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Trial record 50 of 2596 for:    "Plasma Cell Neoplasm"

Hydroxychloroquine and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT00568880
Recruitment Status : Completed
First Posted : December 6, 2007
Last Update Posted : April 16, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Abramson Cancer Center of the University of Pennsylvania

Tracking Information
First Submitted Date  ICMJE December 5, 2007
First Posted Date  ICMJE December 6, 2007
Last Update Posted Date April 16, 2019
Actual Study Start Date  ICMJE September 8, 2010
Actual Primary Completion Date April 2, 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 12, 2019)
  • Dose-limiting toxicity [ Time Frame: 8 weeks or if subject continues to improve subject may continue treatment. ]
  • Maximum tolerated dose of hydroxychloroquine [ Time Frame: 8 weeks or if subject continues to improve subject may continue treatment.] ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 5, 2007)
  • Dose-limiting toxicity
  • Maximum tolerated dose of hydroxychloroquine
Change History Complete list of historical versions of study NCT00568880 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 12, 2019)
  • Myeloma response (stringent complete response [sCR], CR, very good partial response [VGPR], PR, stable disease, and progressive disease) [ Time Frame: 8 weeks or if subject continues to improve subject may continue treatment. ]
  • Overall survival [ Time Frame: 8 weeks or if subject continues to improve subject may continue treatment. ]
  • Time to treatment failure [ Time Frame: 8 weeks or if subject continues to improve subject may continue treatment. ]
  • Progression-free survival [ Time Frame: 8 weeks or if subject continues to improve subject may continue treatment. ]
  • Time to response [ Time Frame: 8 weeks or if subject continues to improve subject may continue treatment. ]
  • Duration of overall response [ Time Frame: 8 weeks or if subject continues to improve subject may continue treatment. ]
  • Correlation of hydroxychloroquine and its metabolites blood levels with efficacy by mass spectrometry [ Time Frame: 8 weeks or if subject continues to improve subject may continue treatment. ]
  • Pre- and post-bortezomib proteasome inhibition assays [ Time Frame: 8 weeks or if subject continues to improve subject may continue treatment. ]
  • Bone marrow aspirate and peripheral blood mononuclear cell analysis for aggresome formation, autophagy inhibition, and apoptosis [ Time Frame: 8 weeks or if subject continues to improve subject may continue treatment. ]
  • Rate of overall adverse events and serious adverse events [ Time Frame: 8 weeks or if subject continues to improve subject may continue treatment. ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 5, 2007)
  • Myeloma response (stringent complete response [sCR], CR, very good partial response [VGPR], PR, stable disease, and progressive disease)
  • Overall survival
  • Time to treatment failure
  • Progression-free survival
  • Time to response
  • Duration of overall response
  • Correlation of hydroxychloroquine and its metabolites blood levels with efficacy by mass spectrometry
  • Pre- and post-bortezomib proteasome inhibition assays
  • Bone marrow aspirate and peripheral blood mononuclear cell analysis for aggresome formation, autophagy inhibition, and apoptosis
  • Rate of overall adverse events and serious adverse events
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hydroxychloroquine and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma
Official Title  ICMJE A Phase I/II Trial of Hydroxychloroquine Added to Bortezomib for Relapsed/Refractory Myeloma
Brief Summary

RATIONALE: Drugs used in chemotherapy, such as hydroxychloroquine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving hydroxychloroquine together with bortezomib may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of hydroxychloroquine when given together with bortezomib and to see how well it works in treating patients with relapsed or refractory multiple myeloma.

Detailed Description

OBJECTIVES:

Primary

  • To establish the dose-limiting toxicities and maximum tolerated dose of hydroxychloroquine when added to a standard-dose regimen of bortezomib for treatment of patients with relapsed or refractory multiple myeloma.

Secondary

  • To obtain a preliminary estimate of the toxicity rate and response rate of this combination at the maximum tolerated dose.
  • To confirm preclinical evidence showing synergistic effects of hydroxychloroquine and bortezomib by correlating response rate with blood levels of hydroxychloroquine and degree of autophagy inhibition in repeated bone marrow samples.

OUTLINE: This is a phase I dose-escalation study of hydroxychloroquine followed by a phase II study.

  • Phase I: Patients receive oral hydroxychloroquine every other day for 2 weeks. Patients then receive oral hydroxychloroquine 1-3 times daily or every other day and bortezomib IV twice a week for 2 weeks. Treatment with hydroxychloroquine and bortezomib repeats every 3 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. Once the maximum tolerated dose (MTD) for hydroxychloroquine is determined, additional patients are accrued to the phase II portion of the study.
  • Phase II: Patients receive hydroxychloroquine (at the MTD determined in phase I) and bortezomib as in phase I.

Blood and bone marrow samples are collected periodically during the study for correlative studies by mass spectrometry, proteasome inhibition assays, pharmacokinetic analysis and assessment of aggresome formation, autophagy inhibition, and apoptosis by protein electrophoresis and serum free light-chain analysis.

After completion of study treatment, patients are followed periodically.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma and Plasma Cell Neoplasm
Intervention  ICMJE
  • Drug: bortezomib
  • Drug: hydroxychloroquine
  • Other: immunologic technique
  • Other: laboratory biomarker analysis
  • Other: mass spectrometry
  • Other: pharmacological study
  • Procedure: biopsy
Study Arms  ICMJE Experimental: Hydroxychloroquine Added to Bortezomib
Hydroxychloroquine will be given as a oral dose of 200 mg every other day - 1200mg daily (dose escalated by cohorts) Bortezomib will be given on days 1, 4, 8, and 11 of each 21 day cycle at doses of 1.0-1.3mg/m2 (dose escalated by cohorts)
Interventions:
  • Drug: bortezomib
  • Drug: hydroxychloroquine
  • Other: immunologic technique
  • Other: laboratory biomarker analysis
  • Other: mass spectrometry
  • Other: pharmacological study
  • Procedure: biopsy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 12, 2019)
25
Original Enrollment  ICMJE
 (submitted: December 5, 2007)
50
Actual Study Completion Date  ICMJE April 2, 2012
Actual Primary Completion Date April 2, 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Histologically confirmed multiple myeloma
  • Must meet 1 of the following criteria:

    • Relapsed disease documented
    • Disease refractory to at least one prior treatment regimen (may include autologous and allogeneic bone marrow transplantation)
    • In need of further therapy for myeloma, as determined by the patient's treating physician
  • No known CNS involvement

    • Calvarial lytic lesions or plasmacytomas are not exclusion criteria if there is no CNS involvement

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy ≥ 3 months
  • Absolute neutrophil count ≥ 500/μL
  • Hemoglobin ≥ 7 g/dL (with or without transfusion support)
  • Platelets ≥ 25,000/μL (with or without transfusion support)
  • Total bilirubin ≤ 2 x upper limit of normal (ULN)
  • AST/ALT ≤ 2.5 x ULN
  • Creatinine ≤ 2 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception prior to and during study treatment
  • No baseline peripheral neuropathy ≥ grade 2
  • No history of allergic reactions to compounds of similar chemical or biological composition to bortezomib or hydroxychloroquine
  • No known macular degeneration or retinopathy (diabetic or otherwise), porphyria, or psoriasis

    • Well-controlled psoriasis allowed provided under the care of a specialist who agrees to monitor the patient for exacerbations
  • No other conditions that would require therapy with hydroxychloroquine, including but not limited to, any of the following:

    • Systemic lupus
    • Rheumatoid arthritis
    • Porphyria cutanea tarda
    • Malaria treatment or prophylaxis
  • No concurrent or prior malignancy except for the following:

    • Basal cell or squamous cell carcinoma of the skin
    • Treated carcinoma in situ
    • Localized prostate adenocarcinoma (stage T1a or T1b) with a stable PSA for a period of at least 4 months allowed
    • Patients with a prior malignancy treated with chemotherapy, biologic agents, and/or radiation are eligible for this study if they have completed therapy ≥ 4 years previously with no evidence of recurrent disease
    • Patients with a prior malignancy treated with surgery alone are eligible for this study if they have completed therapy ≥ 2 years previously with no evidence of recurrent disease
  • No uncontrolled intercurrent illness including, but not limited to, any of the following:

    • Uncontrolled ongoing infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness or social situations that would limit compliance with study requirements
  • No prior dose-limiting toxicity due to bortezomib administration
  • No inability to understand or unwillingness to sign the informed consent document

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 7 days since prior corticosteroids
  • At least 14 days since prior antimyeloma agents, including thalidomide or lenalidomide
  • Concurrent therapy with bisphosphonates allowed at the discretion of the treating physician
  • Concurrent hematopoietic growth factors allowed, including filgrastim (G-CSF) or pegfilgrastim, epoetin alpha, and darbepoetin alpha
  • Concurrent participation in non-treatment studies allowed, if it will not interfere with participation in this study
  • No concurrent radiotherapy except local radiotherapy during the treatment phase of this study for palliation of pain or prevention of fracture
  • No concurrent treatment with a different investigational regimen
  • No concurrent therapy with other anticancer agents
  • No concurrent participation in other investigational trials that involve novel therapies
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00568880
Other Study ID Numbers  ICMJE CDR0000577505
UPCC-01407
UPCC-IRB-806149
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Abramson Cancer Center of the University of Pennsylvania
Study Sponsor  ICMJE Abramson Cancer Center of the University of Pennsylvania
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Dan Vogl, MD Abramson Cancer Center of the University of Pennsylvania
PRS Account Abramson Cancer Center of the University of Pennsylvania
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP