Celgene High Risk Multiple Myeloma (MM) Revlimid Induction and Maintenance Therapy

NCT00691704 | Completed Phase 2 Results

• 1 other identifier: Pro00002869
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the effectiveness of induction therapy with lenalidomide and low dose dexamethasone followed by sequential low dose bortezomib followed by low dose Melphalan and Prednisone, then followed by low dose lenalidomide for multiple cycles in subjects with high risk Multiple Myeloma (MM). The primary objective is to evaluate the efficacy as measured by the progression free survival (PFS) at 2 years of low dose sequential therapy following four cycles of induction therapy with lenalidomide/low-dose dexamethasone in subjects with symptomatic high risk multiple myeloma, who have received no prior treatment. A total of 35 subjects were estimated to be accrued to this Phase II trial over a period of subjects who are still progression-free at 2 years. Two years will be as measured from date of registration to the trial. Progression will include disease progression (DP) as well as death due to any cause. Data will be analyzed and reported by the PI after 1 and 2 years of initiation of the study. All subsequent data collected may be analyzed and reported in a follow-up clinical report. The PI and independent reviewers will meet to review the efficacy and safety data and determine a risk/benefit analysis in this subject population.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Progression free survival (PFS) is defined for all subjects as the time from the date of initiation of treatment to the date of first documentation of relapse, progression, or death due to any cause. Full restaging was performed at 6, 12, 18, 24, 36, 48, 60, 72 months). PFS survival will be estimated and plotted with the Kaplan-Meier method. The median will be calculated with 95% confidence intervals.

  2 years

Secondary Outcomes (4)

• Time to Response

  6 months

• Overall Survival

  6 years

• Time to Progression

  6 years

• Duration of Response

  6 years

Study Arms (1)

High-risk Multiple Myeloma

EXPERIMENTAL

Lenalidomide Induction (with Low Dose Dexamethasone) Therapy Followed by Low Dose Melphalan, Prednisone, Lenalidomide and Bortezomib Sequential Maintenance Therapy

Drug: Lenalidomide Induction; Drug: Sequential Maintenance Therapy

Interventions

Lenalidomide Induction DRUG

Induction: Lenalidomide 25 mg daily on Days 1-21 followed by 7 day rest and Dexamethasone 40 mg by mouth (po) daily on Days 1, 8, 15 and 22 every 28 days for 4 cycles.

Also known as: Lenalidomide

High-risk Multiple Myeloma

Sequential Maintenance Therapy DRUG

Subjects who achieve \>partial response (PR) following induction therapy will receive repeating triplet cycles of alternating low dose therapy until progression, poor tolerance or toxicity. Subjects who complete 24 months of maintenance will be removed from study unless they achieved \> stable disease (SD) from maintenance (per discussion with physician): * 325 mg aspirin for deep vein thrombosis (DVT) prophylaxis * Cycle 1, 4, 7, etc. - bortezomib 1.3 mg/m2 on day 1 and 8 of a 28-day cycle * Cycle 2, 5, 8 etc. - Melphalan 6 mg/m2 by mouth (po) daily on Days 1-7 * Prednisone 60 mg /m2 po daily on Days 1-7 of a 28-day cycle * Cycle 3, 6, 9, etc. Lenalidomide 10 mg po daily on Days 1-21 of a 28 day cycle.

Also known as: Lenalidomide (Revlimid), Bortezomib (Velcade), Melphalan, Prednisone, Aspirin

High-risk Multiple Myeloma

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 or older at the time of signing the consent.
• Able to adhere to the study visit schedule and other protocol requirements.
• Multiple myeloma (MM) diagnosed according to the following standard criteria:
• Monoclonal plasma cells in bone marrow ≥10% and/or presence of biopsy-proven plasmacytoma
• Monoclonal protein present in serum and/or urine Myeloma-related organ dysfunction (1 or more) (C) Calcium elevation in blood (serum calcium \>10.5 mg/L or ULN) (R) Renal insufficiency (SCr \>2 mg/dL) (A) Anemia (hemoglobin \<10 g/dL or 2g \<normal) (B) Lytic bone lesions or osteoporosis
• Measurable disease requiring systemic therapy.
• High risk multiple myeloma defined by the presence of one or more of the following:
• Deletion of chromosome 13 by metaphase analysis (standard cytogenetics)
• deletion of 17p13 (p53) by Fluorescence in situ hybridization (FISH) or metaphase analysis
• t(4;14) by FISH
• t(14;16) by FISH
• t(8;14) by FISH
• t(14;20) by FISH
• hypodiploidy detected by FISH or metaphase analysis

You may not qualify if:

• Any serious medical condition, laboratory abnormality, or psychiatric illness to prevent the subject from signing the consent.
• Pregnant or breast feeding females.
• Any condition which places the subject at unacceptable risk or confounds the ability to interpret data from the study.
• Abnormal laboratory test results within these ranges:
• Absolute neutrophil count \< 1.0 x 109/L
• Platelet count \< 50 x 109/L (Subjects with severe pancytopenia (not meeting the above criteria) due to myeloma involvement of \> 70% bone marrow are eligible)
• Serum creatinine \> 2.5 mg/dL or ≥ 3.0 mg/dL if due to multiple myeloma.
• Total bilirubin \> 2.0 mg/dl
• History of allergy to any of the study medications, their analogues, or excipients in the various formulations
• Concurrent use of other anti-cancer agents or treatments.
• Known HIV positivity
• Known Active Hepatitis A, B or C
• Erythema nodosum characterized by a desquamating rash while taking thalidomide or similar drug.

Sponsors & Collaborators

• Cristina Gasparetto: lead
• Celgene Corporation: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Lenalidomide; Bortezomib; Melphalan; Prednisone; Aspirin

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

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; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic

Results Point of Contact

• Title: Cristina Gasparetto, MD
• Organization: Duke University Medical Center

cristina.gasparetto@duke.edu

919-668-1017

Study Officials

• Cristina Gasparetto, MD

  Duke University

  PRINCIPAL INVESTIGATOR

• David Hurd, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

• Peter M Voorhees, MD

  UNC Hospitals, University of North Carolina - Chapel Hill

  PRINCIPAL INVESTIGATOR

• Jeffrey A. Zonder, MD

  Karmanos Cancer Center, Wayne State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: June 3, 2008
• First Posted: June 5, 2008
• Study Start: August 1, 2008
• Primary Completion: December 1, 2012
• Study Completion: May 1, 2014
• Last Updated: August 19, 2014
• Results First Posted: April 10, 2014

Record last verified: 2014-08

Locations

US (1)