Vorinostat, Bortezomib, and Doxorubicin Hydrochloride Liposome in Treating Patients With Relapsed or Refractory Multiple Myeloma

NCT00744354 | Terminated Phase 1 DMC

• 2 other identifiers: LCCC 071508-1073
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 4

Brief Summary

RATIONALE: Vorinostat and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Bortezomib may also stop the growth of multiple myeloma by blocking blood flow to the tumor. Drugs used in chemotherapy, such as doxorubicin hydrochloride liposome, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving doxorubicin hydrochloride liposome together with vorinostat and bortezomib may kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of vorinostat and to see how well it works when given together with bortezomib and doxorubicin hydrochloride liposome in treating patients with relapsed or refractory multiple myeloma.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of vorinostat

  4 years

Secondary Outcomes (2)

• Overall response rate

  5 years

• Duration of response

  5 years

Study Arms (1)

Non-Randomized Open Label Single Arm

EXPERIMENTAL

Phase 1 dose escalation trial of vorinostat in combination with bortezomib and pegylated liposomal doxorubicin hydrochloride.

Drug: bortezomib; Drug: pegylated liposomal doxorubicin hydrochloride; Drug: vorinostat

Interventions

bortezomib DRUG

Intravenous Push 1.3 mg/m2 Days 1, 4, 8, and 11

Also known as: Velcade

Non-Randomized Open Label Single Arm

pegylated liposomal doxorubicin hydrochloride DRUG

Intravenous infusion, 30mg/m2, Day 4, each cycle

Also known as: Doxil

Non-Randomized Open Label Single Arm

vorinostat DRUG

Oral, 300mg, Days 1, 2, 4, 5, 8, 9, 11, 12, every cycle.

Also known as: Zolinza

Non-Randomized Open Label Single Arm

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Diagnosis of multiple myeloma * Relapsed or refractory disease PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Life expectancy ≥ 3 months * ANC ≥ 1.0 x 10\^9/L (no granulocyte growth factor support, e.g., G-CSF or GM-CSF allowed) * Platelet count ≥ 100 x 10\^9/L (erythropoietin allowed, no platelet or RBC transfusion within the past 2 weeks) * Hemoglobin ≥ 8 g/dL (erythropoietin allowed, no platelet or RBC transfusion within the past 2 weeks) * Creatinine clearance ≥ 30 mL/min * AST or ALT ≤ 2.5 times upper limit of normal (ULN) * Total bilirubin ≤ 1.5 times ULN * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 3 months after completion of study treatment * LVEF ≥ 45% by MUGA or ECHO * Symptomatic neuropathy \< grade 2 * No known history of HIV * No active or serious infection, medical or psychiatric illness that would preclude study participation * No active hepatitis B or C infection * No other prior or concurrent malignancy except for adequately treated basal cell or squamous cell carcinoma of the skin, in situ malignancy, low-risk prostate cancer after curative therapy, or other cancer for which the patient has been disease-free for ≥ 3 years * No history of hypersensitivity reaction to bortezomib or any of its components (boron, mannitol), vorinostat, doxorubicin hydrochloride, or any of the components of PLD * No serum potassium ≤ 3.0 or serum magnesium ≤ 1.6 that cannot be corrected with supplementation are excluded * Patients must have adequate cardiovascular function, defined by all of the following: * No EKG evidence of active, clinically significant conduction system abnormalities * No EKG evidence of QTc prolongation \> grade 2 * NOTE: Any EKG abnormality at screening has to be documented by the investigator as not medically significant. PRIOR CONCURRENT THERAPY: * No limit to number of prior treatment regimens * At least 30 days since prior therapy and recovered * At least 3 months since prior autologous stem cell transplantation and recovered * Prior allogeneic stem cell or bone marrow transplantation allowed provided the following criteria are met: * More than 1 year since transplantation * No longer receiving immunosuppressive therapy or treatment for graft-versus-host disease (GVHD) prophylaxis * No active GVHD * No active, uncontrolled infections * No major surgery within the past 3 weeks * No prior anthracycline dose \> 360 mg/m\^2 for doxorubicin hydrochloride (including pegylated liposomal doxorubicin hydrochloride \[PLD\]) or 720 mg/m\^2 for epirubicin hydrochloride * No prior or concurrent histone deacetylase inhibitor (e.g., valproic acid) * No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) during course 1 * No other concurrent investigational or anticancer agent

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

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator
• Millennium Pharmaceuticals, Inc.: collaborator
• Ortho Biotech, Inc.: collaborator

Study Sites (4)

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

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

Chapel Hill, North Carolina, 27599-7295, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157-1096, United States

Location

Related Links

• Web address for UNC Lineberger Comprehensive Cancer Center

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Bortezomib; liposomal doxorubicin; Vorinostat

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; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Brandi Reeves, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2008
• First Posted: September 1, 2008
• Study Start: October 1, 2008
• Primary Completion: December 1, 2011
• Study Completion: April 1, 2015
• Last Updated: January 18, 2018

Record last verified: 2018-01

Locations

US (4)