Ph 2 Bortezomib, Dexamethasone, + Doxorubicin With ALCAR for Previously Treated Multiple Myeloma

Phase II Trial of Bortezomib, Low Dose Dexamethasone, and Doxorubicin With Acetyl-L-Carnitine for Neuroprotection in Patients With Previously Treated Multiple Myeloma

Patients will receive Bortezomib, Dexamethasone, and Doxorubicin in 21 day cycles a total of 4 to 8 times (based on response to the treatment). Patients will also receive acetyl-L-carnitine (ALCAR) daily.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Bort, Dex, and Dox with ALCAR

Detailed Description

The primary objective of this study is to assess overall response rate to the treatment.

Secondary objectives include: evaluating and describing the incidence of chemotherapy-induced peripheral neuropathy using the FACT/GOG-Ntx assessment tool; evaluating the utility of adding ALCAR to the chemotherapy to reduce the incidence of peripheral neuropathy; and evaluating the utility of the Grooved Pegboard Completion Time as a longitudinal measure of peripheral neuropathy.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Janesville, Wisconsin, United States
      • Mercy Health Systems
    • La Crosse, Wisconsin, United States
      • Gundersen Lutheran
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Cancer Center
    • Waukesha/Oconomowoc, Wisconsin, United States
      • Regional Cancer Center
    • Wausau, Wisconsin, United States
      • Aspirus Wausau Hospital, Aspirus Regional Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with previously treated multiple myeloma with measurable serum or urine monoclonal protein.

Exclusion Criteria:

• Patients with previous doxorubicin treatment totaling 220 mg/m2 or more
• LVEF less than 45%
• Patients with >grade II sensory neuropathy at baseline as assessed by the PI will be excluded
• No history of seizures as ALCAR may lower the seizure threshold
• Known HIV infection
• Current pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bort, Dex, and Dox with ALCAR	Drug: Bort, Dex, and Dox with ALCAR; Bortezomib 1.3 mg/m2 IV days 1, 4, 8, and 11 Dexamethasone 20 mg PO days 1, 4, 8, and 11 Doxorubicin 15 mg/m2 IV days 1 and 8 Acetyl-L-Carnitine (ALCAR) 1.5 g PO BID days 1-21 Maximum of 8 cycles. Each cycle is 21 days long; Other Names: Velcade, cc-5013, ALCAR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed Anti-tumor Response Rate (Complete Response and Partial Response) to the Combination of Bortezomib, Dexamethasone, Doxorubicin, and ALCAR	Anti-tumor responses were analyzed descriptively and summarized in tabular format. Ninety percent confidence intervals for the percentage of subjects with a confirmed anti-tumor response were constructed using the method proposed by Duffy-Santner. Complete response defined as: no evidence of M-protein on immunofixation of serum and/or urine AND less than 5% plasma cells in the bone marrow biopsy. Partial response defined as: 50 to 99% decrease in M-protein on serum and/or urine protein electrophoresis.	Every 21 days, up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival		From date of randomization until the date of death from any cause, assessed up to 7 years
Progression-free Survival	Progression is defined as any of the following: 1) 25% or greater increase in M-protein as measured by serum or urine protein electrophoresis. There must be an absolute minimum increase of 0.5 g/dl in serum M spike or 0.2 gram of specific urinary light chains to constitute progression, 2) 25% or greater increase in the percentage or plasma cells in the bone marrow biopsy, or 3) new bone lesions or an increase in the size of old lesions on x-ray.	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 7 years.

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: Millennium Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Natalie S Callander, MD, UWCCC

Study record dates

Study Major Dates

• Study Start: February 1, 2004
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: December 19, 2007
• First Submitted That Met QC Criteria: December 27, 2007
• First Posted (Estimate): December 28, 2007

Study Record Updates

• Last Update Posted (Actual): December 13, 2019
• Last Update Submitted That Met QC Criteria: December 11, 2019
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: previously treated multiple myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Nootropic Agents; Acetylcarnitine
• Other Study ID Numbers: HO04402; A534260 (Other Identifier: UW Madison); SMPH\MEDICINE\HEM-ONC (Other Identifier: UW Madison); H-2004-0064 (Other Identifier: Institutional Review Board); NCI-2011-00516 (Registry Identifier: NCI Trial ID)