests are negative.
- Men:
- They will have to accept the use of latex preservatives during sexual relations with women with childbearing potential while they participate in the study and during at least one week following the interruption of the study, if it is women with childbearing potential (FCBP) and no use contraception.
- They will have to accept to refrain from donating blood or semen during their participation in the study and during at least 28 days following the interruption of the study.
- In the event of pregnancy or positive pregnancy test in a participant in the study, or the partner of a male participant in the study, during his participation, the drug under study will be immediately interrupted.
- Capable of receiving Acetyl Salicylic Acid (100 or 300 mg) on a daily basis as prophylactic anticoagulation. (Patients who do not tolerate ASA may use acenocumarol or low molecular weight heparin).
Who cannot join
- Patients will not have to fulfill any of the following exclusion criteria to be included in the study.
- Any serious medical disorder, laboratory abnormality or psychiatric disease hindering the signature of the informed consent by the patient.
- Pregnant women or in lactation period.
- Any disorder, including the presence of laboratory abnormalities, which puts the patient at unacceptable risk if he/she participates in the study or hindered the capacity to understand the information of the study.
- Use of any other experimental drug or therapy in the period of 28 days from the base visit.
- Known hyper-sensibility to thalidomide.
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- Development of erythema nodosum if it is characterized by a descamative eruption while taken thalidomide or similar drugs.
- Any prior use of lenalidomide.
- A concurrent use of other agents or anticancer treatments.
- HIV-positive or infectious hepatitis type A, B or C.
- Candidates eligible for intensive rescue therapies (ex. R-CHOP plus alemtuzumab, allogenic transplant)
- Richter transformation (active) or CNS participation (active)
- Any of the following laboratory abnormalities:
- Neutrophil absolute count < 0.5 x 109/L Platelet count < 25 x 109/L Calculated Creatinine Clearance <50 mL/min Total serum bilirubin > higher normal limit (HNL) AST and ALT >3 x higher normal limit (HNL) Autoimmune non controlled hemolytic anemia or thrombocytopenia.
- History of another neoplastic disease during ≥ 5 years unless base cells or epidermoid carcinoma in situ of cervix or breast recently treated.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Spain6 sites
Centro Médico Teknon
Barcelona, Barcelona, 08022
Hospital de la Santa Creu i Sant Pau
Barcelona, Barcelona, 08025
Hospital Universitari Valle Hebron
Barcelona, Barcelona, 08035
Hospital Clinico Universitario de Barcelona
Barcelona, Barcelona, 08036
Hospital Joan XXIII
Tarragona, Tarragona, 43007
Hospital Clínico Universitario de Valencia
Valencia, Valencia, 46010
About this study
Official title: Open Label Multi-center Pilot Phase I/II Non-controlled Clinical Trial to Assess Safety and Efficieecy of the Lenalidomide and Dexamethasone Association in Patients With Chronic Relapse or Treatment Resistant Lymphatic Leukemia Following Treatment Containing Fludarabine.
Despite certain notable progress, treatment of patients with Chronic Lymphatic Leukemia (CLL) is still disappointing. Although thanks to the use of treatment of (immune) chemotherapy, mainly based on fludarabine, rituximab and alemtuzumab, the rate of complete response (CR) has increased from minus 10% observed when clorambucil was the core of the therapy to a 60-70%, with time all patients relapse and most of them die at the end due to the disease or to involvements related to the treatment. Progress when understanding the CLL biology have cleared a series of aspects: 1) there is a significant proportion of CLL cells actively copying themselves, contrary to the opinion that most of CLL cells are in G0 phase of the cell cycle; 2) Immune regulatory mechanism basically measured by T cells and NK cells have an important role in the continuous accumulation of CLL cells in the body; 3) Cells of the stroma are essential to maintain survival of CLL cells through a series of cytokines or chemokines. Under the light of this evidence, it is worth studying new treatment modes directed not only to CLL cells but also to the microenvironment and immune functions.
Lenalidomide is being investigated as treatment for several oncologic indications including myelodysplastic syndromes, multiple myeloma and non-Hodgkin lymphoma. Within the scope of CLL, it has been proved that lenalidomide is active in patients with relapsing / treatment resistant CLL patients. Forty five patients with relapsing CLL, 51% resistant to fludarabine, where included in a phase II study and were treated orally with 25 mg of lenalidomide on days 1 to 21 of a cycle of 28 days. The total response rate was of 47% with up to a 9% of complete responses.
Read more
The combination of lenalidomide with dexamethasone is being investigated in multiple myeloma and has revealed as a highly efficient treatment in relapsing/ treatment resistant patients as well as in those newly diagnosed. Bearing in mind that both drugs, lenalidomide and dexamethasone, are clinically active in CLL the investigators have designed a study with this combination in relapsing or treatment resistant patients following treatments containing fludarabine which do not meet the requirements for an intensive rescue treatment.
Given initial doses of 10 and 25 mg of lenalidomide daily may be associated with tumor lysis cases, it is proposed a low initial dose of lenalidomide in the first cycle 2.5mg., with further increases to prevent the occurrence of tumor lysis syndrome
- Conditions
- Chronic Lymphatic Leukemia
- Being tested
- Lenalidomide, Dexamethasone
- Keywords
- Patients with Chronic Lymphatic Leukemia relapsing or resistant to treatment
- 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 - Revlimid®: an analogue of thalidomide, is an immunomodulator agent with anti-angiogenic properties. The chemical name is 3-(4 ́-aminoisoindoline-1 ́ona)-1- piperidine-2,6-dione.
REVLIMID® (lenalidomide) is available in capsules of 5 mg, 10 mg and 15 mg p.o.. Each capsule contains lenalidomide as active ingredient and the following non active ingredients: anhydrous lactose, microcrystalline cellulose, sodium croscarmellose and magnesium stearate.
DexamethasoneDrug
Also called Commercial drug according to standard clinical practices of the center.
Dexamethasone will be administered as 20 mg/day (on days 1 to 4) for oral administration.
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the safety of the association of lenalidomide and dexamethasone in patients with relapsed or refractory CLL
The first step will be an interim analysis of toxicity to determine the safety of the first lenalidomide cohort dosage (2.5 mg/day). This analysis will be performed after six subjects complete 3 months of treatment. A second analysis of toxicity will be performed after the second lenalidomide dosage cohort (six patients with 5mg/day) complete 3 months of treatment.
Measured: At the finalization of the second cycle of the treatment of the last patient (average 5 months of last patient inclusion date)
Secondary outcomes (5)
To assess the efficacy of lenalidomide and dexamethasone in patients with Chronic Lymphocytic Leukemia (CLL) relapsing of resistant to treatment.
Efficacy endpoint: Duration of response.
Measured: Average of 20 months from the last patient inclusion.
To assess the efficacy of lenalidomide and dexamethasone in patients with Chronic Lymphocytic Leukemia (CLL) relapsing of resistant to treatment.
Efficacy endpoint: Time to response.
Measured: Average of 9 months from the last patient inclusion.
To assess the efficacy of lenalidomide and dexamethasone in patients with Chronic Lymphocytic Leukemia (CLL) relapsing of resistant to treatment.
Efficacy endpoint: Progresion-free survival.
Measured: Average of 20 months from the last patient inclusion.
To assess the efficacy of lenalidomide and dexamethasone in patients with Chronic Lymphocytic Leukemia (CLL) relapsing of resistant to treatment.
Efficacy endpoint: Treatment response.
Measured: Average of 20 months from the last patient inclusion.
To assess the efficacy of lenalidomide and dexamethasone in patients with Chronic Lymphocytic Leukemia (CLL) relapsing of resistant to treatment.
Efficacy endpoint: Overall survival.
Measured: Average of 20 months from the last patient inclusion.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2010 (estimated)
- Study startDec 2009
- Primary completionApr 2014
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Lymphatic LeukemiaStudies of the same condition, open and under way.
- More trials run by Hospital Universitari Vall d'Hebron Research InstituteThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01246557
- Sponsor's protocol ID
- LENDEX-LLC-09
- Other IDs
- 2009-012571-95, 2009
- Acronym
- LENDEX-LLC-09
- Status last verified
- Feb 2011
- First submitted
- 30 Sep 2010
- Last updated
- 4 Apr 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label Multi-center Pilot Phase I/II Non-controlled Clinical Trial to Assess Safety and Efficieecy of the Lenalidomide and Dexamethasone Association in Patients With Chronic Relapse or Treatment Resistant Lymphatic Leukemia Following Treatment Containing Fludarabine.
- ClinicalTrials.gov ID
- NCT01246557
- Acronym / sponsor ID
- LENDEX-LLC-09 / LENDEX-LLC-09
- Conditions
- Chronic Lymphatic Leukemia
- Keywords
- Patients with Chronic Lymphatic Leukemia relapsing or resistant to treatment
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Hospital Universitari Vall d'Hebron Research InstituteUniversity, hospital or other
- Study start
- Dec 2009
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 23 Nov 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.
Despite certain notable progress, treatment of patients with Chronic Lymphatic Leukemia (CLL) is still disappointing. Although thanks to the use of treatment of (immune) chemotherapy, mainly based on fludarabine, rituximab and alemtuzumab, the rate of complete response (CR) has increased from minus 10% observed when clorambucil was the core of the therapy to a 60-70%, with time all patients relapse and most of them die at the end due to the disease or to involvements related to the treatment. Progress when understanding the CLL biology have cleared a series of aspects: 1) there is a significant proportion of CLL cells actively copying themselves, contrary to the opinion that most of CLL cells are in G0 phase of the cell cycle; 2) Immune regulatory mechanism basically measured by T cells and NK cells have an important role in the continuous accumulation of CLL cells in the body; 3) Cells of the stroma are essential to maintain survival of CLL cells through a series of cytokines or chemokines. Under the light of this evidence, it is worth studying new treatment modes directed not only to CLL cells but also to the microenvironment and immune functions.
Lenalidomide is being investigated as treatment for several oncologic indications including myelodysplastic syndromes, multiple myeloma and non-Hodgkin lymphoma. Within the scope of CLL, it has been proved that lenalidomide is active in patients with relapsing / treatment resistant CLL patients. Forty five patients with relapsing CLL, 51% resistant to fludarabine, where included in a phase II study and were treated orally with 25 mg of lenalidomide on days 1 to 21 of a cycle of 28 days. The total response rate was of 47% with up to a 9% of complete responses.
The combination of lenalidomide with dexamethasone is being investigated in multiple myeloma and has revealed as a highly efficient treatment in relapsing/ treatment resistant patients as well as in those newly diagnosed. Bearing in mind that both drugs, lenalidomide and dexamethasone, are clinically active in CLL the investigators have designed a study with this combination in relapsing or treatment resistant patients following treatments containing fludarabine which do not meet the requirements for an intensive rescue treatment.
Given initial doses of 10 and 25 mg of lenalidomide daily may be associated with tumor lysis cases, it is proposed a low initial dose of lenalidomide in the first cycle 2.5mg., with further increases to prevent the occurrence of tumor lysis syndrome
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- The patients will have to meet the following inclusion criteria in order to be included in the study:
- To understand and voluntarily sign an informed consent form.
- To be ≥ 18 years old upon the signature of the informed consent form.
- To be able to fulfill the visits program of the study and other protocol requirements.
- To have a CLL documented diagnose (NCI/WG criteria) relapsing or resistant to at least one prior treatment and not to meet the requirements for an intensive rescue therapy. Prior treatment(s) will have to include fludarabine.
Key exclusion criteria (15 listed)
- Patients will not have to fulfill any of the following exclusion criteria to be included in the study.
- Any serious medical disorder, laboratory abnormality or psychiatric disease hindering the signature of the informed consent by the patient.
- Pregnant women or in lactation period.
- Any disorder, including the presence of laboratory abnormalities, which puts the patient at unacceptable risk if he/she participates in the study or hindered the capacity to understand the information of the study.
- Use of any other experimental drug or therapy in the period of 28 days from the base visit.
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 |
|---|---|---|
| LenalidomideAlso: REVLIMID®Lenalidomide - Revlimid®: an analogue of thalidomide, is an immunomodulator agent with anti-angiogenic properties. The chemical name is 3-(4 ́-aminoisoindoline-1 ́ona)-1- piperidine-2,6-dione. REVLIMID® (lenalidomide) is available in capsules of 5 mg, 10 mg and 15 mg p.o.. Each capsule contains lenalidomide as active ingredient and the following non active ingredients: anhydrous lactose, microcrystalline cellulose, sodium croscarmellose and magnesium stearate. | Drug | – |
| DexamethasoneAlso: Commercial drug according to standard clinical practices of the center.Dexamethasone will be administered as 20 mg/day (on days 1 to 4) for oral administration. | Drug | – |
Primary outcome
To assess the safety of the association of lenalidomide and dexamethasone in patients with relapsed or refractory CLL
Time frame: At the finalization of the second cycle of the treatment of the last patient (average 5 months of last patient inclusion date)
The first step will be an interim analysis of toxicity to determine the safety of the first lenalidomide cohort dosage (2.5 mg/day). This analysis will be performed after six subjects complete 3 months of treatment. A second analysis of toxicity will be performed after the second lenalidomide dosage cohort (six patients with 5mg/day) complete 3 months of treatment.
5 secondary outcomes
To assess the efficacy of lenalidomide and dexamethasone in patients with Chronic Lymphocytic Leukemia (CLL) relapsing of resistant to treatment.
Time frame: Average of 20 months from the last patient inclusion.
To assess the efficacy of lenalidomide and dexamethasone in patients with Chronic Lymphocytic Leukemia (CLL) relapsing of resistant to treatment.
Time frame: Average of 9 months from the last patient inclusion.
To assess the efficacy of lenalidomide and dexamethasone in patients with Chronic Lymphocytic Leukemia (CLL) relapsing of resistant to treatment.
Time frame: Average of 20 months from the last patient inclusion.
To assess the efficacy of lenalidomide and dexamethasone in patients with Chronic Lymphocytic Leukemia (CLL) relapsing of resistant to treatment.
Time frame: Average of 20 months from the last patient inclusion.
To assess the efficacy of lenalidomide and dexamethasone in patients with Chronic Lymphocytic Leukemia (CLL) relapsing of resistant to treatment.
Time frame: Average of 20 months from the last patient inclusion.
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 4 Apr 2014.
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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.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Lenalidomide and Dexamethasone in people with Chronic Lymphatic Leukemia, run by Hospital Universitari Vall d'Hebron Research Institute at 6 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 15 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 4 Apr 2014. 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 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 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?
To assess the safety of the association of lenalidomide and dexamethasone in patients with relapsed or refractory CLL (time frame: At the finalization of the second cycle of the treatment of the last patient (average 5 months of last patient inclusion date)). 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 4 Apr 2014.