Chloroquine in Combination With VELCADE and Cyclophosphamide for Relapsed and Refractory Multiple Myeloma

NCT01438177 | Terminated Phase 2 Results DMC

• 1 other identifier: 10-02008
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot phase II trial studies how well giving bortezomib and cyclophosphamide together with chloroquine works in treating patients with relapsed or refractory multiple myeloma.

Conditions

Multiple Myeloma

Keywords

myeloma; multiple myeloma; relapsed myeloma; refractory myeloma

Outcome Measures

Primary Outcomes (1)

• Response Rate (CR + PR After 2 Cycles)

  Response rate is defined as the percentage of patients who have a complete response (CR) or partial response (PR). Responses were assessed every two cycles of treatment, based on the criteria published by the International Myeloma Working Group (Durie, et al, 2006). Per International Myeloma Working Group response criteria: CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow PR: \> 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by \>90% or to \< 200 mg/24 h

  Up to 2 years

Secondary Outcomes (3)

• Number of Participants With Adverse Events of Grade 3 or Higher

  Treatment period plus 30 days post-treatment

• Percentage of Subjects Who Have Complete Response or Partial Response and Have 2+ or Higher Autophagy

  until clinical response (up to 2 years)

• Median Duration of Response of This Regimen

  up to 2 years

Study Arms (1)

Velcade+Cyclophosphamide+Chloroquine

EXPERIMENTAL

VELCADE given by intravenous push at 1.3 mg/m\^2 on days 1, 4, 8, 11, 22, 25, 29 and 32. Cyclophosphamide given at 50 mg orally twice per day on days 1-14 and 22-35. Chloroquine given at 500 mg orally daily on days 1-14 and 22-35. Each cycle is 42 days in length.

Drug: Velcade; Drug: Cyclophosphamide; Drug: Chloroquine

Interventions

Velcade DRUG

Also known as: Bendamustine HCl, Treanda, Bortezomib

Velcade+Cyclophosphamide+Chloroquine

Cyclophosphamide DRUG

Also known as: Cytoxan, Neosar, Endoxan, Revimmune, Procytox

Velcade+Cyclophosphamide+Chloroquine

Chloroquine DRUG

Also known as: Aralen

Velcade+Cyclophosphamide+Chloroquine

Eligibility Criteria

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

You may qualify if:

• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• Female subject is either post-menopausal for at least 1 year before the screening visit, is surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of VELCADE, or agree to completely abstain from heterosexual intercourse. Male subjects, even if surgically sterilized (ie, status postvasectomy) must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse.
• Diagnosis of multiple myeloma based on standard criteria as follows:
• Major Criteria:
• I. Plasmacytomas on tissue biopsy
• II. Bone marrow plasmacytosis (\>30% plasma cells)
• III. Monoclonal immunoglobulin spike on serum electrophoresis (IgG \>3.5 G/dL or IgA \> 2.0 G/dL) or kappa or lambda light chain excretion\> 1 G/day on 24 hour urine protein electrophoresis
• Minor Criteria
• Bone marrow plasmacytosis (10 to 30% plasma cells)
• Monoclonal immunoglobulin present but of lesser magnitude than given under major criteria
• Lytic bone lesions
• Normal IgM \< 50 mg/dL, IgA \< 100 mg/dL, or IgG \< 600 mg/dL
• Any of the following sets of criteria will confirm the diagnosis of Multiple Myeloma:
• Any two of the major criteria
• Major criterion I plus minor criterion b, c, or d

You may not qualify if:

• POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes)
• Plasma cell leukemia
• Receiving steroids daily for other medical conditions, e.g., asthma, systemic lupus erythematosis, rheumatoid arthritis
• Infection not controlled by antibiotics
• HIV infection. Patients should provide consent for HIV testing according to the institution's standard practice
• Known active hepatitis B or C
• Patient had myocardial infarction within 6 months prior to enrollment, New York Hospital Association (NYHA) Class III or IV heart failure, (see appendix D), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
• Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
• Radiation therapy within 3 weeks before randomization. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy.
• Other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol
• Female subject is pregnant or lactating. Confirmation that the subject is not pregnant must be established by a negative serum B-human chorionic gonadotropin (B hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for postmenopausal or surgically sterilized women.
• Patient has \> Grade 2 peripheral neuropathy
• Patient has known hypersensitivity to VELCADE, boron or mannitol, quinidine or quinidine derivatives or to cyclophosphamide or any component of the formulation.
• Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial.
• Patients with preexisting retinal or visual field changes.

Sponsors & Collaborators

• NYU Langone Health: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

NYU Cancer Institute

New York, New York, 10016, United States

Location

Related Publications (1)

• Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K, Gertz M, Dimopoulos M, Westin J, Sonneveld P, Ludwig H, Gahrton G, Beksac M, Crowley J, Belch A, Boccadaro M, Cavo M, Turesson I, Joshua D, Vesole D, Kyle R, Alexanian R, Tricot G, Attal M, Merlini G, Powles R, Richardson P, Shimizu K, Tosi P, Morgan G, Rajkumar SV; International Myeloma Working Group. International uniform response criteria for multiple myeloma. Leukemia. 2006 Sep;20(9):1467-73. doi: 10.1038/sj.leu.2404284. Epub 2006 Jul 20.

  PMID: 16855634 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Bortezomib; Bendamustine Hydrochloride; Cyclophosphamide; Chloroquine

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; Butyrates; Acids, Acyclic; Carboxylic Acids; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phosphoramide Mustards; Phosphoramides; Organophosphorus Compounds; Aminoquinolines; Quinolines

Results Point of Contact

• Title: Amitabha Mazumder, MD
• Organization: Perlmutter Cancer Center

amitabha.mazumder@nyumc.org

212-731-5757

Study Officials

• Michael Grossbard, MD

  NYU Langone Medical 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: September 8, 2011
• First Posted: September 21, 2011
• Study Start: October 1, 2011
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: February 24, 2020
• Results First Posted: June 1, 2015

Record last verified: 2020-02

Locations

US (1)