Study of Vorinostat With Doxil and Bortezomib for Patients With Relapsed/Refractory Multiple Myeloma

NCT01492881 | Withdrawn Phase 2 DMC

• 1 other identifier: LCCC 1119
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to determine how multiple myeloma responds when the study drug vorinostat is added to the standard treatment of bortezomib and pegylated liposomal doxorubicin (PLD). After participants complete the three drug combination and if their multiple myeloma has decreased, the investigators also want to learn what effects (both good and bad) when vorinostat and bortezomib are given to people with multiple myeloma over a longer period of time. This type of treatment is called 'Maintenance Therapy'.

Conditions

Multiple Myeloma

Keywords

relapsed multiple myeloma; refractory multiple myeloma; vorinostat; bortezomib; doxil

Outcome Measures

Primary Outcomes (1)

• Estimate the overall response rate.

  Estimate the overall response rate (ORR) of the vorinostat, PLD and bortezomib regimen (VB/PLD) followed by vorinostat/bortezomib (VB) maintenance in patients with relapsed and relapsed/refractory multiple myeloma. Criteria for response will be based on the International Uniform Response Criteria for Multiple Myeloma, modified to incorporate criteria for minor response (MR). The overall response rate will be defined as the total number of patients whose response are PR or above, divided by the number of response evaluable patients.

  18 months

Secondary Outcomes (4)

• Evaluate the quality of life measures in patients.

  18 months

• Assess the safety and tolerability.

  18 months

• Estimate the overall survival.

  36 months

• Estimate Progression-free survival

  36 months

Study Arms (1)

Vorinostat, Bortezomib, Doxil

EXPERIMENTAL

Induction therapy will consist of up to 8 cycles of vorinostat, bortezomib, and doxil. One cycle is defined as 21 days. Maintenance therapy will consist of Vorinostat and bortezomib. One maintenance cycle is 28 days and repeated for up to 1 year.

Drug: Vorinostat; Drug: Bortezomib; Drug: pegylated liposomal doxorubicin

Interventions

Vorinostat DRUG

Oral, 400mg, taken days 4 through 11 of each cycle.

Also known as: Zolina

Vorinostat, Bortezomib, Doxil

Bortezomib DRUG

subcutaneous injection, 1.3mg/m2, Days 1, 4, 8, and 11 every cycle

Also known as: Velcade

Vorinostat, Bortezomib, Doxil

pegylated liposomal doxorubicin DRUG

Intravenous, 30mg/m2, Day 4

Also known as: Doxil

Vorinostat, Bortezomib, Doxil

Eligibility Criteria

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

You may qualify if:

• Relapsed or relapsed and refractory multiple myeloma:
• Relapsed MM is defined as clinically active disease, in patients who have received one or more prior therapies, that is not refractory to the most recent treatment. (Refractory to the prior treatment means either progressive disease (PD) on last prior therapy; best response of stable disease (SD) to last prior therapy, or PD within 60 days of completing therapy).
• Relapsed and refractory MM is defined as relapsed disease, which either becomes non-responsive while on salvage therapy, or progresses within 60 days of last therapy.
• to 3 prior lines of therapy for multiple myeloma (a single line of treatment may consist of 1 or more agents and regimens. A single line of therapy may be most easily delineated by a response to treatment followed by a change in treatment due to the progression of disease.
• Prior bortezomib- and anthracycline-based therapy is allowed; prior cumulative doxorubicin dose must be \<360 mg/m2 (or its equivalent)
• Prior autologous stem cell transplantation is allowed provided the patient is 3 months out from transplant and has recovered from any transplant-related toxicities (to baseline or grade 1 in severity)
• All prior treatment-related non-hematologic toxicities resolved to ≤Grade 1 (or baseline), not including alopecia
• Prior radiation therapy completed ≥2 weeks prior to day 1 of treatment Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Age ≥18 years
• Life expectancy of at least 6 months
• Adequate bone marrow function (without platelet or RBC transfusion support within one week of screening) as demonstrated by:
• Hemoglobin ≥ 8 g/dL (use of erythropoietin stimulating agent is OK)
• Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 (without granulocyte growth factor support)
• Platelet count ≥ 100,000/mm3 (≥75,000/mm3 in patients with ≥30% marrow involvement of MM who are felt to have thrombocytopenia primarily due to marrow infiltration of disease as opposed to diminished marrow reserves from prior therapy)
• Adequate hepatic and renal function as demonstrated by:

You may not qualify if:

• \> 3 prior lines of therapy for treatment of MM
• Receipt of prior allogeneic stem cell/bone marrow transplantation
• Primary refractory MM as defined by the ASH/FDA Workshop on Clinical Endpoints in Multiple Myeloma\[24\]
• Peripheral neuropathy (PN) ≥ grade 1 with pain or ≥grade 2 PN within 14 days prior to enrollment
• Known history of HIV, HBV or HCV infection
• Serum potassium ≤3.0 mmol/L or serum magnesium ≤1.6mg/dL that cannot be corrected with supplementation
• Known hypersensitivity to bortezomib or any of its components (boron, mannitol), vorinostat, doxorubicin, or any of the components of PLD; Patients with a history of reactions to other liposomal drug formulations will be evaluated individually, and if their reactions were felt to have been due to the liposome itself, as opposed to the encapsulated agent, they will be excluded at the discretion of the investigators.
• Prior or concomitant use of a histone deacetylase inhibitor (exception: prior valproic acid for epilepsy is allowed provided patient undergoes a 30 day wash out prior to D1 of study treatment)
• No major surgery within 3 weeks prior to day 1 of study treatment
• Active, serious infection, medical, or psychiatric condition that would represent an inappropriate risk to the patient or would likely compromise achievement of the primary study objective
• Other prior or concomitant malignancies with the exception of:
• Non-melanoma skin cancer
• In-situ malignancy
• Low-risk prostate cancer after curative therapy
• Other cancer for which the patient has been disease free for ≥ 3 years

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Lineberger Comphrehensive Cancer Center at University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Related Links

• UNC Lineberger Comprehensive Cancer Center N.C. Cancer Hospital

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Vorinostat; Bortezomib; liposomal doxorubicin

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)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Peter M Voorhees, MD

  Lineberger Comprehensive Cancer Center at University of North Carolina at Chapel Hill

  PRINCIPAL INVESTIGATOR

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: December 12, 2011
• First Posted: December 15, 2011
• Study Start: April 1, 2012
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2017
• Last Updated: May 11, 2012

Record last verified: 2012-05

Locations

US (1)