Lendexal in Patients With Primary Systemic Amyloidosis (AL) Newly Diagnosed (LENDEXAL)
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).
- Safety (type, frequency, severity and relationship of adverse events to the study drug).
- Duration of response.
- Time to progression.
- Overall survival
Primary Systemic Amyloidosis
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- Hematologic response rate to the association of Lenalidomide, Cyclophosphamide and Dexamethasone [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Organ response rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Predictors of response (cardiac biomarkers, serum free light chains) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- Safety and tolerability [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
- Duration of response [ Time Frame: 10 years ] [ Designated as safety issue: No ]
- Time to progression [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: 10 yeras ] [ Designated as safety issue: No ]
|Study Start Date:||October 2010|
|Estimated Study Completion Date:||December 2016|
|Primary Completion Date:||September 2012 (Final data collection date for primary outcome measure)|
|Experimental: Lenalidomide, Cyclophosphamide and Dexamenthasone||
Lenalidomide 15 mg by mouth for 21 days followed by 7 days rest during 6 cycles
Other Name: LendexalDrug: Cyclophosphamide
Cyclophosphamide 300 mg/m2, on days 1 and 8 every 4 weeks during 6 cyclesDrug: Dexamethasone
Oral dexamethasone 20 mg/day on days 1-4 and 9-12 given at 4-week intervals during 6 cycles
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01194791
|Hospital Universitario de Canarias|
|Tenerife, Islas Canarias, Spain|
|Hospital Germans Trias i Pujol|
|Hospital de la Santa Creu i Sant Pau|
|Hospital Doce de Octubre|
|Hospital Clínico San Carlos|
|Hospital Morales Messeguer|
|Hospitalm Clínico de Salamanca|
|Hospital La Fe|
|Hospital Lozano Blesa|
|Study Chair:||Bladé Joan, Dr||Hospital Clinic of Barcelona|