Primary Systemic AmyloidosisPhase 2LENDEXALNCT01194791
Lendexal in Patients With Primary Systemic Amyloidosis (AL) Newly Diagnosed
A Phase 2 study testing Lenalidomide, Cyclophosphamide and Dexamethasone in people with Primary Systemic Amyloidosis, run by PETHEMA Foundation at 10 sites in Spain.
Trial summary
Primary outcome measure: Hematologic response rate to the association of Lenalidomide, Cyclophosphamide and Dexamethasone. Secondary outcome measures: Organ response rate. Predictors of response (cardiac biomarkers, serum free light chains). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Systemic Amyloidosis
- What is being tested?
- Lenalidomide, Cyclophosphamide and Dexamethasone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 10 sitesSpain
- Study dates
- Oct 2010to Dec 2016
- Phase
- Phase 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
- 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 according with investigator criteria.
- Diagnosis of symptomatic primary systemic amyloidosis based on tissue Congo red positive staining as well as positive immunohistochemical staining for light chains or presence of a monoclonal protein in serum and/or urine or clonal bone marrow plasma cells
- Previously untreated disease
- Patients should not candidates for up-front high-dose therapy/stem cell transplantation
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- Serologically measurable disease defined as follows:
- Evidence of a monoclonal light chain in serum and urine by immunofixation Raise of the level of circulating free light chains above the ordinary limits and an abnormal relationship kappa/lambda.
- Performance status ECOG ≤ 2 (see Annex 3).
- Laboratory tests results within these ranges:
- Absolute neutrophil count ≥ 1 x 10 9/ L. Platelet count ≥ 100 x 10 9/ L Serum creatinine less than 3.0 mg/dL Serum bilirubin less than 3.0 mg/dL
- Females of childbearing potential (FCBP) must agree to: Know the teratogenic risks of the study drug
- Commit to use contraceptives during the 4 weeks before the start of this study drug treatment, during the treatment and also 4 weeks after it, even amenorrheic cases. All of it applies always except women committed to maintain sexual abstinence confirming it monthly. Some of effective contraceptives are:
- Birth control implant Levonorgestrel-releasing intrauterine device. Depot medroxyprogesterone acetate Tubal ligation Sexual intercourse only with a vasectomized partner. The effectiveness of vasectomy must be confirmed by two semen analysis; the result must be negative Inhibiting ovulation pill progesterone only (for example: desogestrel) if it is determined that the patient doesn't use an effective contraceptive method will be referred to a skilled health professional to receive advice on contraception, so that they can begin to birth control measures.
- It's discouraged combine oral contraceptives in myeloma multiple women cases treated with Lenalidomide combined with Dexamethasone due to high venous thromboembolism risk. In case these kind of patient were having combined oral contraceptives, she must change to another one of list above. Risks of venous thromboembolism will remain during the 3 or 4 weeks after discontinue combine oral contraceptives treatment. Concomitant treatment with dexamethasone reduces the effectiveness of contraceptive steroids.
- Implants and levonorgestrel-releasing intrauterine systems are related to higher risks of infections at the moment of the implant or when there is metrorrhagia. It should be considered prophylactic treatment with antibiotics for neutropenic patients.
- Normally it's discouraged copper intrauterine devices because of the infection risk and menstrual blood loss at the moment of the implant for patients with neutropenia or thrombocytopenia.
- Women patients must follow all warnings for an effective contraception, even if she is amenorrheic.
- Women patients must be aware about effects of pregnancy and go to a health care centre urgently in case of pregnancy risk.
- She must take a pregnancy test with a minimum sensitivity of 25 mUl/ml, under medical supervision, when the study visits or three days before the visit, when she were 4 weeks at least using effective contraceptive methods. This requirement applies for women who practice a complete and continuous sexual abstinence. Test should confirm that the patient is not pregnant at the time of starting treatment.
- She must take a pregnancy test, under medical supervision, each 4 weeks, even a pregnancy test 4 weeks after the end of the study treatment, except in case of a confirmed tubal ligation. Pregnancy test should be performed the day of the study's visit or during the three days before it. This requirement also applies for childbearing women who practice a complete and continuous sexual abstinence.
- Male patients must: Undertake to use latex condoms during treatment with study medication including all periods of interruption of doses, even one week after finishing treatment if his partner is a woman of childbearing who doesn't use contraceptive methods.
- Commit not to donate semen during treatment with study medication and even one week after finishing treatment.
- All patients should: Refrain from donating blood during treatment with study medication and even one week after finishing treatment.
- Refrain from sharing the study medication with other people and return unused study medication to the investigator or the pharmacist.
Who cannot join
- Localized cutaneous AL, only carpal tunnel syndrome, merely vascular amyloid in the bone marrow biopsy, AL in a plasmacytoma or AL associated to multiple myeloma (>30% plasma cells in bone marrow, lytic bone lesions, hypercalcemia, plasmacytomas).
- Other causes of amyloidosis (secondary, familial, senile).
- Candidates for high dose chemotherapy/ stem cell transplant.
- Previously treated AL.
- Any condition including laboratory abnormalities, which placed the subjects at unacceptable risk if he/she were to participating the study or confounds the ability to interpret data from the study.
- Use of any other experimental drug or therapy within 28 days prior to baseline.
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- Any prior use of lenalidomide
- Any cancer in the previous 5 years, except no melanoma skin cancer, cervix or prostate cancer treated in the initial state with prostate-specific antigen within normal limits.
- Known positive for HIV.
- Cardiac ejection fraction below 50%
- Pregnant or breast-feeding (can not breast-feed while taking lenalidomide)
- Patients who are not able to use antithrombotic prophylaxis or reject.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Spain10 sites
Hospital Germans Trias i Pujol
Badalona
Hospital Clínic
Barcelona
Hospital de la Santa Creu i Sant Pau
Barcelona
Hospital Clínico San Carlos
Madrid
Hospital Doce de Octubre
Madrid
Hospital Morales Messeguer
Murcia
Hospitalm Clínico de Salamanca
Salamanca
Hospital Universitario de Canarias
Santa Cruz de Tenerife, Canary Islands
Hospital La Fe
Valencia
Hospital Lozano Blesa
Zaragoza
About this study
Official title: A Multicentric, Phase II Trial of Lenalidomide, Cyclophosphamide and Dexamethasone in Patients With Primary Systemic Amyloidosis (AL) Newly Diagnosed, Not Candidates for Hematopoietic Stem Cell Transplantation
Primary outcome measure:
- Hematologic response rate to the association of Lenalidomide, Cyclophosphamide and Dexamethasone.
Secondary outcome measures:
- Organ response rate.
- Predictors of response (cardiac biomarkers, serum free light chains).
- Toxicity
- Safety (type, frequency, severity and relationship of adverse events to the study drug).
- Duration of response.
- Time to progression.
- Overall survival
Read the detailed description
It is a multicenter, single arm treatment, phase II study of the combination in one treatment arm with Lenalidomide, Cyclophosphamide and Dexamethasone.
Subjects who qualify for participation will receive lenalidomide plus dexamethasone and cyclophosphamide in 4-week cycles. Subjects will be seen (study visits) every 2 weeks for the first 3 cycles of therapy and monthly thereafter.
Cycles of lenalidomide/dexamethasone/cyclophosphamide will consists of lenalidomide 15 mg by mouth for 21 days followed by 7 days rest and 300 mg/m2 of cyclophosphamide on days 1 and 8 plus oral dexamethasone 20 mg/day on days 1-4 and 9-12 given at 4-week intervals. Patients will be treated with 6 cycles of therapy with the option to continue beyond as long there is evidence of response. In this case the dose of lenalidomide will be the same and the dose of the dexamethasone will be administered only on days 1 to 4 of each cycle and the dose of cyclophosphamide only day 1 during 6 cycles. After 12 cycles if the patients remaining in response, will be treated with 10 mg/day, cyclophosphamide day 1, and dexamethasone will be administered on days 1 to 4 of each cycle.
For the first 3 cycles, patients will be followed for adverse events with hematologic control every 2 weeks and monthly thereafter. Patients will be required to have a blood work-up including total serum protein and serum protein electrophoresis, urine protein studies and a clinical visit before each cycle. Organ involvement will be assessed every 4 cycles during the first year of therapy. Hematologic response will be assessed every 3 months and organ response every 6 months after the first year of treatment.
Treatment modifications will be based on adverse events graded according to the Common Terminology Criteria for Adverse Events (CTCAE Version 3.0).
There will be 30 patients enrolled.
The trial consists of three periods: pre-treatment, treatment and follow up period.
Pre-treatment phase: include the enrolment visit in order to determine if the patient is eligible to participate in the study. The patient will sign the Informed Consent Form to take part in the study, and will receive detailed information about the treatment, its benefits and risks.
Treatment phase: include the 12 cycles of 28 days treatment with Lenalidomide, Cyclophosphamide and Dexamethasone as induction therapy followed with low doses of Lenalidomide and Dexamethasone during three years until progression or unacceptable toxicity levels.
Follow up phase: Once the clinical trial has finished, patients will be followed during usual clinical practice visits where progression, free survival and overall survival will be evaluated.
- Conditions
- Primary Systemic Amyloidosis
- Being tested
- Lenalidomide, Cyclophosphamide, Dexamethasone
- Keywords
- Amyloidosis, Lenalidomide
- Medical subject headings
- Immunoglobulin Light-chain Amyloidosis, Amyloidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenalidomideDrug
Also called Lendexal
Lenalidomide 15 mg by mouth for 21 days followed by 7 days rest during 6 cycles
CyclophosphamideDrug
Cyclophosphamide 300 mg/m2, on days 1 and 8 every 4 weeks during 6 cycles
DexamethasoneDrug
Oral dexamethasone 20 mg/day on days 1-4 and 9-12 given at 4-week intervals during 6 cycles
| Study group | Role | What they receive |
|---|---|---|
| Lenalidomide, Cyclophosphamide and Dexamenthasone | Experimental | Not described Receives: Drug: Lenalidomide; Drug: Cyclophosphamide; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hematologic response rate to the association of Lenalidomide, Cyclophosphamide and Dexamethasone
Measured: 6 months
Secondary outcomes (6)
Organ response rate
Measured: 6 months
Predictors of response (cardiac biomarkers, serum free light chains)
Measured: 5 years
Safety and tolerability
Measured: 5 years
Duration of response
Measured: 10 years
Time to progression
Measured: 5 years
Overall survival
Measured: 10 yeras
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2010 (estimated)
- Study startOct 2010
- Primary completionSep 2012
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary Systemic AmyloidosisStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- PETHEMA Foundation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Bladé Joan, Dr, Study chair, Hospital Clinic of Barcelona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01194791
- Sponsor's protocol ID
- LENDEXAL
- Other IDs
- 2009-017707-28, 2009
- Acronym
- LENDEXAL
- Status last verified
- Nov 2015
- First submitted
- 26 Jul 2010
- Last updated
- 25 Apr 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Cibeira MT, Oriol A, Lahuerta JJ, Mateos MV, de la Rubia J, Hernandez MT, Granell M, Fernandez de Larrea C, San Miguel JF, Blade J; PETHEMA cooperative study group. A phase II trial of lenalidomide, dexamethasone and cyclophosphamide for newly diagnosed patients with systemic immunoglobulin light chain amyloidosis. Br J Haematol. 2015 Sep;170(6):804-13. doi: 10.1111/bjh.13500. Epub 2015 May 14.
PubMed 25974382
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentric, Phase II Trial of Lenalidomide, Cyclophosphamide and Dexamethasone in Patients With Primary Systemic Amyloidosis (AL) Newly Diagnosed, Not Candidates for Hematopoietic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT01194791
- Acronym / sponsor ID
- LENDEXAL / LENDEXAL
- Conditions
- Primary Systemic Amyloidosis
- Keywords
- Amyloidosis, Lenalidomide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- PETHEMA FoundationUniversity, hospital or other
- Study start
- Oct 2010
- Primary completion
- Sep 2012 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 3 Sep 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.
Primary outcome measure:
- Hematologic response rate to the association of Lenalidomide, Cyclophosphamide and Dexamethasone.
Secondary outcome measures:
- Organ response rate.
- Predictors of response (cardiac biomarkers, serum free light chains).
- Toxicity
- Safety (type, frequency, severity and relationship of adverse events to the study drug).
- Duration of response.
- Time to progression.
- Overall survival
Detailed description
It is a multicenter, single arm treatment, phase II study of the combination in one treatment arm with Lenalidomide, Cyclophosphamide and Dexamethasone.
Subjects who qualify for participation will receive lenalidomide plus dexamethasone and cyclophosphamide in 4-week cycles. Subjects will be seen (study visits) every 2 weeks for the first 3 cycles of therapy and monthly thereafter.
Cycles of lenalidomide/dexamethasone/cyclophosphamide will consists of lenalidomide 15 mg by mouth for 21 days followed by 7 days rest and 300 mg/m2 of cyclophosphamide on days 1 and 8 plus oral dexamethasone 20 mg/day on days 1-4 and 9-12 given at 4-week intervals. Patients will be treated with 6 cycles of therapy with the option to continue beyond as long there is evidence of response. In this case the dose of lenalidomide will be the same and the dose of the dexamethasone will be administered only on days 1 to 4 of each cycle and the dose of cyclophosphamide only day 1 during 6 cycles. After 12 cycles if the patients remaining in response, will be treated with 10 mg/day, cyclophosphamide day 1, and dexamethasone will be administered on days 1 to 4 of each cycle.
For the first 3 cycles, patients will be followed for adverse events with hematologic control every 2 weeks and monthly thereafter. Patients will be required to have a blood work-up including total serum protein and serum protein electrophoresis, urine protein studies and a clinical visit before each cycle. Organ involvement will be assessed every 4 cycles during the first year of therapy. Hematologic response will be assessed every 3 months and organ response every 6 months after the first year of treatment.
Treatment modifications will be based on adverse events graded according to the Common Terminology Criteria for Adverse Events (CTCAE Version 3.0).
There will be 30 patients enrolled.
The trial consists of three periods: pre-treatment, treatment and follow up period.
Pre-treatment phase: include the enrolment visit in order to determine if the patient is eligible to participate in the study. The patient will sign the Informed Consent Form to take part in the study, and will receive detailed information about the treatment, its benefits and risks.
Treatment phase: include the 12 cycles of 28 days treatment with Lenalidomide, Cyclophosphamide and Dexamethasone as induction therapy followed with low doses of Lenalidomide and Dexamethasone during three years until progression or unacceptable toxicity levels.
Follow up phase: Once the clinical trial has finished, patients will be followed during usual clinical practice visits where progression, free survival and overall survival will be evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lenalidomide, Cyclophosphamide and Dexamenthasone | Experimental | Drug: Lenalidomide, Drug: Cyclophosphamide, Drug: Dexamethasone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- 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 according with investigator criteria.
- Diagnosis of symptomatic primary systemic amyloidosis based on tissue Congo red positive staining as well as positive immunohistochemical staining for light chains or presence of a monoclonal protein in serum and/or urine or clonal bone marrow plasma cells
- Previously untreated disease
Key exclusion criteria (12 listed)
- Localized cutaneous AL, only carpal tunnel syndrome, merely vascular amyloid in the bone marrow biopsy, AL in a plasmacytoma or AL associated to multiple myeloma (>30% plasma cells in bone marrow, lytic bone lesions, hypercalcemia, plasmacytomas).
- Other causes of amyloidosis (secondary, familial, senile).
- Candidates for high dose chemotherapy/ stem cell transplant.
- Previously treated AL.
- Any condition including laboratory abnormalities, which placed the subjects at unacceptable risk if he/she were to participating the study or confounds the ability to interpret data from the study.
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: LendexalLenalidomide 15 mg by mouth for 21 days followed by 7 days rest during 6 cycles | Drug | Lenalidomide, Cyclophosphamide and Dexamenthasone |
| CyclophosphamideCyclophosphamide 300 mg/m2, on days 1 and 8 every 4 weeks during 6 cycles | Drug | Lenalidomide, Cyclophosphamide and Dexamenthasone |
| DexamethasoneOral dexamethasone 20 mg/day on days 1-4 and 9-12 given at 4-week intervals during 6 cycles | Drug | Lenalidomide, Cyclophosphamide and Dexamenthasone |
Primary outcome
Hematologic response rate to the association of Lenalidomide, Cyclophosphamide and Dexamethasone
Time frame: 6 months
6 secondary outcomes
Organ response rate
Time frame: 6 months
Predictors of response (cardiac biomarkers, serum free light chains)
Time frame: 5 years
Safety and tolerability
Time frame: 5 years
Duration of response
Time frame: 10 years
Time to progression
Time frame: 5 years
Overall survival
Time frame: 10 yeras
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 25 Apr 2017.
- Derived from this study: PubMed 25974382Cibeira MT, Oriol A, Lahuerta JJ, Mateos MV, de la Rubia J, Hernandez MT, Granell M, Fernandez de Larrea C, San Miguel JF, Blade J; PETHEMA cooperative study group. A phase II trial of lenalidomide, dexamethasone and cyclophosphamide for newly diagnosed patients with systemic immunoglobulin light chain amyloidosis. Br J Haematol. 2015 Sep;170(6):804-13. doi: 10.1111/bjh.13500. Epub 2015 May 14.
- Spanish Haematology AssociationLink provided by the sponsor.
- CROLink 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.
Bladé Joan, Dr study chair
Hospital Clinic of Barcelona
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lenalidomide, Cyclophosphamide and Dexamethasone in people with Primary Systemic Amyloidosis, run by PETHEMA Foundation at 10 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 25 inclusion and 12 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 25 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 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 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?
Hematologic response rate to the association of Lenalidomide, Cyclophosphamide and Dexamethasone (time frame: 6 months). 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 NCT01194791, which also lists 1 linked publication.
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 25 Apr 2017.