Lendexal in Patients With Primary Systemic Amyloidosis (AL) Newly Diagnosed

NCT01194791 | Completed Phase 2 DMC

• 2 other identifiers: LENDEXAL2009-017707-28
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 10

Brief 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).
• Toxicity
• Safety (type, frequency, severity and relationship of adverse events to the study drug).
• Duration of response.
• Time to progression.
• Overall survival

Conditions

Primary Systemic Amyloidosis

Keywords

Amyloidosis; Lenalidomide

Outcome Measures

Primary Outcomes (1)

• Hematologic response rate to the association of Lenalidomide, Cyclophosphamide and Dexamethasone

  6 months

Secondary Outcomes (6)

• Organ response rate

  6 months

• Predictors of response (cardiac biomarkers, serum free light chains)

  5 years

• Safety and tolerability

  5 years

• Duration of response

  10 years

• Time to progression

  5 years

Study Arms (1)

Lenalidomide, Cyclophosphamide and Dexamenthasone

EXPERIMENTAL

Drug: Lenalidomide; Drug: Cyclophosphamide; Drug: Dexamethasone

Interventions

Lenalidomide DRUG

Lenalidomide 15 mg by mouth for 21 days followed by 7 days rest during 6 cycles

Also known as: Lendexal

Lenalidomide, Cyclophosphamide and Dexamenthasone

Cyclophosphamide DRUG

Cyclophosphamide 300 mg/m2, on days 1 and 8 every 4 weeks during 6 cycles

Lenalidomide, Cyclophosphamide and Dexamenthasone

Dexamethasone DRUG

Oral dexamethasone 20 mg/day on days 1-4 and 9-12 given at 4-week intervals during 6 cycles

Lenalidomide, Cyclophosphamide and Dexamenthasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• PETHEMA Foundation: lead

Study Sites (10)

Hospital Universitario de Canarias

Santa Cruz de Tenerife, Canary Islands, Spain

Location

Hospital Germans Trias i Pujol

Badalona, Spain

Location

Hospital Clínic

Barcelona, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital Clínico San Carlos

Madrid, Spain

Location

Hospital Doce de Octubre

Madrid, Spain

Location

Hospital Morales Messeguer

Murcia, Spain

Location

Hospitalm Clínico de Salamanca

Salamanca, Spain

Location

Hospital La Fe

Valencia, Spain

Location

Hospital Lozano Blesa

Zaragoza, Spain

Location

Related Publications (1)

• 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.

  PMID: 25974382 DERIVED

Related Links

• Spanish Haematology Association
• CRO

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis; Amyloidosis

Interventions

Lenalidomide; Cyclophosphamide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Bladé Joan, Dr

  Hospital Clinic of Barcelona

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2010
• First Posted: September 3, 2010
• Study Start: October 1, 2010
• Primary Completion: September 1, 2012
• Study Completion: December 1, 2016
• Last Updated: April 25, 2017

Record last verified: 2015-11

Locations

ES (10)