Bortezomib, Doxorubicin Hydrochloride Liposome, and Dexamethasone Followed by Thalidomide and Dexamethasone With or Without Bortezomib in Treating Patients With Multiple Myeloma

NCT00458705 | Completed Phase 2 Results

• 3 other identifiers: 06-067P30CA008748MSKCC-06067
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as doxorubicin hydrochloride liposome and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or stopping them from dividing. Thalidomide may stop the growth of cancer cells by blocking blood flow to the cancer. Giving bortezomib together with doxorubicin hydrochloride liposome and dexamethasone followed by thalidomide, dexamethasone, and bortezomib may kill more cancer cells. PURPOSE: This phase II trial is studying the side effects and how well giving bortezomib together with doxorubicin hydrochloride liposome and dexamethasone followed by thalidomide and dexamethasone with or without bortezomib works in treating patients with multiple myeloma.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; refractory multiple myeloma

Outcome Measures

Primary Outcomes (1)

• Disease Response

  The response of myeloma to BDDTD will be assessed by standard electrophoretic and immunofixation tests of blood and urine for a monoclonal protein (M protein), and bone marrow aspirate and biopsy. These tests will be performed at enrollment and at the conclusion of therapy.

  2 years

Study Arms (1)

Combination therapy

EXPERIMENTAL

Combination therapy with bortezomib, pegylated liposomal doxorubicin and dexamethasone (BDD) followed by either thalidomide and dexamethasone (TD) or bortezomib, thalidomide and dexamethasone in patients with symptomatic untreated high-risk or primary resistant multiple myeloma. Three cycles of BDD will be administered. Patients who respond after three cycles will receive two cycles of TD. Patients with stable or progressive disease after three cycles of BDD receive two cycles of bortezomib, thalidomide and dexamethasone. If at any point during the study a patient achieves a complete response (CR), the patient will be given the option to discontinue treatment on-study.

Drug: bortezomib; Drug: dexamethasone; Drug: pegylated liposomal doxorubicin hydrochloride; Drug: thalidomide

Interventions

bortezomib DRUG

Combination therapy

dexamethasone DRUG

Combination therapy

pegylated liposomal doxorubicin hydrochloride DRUG

Combination therapy

thalidomide DRUG

Combination therapy

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically and serologically confirmed multiple myeloma meeting one of the following criteria: * High-risk myeloma, defined as symptomatic International Staging System (ISS) stage 2 or 3 multiple myeloma * Soft-tissue involvement with myeloma in the form of a soft-tissue plasmacytoma * Extension of a plasmacytoma into soft tissues * Primary resistant myeloma, defined as unchanged or progressive myeloma despite two courses of standard treatment * No ISS stage 1 multiple myeloma without soft-tissue involvement * No smoldering myeloma PATIENT CHARACTERISTICS: * ECOG performance status 0-3 * Life expectancy \> 16 weeks * Absolute granulocyte count ≥ 1,500/mm³ (unless low granulocyte counts are due to multiple myeloma) * Platelet count ≥ 100,000/mm³ (unless low platelet counts are due to multiple myeloma) * Bilirubin ≤ 2.0 mg/dL * AST and ALT \< 3 times upper limit of normal (ULN) * Alkaline phosphatase \< 3 times ULN * LVEF ≥ 50% by MUGA or ECHO * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier contraception 4 months prior to, during, and for 4 weeks after completion of study treatment * No active thromboembolic disease on anticoagulation * No active angina or myocardial infarction within the past 6 months * No pre-existing neuropathy or sensory or neuropathic pain ≥ grade 2 * No concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix * Prior malignancies that have not required antitumor treatment within the past 24 months allowed * Patients with a history of stage I or II (T1a/b) prostate cancer (detected incidentally at transurethral resection of prostate \[TURP\] and comprising \< 5% of resected tissue) allowed if the prostate-specific antigen has remained normal since TURP * No known HIV positivity or AIDS-related illness * No other medical condition or reason that, in the opinion of the investigator, would preclude study compliance * No history of hypersensitivity reactions attributed to a conventional formulation of doxorubicin hydrochloride or to components of pegylated doxorubicin hydrochloride liposome, bortezomib, boron, or mannitol PRIOR CONCURRENT THERAPY: * Prior radiotherapy allowed * No more than 2 courses of prior initial chemotherapy for multiple myeloma * No prior bortezomib * No prior high-dose steroids (not including taper) for more than 1 month in duration for emergent indications, such as hypercalcemia or life-threatening lesions (e.g., spinal cord compromise) (in high-risk patients)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• Landau H, Pandit-Taskar N, Hassoun H, Cohen A, Lesokhin A, Lendvai N, Drullinsky P, Schulman P, Jhanwar S, Hoover E, Bello C, Riedel E, Nimer SD, Comenzo RL. Bortezomib, liposomal doxorubicin and dexamethasone followed by thalidomide and dexamethasone is an effective treatment for patients with newly diagnosed multiple myeloma with Internatinal Staging System stage II or III, or extramedullary disease. Leuk Lymphoma. 2012 Feb;53(2):275-81. doi: 10.3109/10428194.2011.606943. Epub 2011 Sep 23.

  PMID: 21824051 RESULT

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Bortezomib; Dexamethasone; Thalidomide

Condition Hierarchy (Ancestors)

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)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Heather Landau
• Organization: Memorial Sloan Kettering Cancer Center

landauh@mskcc.org

212-639-8808

Study Officials

• Heather Landau, MD

  Memorial Sloan Kettering Cancer Center

  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

Study Record Dates

• First Submitted: April 9, 2007
• First Posted: April 11, 2007
• Study Start: November 1, 2006
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: January 22, 2016
• Results First Posted: January 22, 2016

Record last verified: 2015-12

Locations

US (1)