A Trial of Treatment With Lenalidomide-Melphalan-Dexamethasone in Patients With Primary (AL) Amyloidosis (LEOMEX)

This study has been completed.
Sponsor:
Collaborator:
Gesellschaft für Medizinische Innovation - Hämatologie und Onkologie mbH
Information provided by (Responsible Party):
Dr. Stefan Schönland, University of Heidelberg
ClinicalTrials.gov Identifier:
NCT00883623
First received: April 15, 2009
Last updated: November 21, 2013
Last verified: November 2013
  Purpose

The treatment with oral melphalan and prednisone has been recommended as standard treatment of AL amyloidosis but the results are rather disappointing. Another therapeutic option is pulsed high-dose dexamethasone + melphalan (Mel-Dex) with more encouraging results regarding the achievement of a faster disease response and higher rates of haematological remission. In the last 5 - 10 years, promising treatment outcomes after therapy with high-dose melphalan and autologous stem cell support have been reported by several groups but only highly selected patients are eligible for this treatment. Lenalidomide has been shown to be effective in phase II and III trials in MM patients. Because of the relationship to MM, Lenalidomide is a promising therapeutic option also for patients with AL amyloidosis. The addition of Lenalidomide to Mel-Dex could improve rate of complete response (CR) and organ response in patients not eligible for or refused high-dose chemotherapy.


Condition Intervention Phase
Primary Amyloidosis
Drug: Lenalidomide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective Single Center Trial of Treatment With Lenalidomide-Melphalan-Dexamethasone in Patients With AL Amyloidosis

Resource links provided by NLM:


Further study details as provided by Heidelberg University:

Primary Outcome Measures:
  • Complete response (CR) rate [ Time Frame: 6 months: after 6 cycles of L-Mel-Dex ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Rate of hematological response (CR and PR) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Organ response rate [ Time Frame: 3 months after discontinuation of L-Mel_Dex (maximum: 9 months) ] [ Designated as safety issue: No ]
  • Correlation of cytogenetic aberrations and gene expression profiling (GEP) results with best hematological response to treatment [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Retrospective comparison with a historical control group treated with Mel-Dex in our institution [ Time Frame: 01.04.2012 ] [ Designated as safety issue: No ]
  • Toxicity (hematological and non-hematological) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Enrollment: 50
Study Start Date: April 2009
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Arm
Treatment Arm
Drug: Lenalidomide
Up to 6 cycles of oral L-Mel-Dex, every 28 days Revlimid® 10 mg daily for 21 days, (add on therapy), Melphalan 0.15 mg/kg/day day 1-4, Dexamethasone 20 mg day 1-4
Other Name: Revlimid

  Eligibility

Ages Eligible for Study:   18 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Biopsy proven systemic untreated AL amyloidosis requiring systemic chemotherapy
  • Not eligible for or refused HDM
  • Measurable plasma cell disease
  • Life expectancy > 3 months
  • WHO performance status < 3
  • NYHA < stage IV
  • Understand and voluntarily sign an informed consent form
  • Laboratory test results within these ranges Absolute neutrophil count > 1.5 x 109/L Platelet count > 100 x 109/L Creatinine Clearance / MDRD > 40 ml/min Total bilirubin > 2,5 mg/dL
  • Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study; and 3) for at least 28 days after discontinuation from the study.

Exclusion Criteria:

  • Multiple Myeloma stage II and III (Durie and Salmon)
  • Previous organ transplantation
  • Not able to visit the Amyloid Clinic in Heidelberg once per month
  • Refusal of aspiration of 100 ml bone marrow at study inclusion
  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
  • Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
  • Use of any other experimental drug or therapy within 28 days of baseline.
  • Known hypersensitivity to thalidomide.
  • The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
  • Any prior use of lenalidomide.
  • Concurrent use of other anti-cancer agents or treatments.
  • Known positive for HIV or infectious hepatitis, B or C.
  • Patients who are in a depending position of the Sponsor or the Principal Investigator
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00883623

Locations
Germany
University Clinic Heidelberg
Heidelberg, Germany, 69120
Sponsors and Collaborators
Heidelberg University
Gesellschaft für Medizinische Innovation - Hämatologie und Onkologie mbH
Investigators
Principal Investigator: Stefan Schoenland, MD University Clinic Heidelberg - Department of Internal Medicine V
  More Information

Additional Information:
No publications provided

Responsible Party: Dr. Stefan Schönland, MD, University of Heidelberg
ClinicalTrials.gov Identifier: NCT00883623     History of Changes
Other Study ID Numbers: 2008-001405-41, GMIHO 005/2007 (191063)
Study First Received: April 15, 2009
Last Updated: November 21, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Heidelberg University:
AL-Amyloidosis
Lenalidomide

Additional relevant MeSH terms:
Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Lenalidomide
Melphalan
Thalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on July 24, 2014