Pegylated Liposomal Doxorubicin, Bortezomib, Dexamethasone and Lenalidomide for Relapsed/Refractory Multiple Myeloma

NCT01160484 | Completed Phase 2 Results

• 1 other identifier: RV-MM-PI-0533
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 8

Brief Summary

This is a phase II, multicenter, open label, nonrandomized study to evaluate the efficacy and safety of lenalidomide at a dose of 10 mg/dose in combination with bortezomib at 1.0 mg/m2/dose, pegylated liposomal doxorubicin (PLD) at 4.0 mg/m2/dose, and intravenous (IV) dexamethasone at 40 mg/dose in adult patients with relapsed/refractory multiple myeloma (MM). The study consists of a screening period, followed by up to eight 28 day open label treatment cycles, a final assessment to occur 28 days after the end of the last treatment cycle, and a follow-up period.

Conditions

Multiple Myeloma

Keywords

multiple myeloma; refractory; relapsed; bortezomib; doxil

Outcome Measures

Primary Outcomes (1)

• International Myeloma Working Group (IMWG) Response Criteria

  The investigator will evaluate each patient for response to therapy according to criteria augmented from those developed by Bladé et al., 1998 presented below (Table 7-1). Assessment of disease response will be performed prior to drug administration on Day 1 of Cycles 2 8 and at the End of Study Treatment visit. If a patient is determined to have complete response (CR), very good partial response (VGPR), partial response (PR), or minor response (MR), then assessment of disease response is to be performed 4 weeks later to confirm the response.

  Up to 7.5 months (eight 28-day cycles)

Secondary Outcomes (6)

• Time to First Response

  Up to 7.5 months (eight 28-day cycles)

• Time to Best Response

  Up to 7.5 months (eight 28-day cycles)

• Duration of Response

  First evidence of PR or better (for overall response) and MR or better (for clinical benefit response) to start of disease progression or death.

• Time to Progression

  Time from the start of treatment to progressive disease

• Progression-free Survival

  Time from the start of treatment to progressive disease or until death

Study Arms (1)

DVD-R single arm

EXPERIMENTAL

Dose schematic of Dexamethasone + Bortezomib + Pegylated Liposomal Doxorubicin + Lenalidomide (DVD-R) Therapy: Dexamethasone\*- 40 mg IV Bortezomib\*\*- 1.0 mg/m2 IV Push Pegylated Liposomal Doxorubicin\*- 4.0 mg/m2 IV Lenalidomide\*\*\*- 10 mg PO Per 28 Day Cycle * Intravenous infusion (IV) Days 1, 4, 8 and 11 \*\* Intravenous push (IVP) Days 1, 4, 8 and 11 \*\*\* Per Orem (PO) Days 1-14

Drug: DVD-R

Interventions

DVD-R DRUG

40 mg dexamethasone will be administered IV on Days 1, 4, 8, and 11 of each cycle. 1.0 mg/m2 Bortezomib will be administered IV over 3 to 5 seconds followed by a standard saline flush, on Days 1, 4, 8, and 11 immediately following the dexamethasone infusion. 4.0 mg/m2 PLD will be given as a 90 minute infusion on Day 1 of Cycle 1 and subsequent doses may be administered over 30 to 60 minutes on Days 4, 8 and 11 of Cycle 1 and on Days 1, 4, 8, and 11 of each subsequent cycle, following the bortezomib administration. 10 mg/day lenalidomide will be administered PO on days 1-14 of a 28-day treatment cycle, followed by a 14-day rest period, following the PLD administration.

Also known as: Decadron, Velcade, Doxil, Revlimid

DVD-R single arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has a diagnosis of multiple myeloma (MM) based on standard criteria (Durie 1986)
• Currently has MM with measurable disease (serum m protein \> 1.0g/dl and/or 24 hr urine m protein \> 200mg/24 hr)
• Currently has progressive MM that has relapsed or is refractory
• Voluntarily signed an informed consent
• Age 18 years
• Eastern Cooperative Oncology Group (ECOG) performance \< 2
• Life-expectancy \> 3 months
• Laboratory test results within these ranges:
• Absolute neutrophil count (ANC) 1.5 x 109/L; if the bone marrow is extensively infiltrated (\> 70% plasma cells) then 1.0 x 109/L
• Platelet count 75 x 109/L; if the bone marrow is extensively infiltrated (\> 70% plasma cells) then 50 x 109/L
• Hg \> 8 g/dL
• Calculated or measured creatinine clearance \> 30 mL/minute.
• Total bilirubin 2.0 x upper limit of normal (ULN)
• Aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) 3 x ULN or 5 x ULN if hepatic metastases are present
• Serum potassium within the normal range

You may not qualify if:

• Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes syndrome
• Plasma cell leukemia
• Grade 2 peripheral neuropathy within 14 days before enrollment
• Impaired cardiac function or clinically significant cardiac diseases, including myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) Class II or greater heart failure, Uncontrolled angina, clinically significant pericardial disease, severe uncontrolled ventricular arrhythmias, echocardiogram or Multigated acquisition(MUGA) scan evidence of left ventricular ejection fraction (LVEF) below institutional normal within 28 days prior to enrollment, electrocardiographic (ECG) evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
• Severe hypercalcemia, i.e., serum calcium 12 mg/dL (3.0 mmol/L) corrected for albumin
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
• 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
• Undergone major surgery within 28 days prior enrollment or has not recovered from side effects of such therapy (Kyphoplasty is not considered to be a major surgery; however, the investigator is to discuss enrollment of a patient with a recent history of kyphoplasty with the medical monitor).
• Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide)
• Received the following prior therapy:
• Chemotherapy within 3 weeks of enrollment (6 wks for nitrosoureas)
• Corticosteroids (\>10 mg/day prednisone or equivalent) within 3 weeks of enrollment
• Immunotherapy or antibody therapy as well as thalidomide, lenalidomide, arsenic trioxide or bortezomib within 21 days before enrollment
• Radiation therapy within 28 days before enrollment, except localized radiation therapy
• Use of any other experimental drug or therapy within 28 days of enrollment

Sponsors & Collaborators

• Oncotherapeutics: lead
• Celgene Corporation: collaborator

Study Sites (8)

Comprehensive Blood and Cancer Center

Bakersfield, California, 93309, United States

Location

Hematology-Oncology Medical Group of Fresno, Inc.

Fresno, California, 93720, United States

Location

Loma Linda University

Loma Linda, California, 92354, United States

Location

Santa Barbara Hematology Oncology

Santa Barbara, California, 93105, United States

Location

James R. Berenson, M.D., Inc.

West Hollywood, California, 90069, United States

Location

Watson Clinic, LLP, Center for Care and Research

Lakeland, Florida, 33805, United States

Location

Bassett Cancer Institute

Cooperstown, New York, 13326, United States

Location

Broome Oncology

Johnson City, New York, 13790, United States

Location

Related Publications (1)

• Berenson JR, Yellin O, Kazamel T, Hilger JD, Chen CS, Cartmell A, Woliver T, Flam M, Bravin E, Nassir Y, Vescio R, Swift RA. A phase 2 study of pegylated liposomal doxorubicin, bortezomib, dexamethasone and lenalidomide for patients with relapsed/refractory multiple myeloma. Leukemia. 2012 Jul;26(7):1675-80. doi: 10.1038/leu.2012.51. Epub 2012 Feb 22.

  PMID: 22354206 RESULT

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

Calcium Dobesilate; Bortezomib; liposomal doxorubicin; Lenalidomide

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Director, Clinical Operations
• Organization: Oncotherapeutics

lthulin@oncotherapeutics.com

323-623-1200

Study Officials

• James R. Berenson, MD

  James R. Berenson, MD, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2010
• First Posted: July 12, 2010
• Study Start: September 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: September 1, 2012
• Last Updated: May 4, 2015
• Results First Posted: April 21, 2014

Record last verified: 2015-04

Locations

US (8)