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

Sponsors and Collaborators:	University of Heidelberg Gesellschaft für Medizinische Innovation - Hämatologie und Onkologie mbH
Information provided by:	University of Heidelberg
ClinicalTrials.gov Identifier:	NCT00883623

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 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 Prospective Single Center Trial of Treatment With Lenalidomide-Melphalan-Dexamethasone in Patients With AL Amyloidosis

Further study details as provided by University of Heidelberg:

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 ]

Estimated Enrollment:	50
Study Start Date:	April 2009
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	April 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Treatment Arm: Experimental 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

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

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

Contacts

Contact: Stefan Schoenland, MD	+49 (0) 6221 568001	stefan.schoenland@med.uni-heidelberg.de
Contact: Ute Hegenbart, MD	+49 (0) 6221 568001	ute.hegenbart@med.uni-heidelberg.de

Locations

Germany
University Clinic Heidelberg	Recruiting
Heidelberg, Germany, 69120
Contact: Stefan Schoenland, MD +49 (0) 6221 568001 stefan.schoenland@med.uni-heidelberg.de
Principal Investigator: Stefan Schoenland, MD

Sponsors and Collaborators

University of Heidelberg

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:

University Clinic Heidelberg - Department of Internal Medicine V This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	University Clinic Heidelberg - Department of Internal Medicine V ( Dr. med. Stefan Schönland )
Study ID Numbers:	2008-001405-41, GMIHO 005/2007 (191063)
Study First Received:	April 15, 2009
Last Updated:	April 17, 2009
ClinicalTrials.gov Identifier:	NCT00883623 History of Changes
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University of Heidelberg:

AL-Amyloidosis
Lenalidomide

Study placed in the following topic categories:

Anti-Inflammatory Agents
Dexamethasone
Melphalan
Metabolic Diseases
Immunologic Factors
Antineoplastic Agents, Hormonal
Hormone Antagonists
Primary Amyloidosis
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