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Lenalidomide in Combination With Melphalan and Dexamethasone in Newly-Diagnosed Light-Chain (AL)-Amyloidosis
This study is currently recruiting participants.
Verified by Nantes University Hospital, February 2009
First Received: February 12, 2008   Last Updated: February 10, 2009   History of Changes
Sponsored by: Nantes University Hospital
Information provided by: Nantes University Hospital
ClinicalTrials.gov Identifier: NCT00621400
  Purpose

Amyloidosis results from tissue deposition of amyloid protein, composed mainly by the fragments of monoclonal immunoglobulin heavy chains or light chains. Accumulation of amyloid protein progressively disrupts normal tissue structure and ultimately leads to organ failure, most frequently in the kidneys, heart, liver and peripheral nervous system. A recently completed French prospective randomized trial, in patients presenting with newly AL-amyloidosis, compared two treatment regimens at the time of diagnosis: Melphalan-dexamethasone (conventional oral treatment), versus high dose of Melphalan followed by autologous stem cell transplantation (ASCT) (1). High-dose therapy was not associated with a better outcome. Melphalan-dex given monthly can be considered as the current standard of care, with a median survival of 56 months. The use of a combination of lenalidomide and dexamethasone has already been tested in patients with AL-amyloidosis (2). The initial dose of lenalidomide at 25 mg/day was poorly tolerated. However, a 15 mg/day dose regimen was well tolerated and effective, with an overall hematologic response rate of 67%. Hematologic responses were associated with clinical responses. Dispenzieri et al confirmed that the combination of Lenalidomide + dexamethasone achieved a 75% hematologic response rate, with a 42% organ response, and a median follow-up of 17 months in patients still receiving treatment (2006). These authors also recommended a lower dose of 15mg/day. The rationale for the present investigation is that addition of lenalidomide to the current standard of care (Melphalan-dexamethasone) might improve the hematologic response rate and the organ response rates both associated with a prolonged survival in patients with AL-amyloidosis. As the toxicity of the combination of M-dex + lenalidomide is unknown in patients with AL-amyloidosis, the dose of lenalidomide will start from the lowest one available, i.e., 5 mg/day and increased from 5 to 5 mg up to a maximum dose of 15 mg in combination with M-dex in 3 consecutive cohorts of patients, according to toxicity. When the optimal dose of lenalidomide will be defined, 9 additional patients will be included in the trial at the recommended dose-level to assess the feasibility of the combination M-dex-lenalidomide.


Condition Intervention Phase
Amyloidosis
Drug: Lenalidomide
Drug: Melphalan
Drug: Dexamethasone
Phase I
Phase II

Drug Information available for: Dexamethasone Dexamethasone acetate Doxiproct plus Lenalidomide CC 5013 Melphalan Sarcolysin Dexamethasone Sodium Phosphate Melphalan hydrochloride
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title: A Multicenter Phase I/II Dose Escalation Study of Lenalidomide in Combination With Melphalan and Dexamethasone in Subjects With Newly-Diagnosed Light-Chain (AL)-Amyloidosis

Further study details as provided by Nantes University Hospital:

Primary Outcome Measures:
  • The primary endpoint is to evaluate the incidence of dose limiting toxicities (DLT) during the first cycle of lenalidomide at a given dose level in order to determine the maximal tolerated dose (MTD) in a dose escalating study design.

Secondary Outcome Measures:
  • To determine the hematologic response, the rate of organ response, explore the value of frequent measurements of free light chain assays, assess the safety profile of the combination therapy

Estimated Enrollment: 42
Study Start Date: January 2008
Estimated Study Completion Date: August 2010
Estimated Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Lenalidomide
    5 mg/day, orally for 21 days with 7 days rest (28 day cycle) for the first cohort; or 10mg/day, orally for 21 days with 7 days rest (28 day cycle) for the second cohort, 15mg/day, orally for 21 days with 7 days rest (28 day cycle) for the third cohort or 20mg/day, orally for 21 days with 7 days rest (28 day cycle) for the last and fourth cohort
    Drug: Melphalan
    0,18mg/Kg/day from day 1- 4
    Drug: Dexamethasone
    40mg/day from day 1- 4.
  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • De novo systemic biopsy proven AL-amyloidosis.
  • Measurable organ site involvement consistent with the diagnosis.
  • Adequate organ function defined as

    • Absolute neutrophil count > 1.0 x 109/L;
    • platelet count > 100x109/L;
    • AST (SGOT) and ALT (SGPT) < 2 x UNL;
    • Total bilirubin £ 1.5 mg/dL ;
    • creatinin serum level <150µmol/L (1.5mg/dl);
  • Evaluable immunochemical abnormalities, including abnormal serum free light chain assay with an increase of either kappa or lambda light chain level.
  • ECOG performance status of £ 2 at study entry (see Appendix BB).
  • Age between18 and 70 years at the time of signing the informed consent form.
  • Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL at screening visit and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. See Appendix: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.
  • Able to understand and voluntarily sign an informed consent form.
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Able to take antithrombotic medicines such as low molecular weight heparin or warfarin (if needed).
  • Disease free of prior malignancies for > 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
  • Subjects affiliated with an appropriate social security system.

Exclusion Criteria:

  • Symptomatic multiple myeloma: multiple myeloma with related organ of tissue impairment (ROTI) according to the International Myeloma Working Group (16)
  • Any other uncontrolled medical condition or comorbidity that might interfere with subject's participation.
  • Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
  • Use of any other experimental drug or therapy within 28 days of baseline.
  • The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
  • Any prior treatment for amyloidosis.
  • Known positive for HIV or infectious hepatitis, type A, B or C.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00621400

Contacts
Contact: Philippe Moreau, MD philippe.moreau@chu-nantes.fr

Locations
France
CHU de Nantes Recruiting
Nantes, France, 44093
Contact: Philippe Moreau, MD            
CHU de Limoges Recruiting
Limoges, France, 87042
Contact: Arnaud Jaccard, MD            
Hôpital Saint-Louis Not yet recruiting
Paris, France, 75475
Contact: Jean-Paul Fermand, MD            
Hôpital Pitié Salpetrière Not yet recruiting
Paris, France, 75651
Contact: Véronqiue Leblond, MD            
CHU de Rennes Not yet recruiting
Rennes, France, 35203
Contact: Bernard Grosbois, MD            
CHRU deTours Not yet recruiting
Tours, France, 37044
Contact: Lofti Benboubker, MD            
Hôpital necker Not yet recruiting
Paris, France, 75743
Contact: Olivier Hermine, MD            
CHU de Toulouse Not yet recruiting
Toulouse, France, 31059
Contact: Michel Attal, MD            
CHRU de Lille Not yet recruiting
Lille, France, 59037
Contact: Thierry Facon, MD            
CHRU d'Amiens Not yet recruiting
Amiens, France, 80054
Contact: Bruno Royer, MD            
CHU de Poitiers Not yet recruiting
Poitiers, France, 86021
Contact: franck Bridou, MD            
Hôpitaux Civils de Lyon Not yet recruiting
Pierre-Bénite, France, 69495
Contact: Catherine Traullé, MD            
Sponsors and Collaborators
Nantes University Hospital
  More Information

No publications provided

Responsible Party: Cellule Promotion Recherche Clinique ( Anne Omnes )
Study ID Numbers: BRD 07/7-G, EudraCT 2007-004739-43
Study First Received: February 12, 2008
Last Updated: February 10, 2009
ClinicalTrials.gov Identifier: NCT00621400     History of Changes
Health Authority: France: Afssaps - French Health Products Safety Agency

Keywords provided by Nantes University Hospital:
newly-diagnosed light-chain (AL)-amyloidosis

Study placed in the following topic categories:
Anti-Inflammatory Agents
Dexamethasone
Melphalan
Metabolic Diseases
Immunologic Factors
Antineoplastic Agents, Hormonal
Hormone Antagonists
Lenalidomide
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Immunosuppressive Agents
Glucocorticoids
Hormones
Amyloidosis
Antineoplastic Agents, Alkylating
Peripheral Nervous System Agents
Alkylating Agents
Metabolic Disorder
Dexamethasone acetate

Additional relevant MeSH terms:
Dexamethasone
Anti-Inflammatory Agents
Melphalan
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Hormones
Therapeutic Uses
Alkylating Agents
Dexamethasone acetate
Metabolic Diseases
Antineoplastic Agents, Hormonal
Lenalidomide
Gastrointestinal Agents
Glucocorticoids
Immunosuppressive Agents
Pharmacologic Actions
Amyloidosis
Autonomic Agents
Myeloablative Agonists
Peripheral Nervous System Agents
Antineoplastic Agents, Alkylating
Central Nervous System Agents

ClinicalTrials.gov processed this record on May 06, 2009