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A Study to Evaluate the Use of Chloroquine in Combination With VELCADE and Cyclophosphamide in Patients With Relapsed and Refractory Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT01438177
First received: September 8, 2011
Last updated: June 16, 2014
Last verified: June 2014
  Purpose

Patients with myeloma that has either not responded to previous treatment or has returned after previous treatment will be given a combination of the drugs chloroquine, cyclophosphamide and bortezomib.

VELCADE will be given intravenously on days 1, 4, 8, 11, 22, 25, 29 and 32. Cyclophosphamide will be given orally 2x/day and Chloroquine orally daily both on days 1-14 and 22-35. 14 patients will be treated with this regimen. Each cycle will be 42 days in length. Patients will receive the study drugs until their disease progresses or they are withdrawn from the study.

In other studies, Velcade seems to work well with other drugs. Thus, this study hopes to show that the combination of Cyclophosphamide and Chloroquine, will have activity in relapsed/refractory myeloma.


Condition Intervention Phase
Multiple Myeloma
Drug: Cyclophosphamide
Drug: Velcade
Drug: Chloroquine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, Trial of Chloroquine in Combination With VELCADE and Cyclophosphamide in Patients With Relapsed and Refractory Myeloma

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • Response rate (CR + PR after 2 cycles) [ Time Frame: after 84 days ] [ Designated as safety issue: No ]
    each cycle is 42 days long


Secondary Outcome Measures:
  • Number of participants with adverse events of grade 3 or higher (based on CTCAE 4.0 scale) [ Time Frame: days 1, 4, 8, 11, 15, 22, 25, 29, 32, 36 of each 42 day cycle ] [ Designated as safety issue: Yes ]
    toxicity will be assessed and graded by severity on these specified days, as the patient will come to clinic on these days. However, patients may contact the clinic any day to report any experienced toxicities and speak with a healthcare professional.

  • Percentage of subjects who have complete response or partial response and have 2+ or higher autophagy [ Time Frame: until clinical response (up to 2 years) ] [ Designated as safety issue: No ]
  • Duration of response of this regimen [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
    time from response until progression of disease/relapse


Enrollment: 11
Study Start Date: October 2011
Estimated Study Completion Date: December 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
Chloroquine, Velcade and Cyclophosphamide
Drug: Cyclophosphamide
Cyclophosphamide will be given at 50 mg orally twice per day daily, on days 1-14 and 22-35, the latter for the first cohort of 3 patients.
Other Names:
  • Endoxan
  • Cytoxan
  • Neosar
  • Procytox
  • Revimmune
Drug: Velcade
VELCADE will be given by intravenous push at 1.3 mg/m2 on days 1, 4, 8, 11, 22, 25, 29 and 32.
Other Names:
  • Bendamustine HCl
  • Treanda
Drug: Chloroquine
Chloroquine at 500 mg orally daily on days 1-14 and 21-35, the latter for the first cohort of 3 patients. If this dose of Chloroquine is tolerated, subsequent patients will receive Chloroquine at 500 mg twice a day on days 1-14 and 22-35.
Other Name: Aralen

Detailed Description:

The Purpose of this study is to test the safety of a combination of three anticancer medicines, called Chloroquine, Velcade and Cyclophosphamide. The cyclophosphamide will be used orally at doses that synergize with both VELCADE and chloroquine. The bid dose is chosen for cyclophosphamide to enable continuous exposure in this regard.

Here, the investigators propose to examine the hypothesis that combined exposure to Cyclophosphamide, VELCADE and Chloroquine will synergistically promote endoplasmic reticulum stress in multiple myeloma and thus synergistically lead to an antitumor effect measurable clinically.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. 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.
  3. 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

    1. Bone marrow plasmacytosis (10 to 30% plasma cells)
    2. Monoclonal immunoglobulin present but of lesser magnitude than given under major criteria
    3. Lytic bone lesions
    4. 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
    • Major criterion III plus minor criterion a or c
    • Minor criteria a, b and c or a, b and d
  4. Measurable disease, defined as a monoclonal immunoglobulin spike on serum electrophoresis of ≥ 1 Gm/dL and/or urine monoclonal immunoglobulin spike of ≥ 200 mg/24 hours.
  5. Patients must have refractory myeloma as defined by a greater than 25% increase in their M-protein. They should have progressed on a combination of VELCADE and cyclophosphamide.
  6. Non-secretors must have measurable protein by Freelite or measurable disease such as plasmacytoma to be eligible.
  7. Karnofsky performance status ≥ 50
  8. Patients treated with local radiotherapy with or without a brief exposure to steroids are eligible. Patients who require concurrent radiotherapy should have entry to the protocol deferred until the radiotherapy is completed
  9. Meets the following pretreatment laboratory criteria at Baseline (Day 1 of Cycle 1, before study drug administration)

    • Absolute neutrophil count ≥ 0.5 x 10^3/uL
    • Calculated or measured creatinine clearance ≥ 30 mL/min
  10. Age 18 years or older

Exclusion Criteria:

  1. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes)
  2. Plasma cell leukemia
  3. Receiving steroids daily for other medical conditions, e.g., asthma, systemic lupus erythematosis, rheumatoid arthritis
  4. Infection not controlled by antibiotics
  5. HIV infection. Patients should provide consent for HIV testing according to the institution's standard practice
  6. Known active hepatitis B or C
  7. 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.
  8. 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.
  9. 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.
  10. Other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol
  11. 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.
  12. Patient has > Grade 2 peripheral neuropathy
  13. Patient has known hypersensitivity to VELCADE, boron or mannitol, quinidine or quinidine derivatives or to cyclophosphamide or any component of the formulation.
  14. 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.
  15. Patients with preexisting retinal or visual field changes.
  16. Patient has > 1.5 x ULN Total Bilirubin
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01438177

Locations
United States, New York
NYU Cancer Institute
New York, New York, United States, 10016
Sponsors and Collaborators
New York University School of Medicine
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Amitabha Mazumder, MD NYU Langone Medical Center
  More Information

No publications provided

Responsible Party: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT01438177     History of Changes
Other Study ID Numbers: NYU# 10-02008
Study First Received: September 8, 2011
Last Updated: June 16, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by New York University School of Medicine:
myeloma
multiple myeloma
relapsed myeloma
refractory myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Bortezomib
Chloroquine
Chloroquine diphosphate
Cyclophosphamide
Alkylating Agents
Amebicides
Analgesics
Analgesics, Non-Narcotic
Anthelmintics
Anti-Infective Agents
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antimalarials
Antinematodal Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on November 20, 2014