search
Back to results

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

Primary Purpose

Primary Systemic Amyloidosis

Status
Completed
Phase
Phase 2
Locations
Spain
Study Type
Interventional
Intervention
Lenalidomide
Cyclophosphamide
Dexamethasone
Sponsored by
PETHEMA Foundation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Systemic Amyloidosis focused on measuring Amyloidosis, Lenalidomide

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.

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.

Exclusion Criteria:

  • 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.

Sites / Locations

  • Hospital Universitario de Canarias
  • Hospital Germans Trias i Pujol
  • Hospital Clínic
  • Hospital de la Santa Creu i Sant Pau
  • Hospital Clínico San Carlos
  • Hospital Doce de Octubre
  • Hospital Morales Messeguer
  • Hospitalm Clínico de Salamanca
  • Hospital La Fe
  • Hospital Lozano Blesa

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lenalidomide, Cyclophosphamide and Dexamenthasone

Arm Description

Outcomes

Primary Outcome Measures

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 and tolerability
Duration of response
Time to progression
Overall survival

Full Information

First Posted
July 26, 2010
Last Updated
April 23, 2017
Sponsor
PETHEMA Foundation
search

1. Study Identification

Unique Protocol Identification Number
NCT01194791
Brief Title
Lendexal in Patients With Primary Systemic Amyloidosis (AL) Newly Diagnosed
Acronym
LENDEXAL
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2015
Overall Recruitment Status
Completed
Study Start Date
October 2010 (undefined)
Primary Completion Date
September 2012 (Actual)
Study Completion Date
December 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PETHEMA Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Systemic Amyloidosis
Keywords
Amyloidosis, Lenalidomide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Lenalidomide, Cyclophosphamide and Dexamenthasone
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
Lendexal
Intervention Description
Lenalidomide 15 mg by mouth for 21 days followed by 7 days rest during 6 cycles
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Cyclophosphamide 300 mg/m2, on days 1 and 8 every 4 weeks during 6 cycles
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Oral dexamethasone 20 mg/day on days 1-4 and 9-12 given at 4-week intervals during 6 cycles
Primary Outcome Measure Information:
Title
Hematologic response rate to the association of Lenalidomide, Cyclophosphamide and Dexamethasone
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Organ response rate
Time Frame
6 months
Title
Predictors of response (cardiac biomarkers, serum free light chains)
Time Frame
5 years
Title
Safety and tolerability
Time Frame
5 years
Title
Duration of response
Time Frame
10 years
Title
Time to progression
Time Frame
5 years
Title
Overall survival
Time Frame
10 yeras

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. 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. Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bladé Joan, Dr
Organizational Affiliation
Hospital Clinic of Barcelona
Official's Role
Study Chair
Facility Information:
Facility Name
Hospital Universitario de Canarias
City
Tenerife
State/Province
Islas Canarias
Country
Spain
Facility Name
Hospital Germans Trias i Pujol
City
Badalona
Country
Spain
Facility Name
Hospital Clínic
City
Barcelona
Country
Spain
Facility Name
Hospital de la Santa Creu i Sant Pau
City
Barcelona
Country
Spain
Facility Name
Hospital Clínico San Carlos
City
Madrid
Country
Spain
Facility Name
Hospital Doce de Octubre
City
Madrid
Country
Spain
Facility Name
Hospital Morales Messeguer
City
Murcia
Country
Spain
Facility Name
Hospitalm Clínico de Salamanca
City
Salamanca
Country
Spain
Facility Name
Hospital La Fe
City
Valencia
Country
Spain
Facility Name
Hospital Lozano Blesa
City
Zaragoza
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
25974382
Citation
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.
Results Reference
derived
Links:
URL
http://aehh.org
Description
Spanish Haematology Association
URL
http://seif88.com
Description
CRO

Learn more about this trial

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

We'll reach out to this number within 24 hrs