Trial record 1 of 27 for:    C16011
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Study of Dexamethasone Plus IXAZOMIB or Physician's Choice of Treatment in Relapsed or Refractory Systemic Light Chain (AL) Amyloidosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Millennium Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01659658
First received: August 2, 2012
Last updated: June 23, 2014
Last verified: June 2014

August 2, 2012
June 23, 2014
December 2012
May 2018   (final data collection date for primary outcome measure)
  • Number of patients with overall hematologic response [ Time Frame: Assessed every 4 weeks (median length of the endpoint assessment period is projected to be approximately 36 months) ] [ Designated as safety issue: No ]
    Complete response, very good partial response and partial response
  • 2-year vital organ deterioration and mortality rate [ Time Frame: Monthly for up to 2 years or until death ] [ Designated as safety issue: No ]
    Rate of hospitalization for congestive heart failure or progression to end stage renal disease or death at 2 years
Same as current
Complete list of historical versions of study NCT01659658 on ClinicalTrials.gov Archive Site
  • Number of patients with complete hematologic response [ Time Frame: Assessed every 4 weeks (median length of the endpoint assessment period is projected to be approximately 36 months) ] [ Designated as safety issue: No ]
    Overall complete hematologic response
  • Overall survival [ Time Frame: Monthly up to 5 years ] [ Designated as safety issue: No ]
    Time from randomization to the date of death
  • Progression free survival [ Time Frame: Monthly up to 5 years ] [ Designated as safety issue: No ]
    Time from date of randomization to the date of first documentation of disease progression or death, whichever occurs first
  • Hematologic disease progression free survival [ Time Frame: Monthly up to 5 years ] [ Designated as safety issue: No ]
    Time from the date of randomization to the date of first documented hematologic disease progression or death, whichever occurs first
  • Time to vital organ deterioration and mortality rate [ Time Frame: Monthly up to 5 years ] [ Designated as safety issue: No ]
    Time from date of randomization to the first date of either death or hospitalization for congestive heart failure or progression to endstage renal disease
  • Number of patients with cardiac and/or kidney response [ Time Frame: Every 3 cycles until disease progression ] [ Designated as safety issue: No ]
    Overall organ response rate
  • Vital organ progression free survival [ Time Frame: Every 3 cycles until disease progression ] [ Designated as safety issue: No ]
    Time from the date of randomization to the date of first documentation of progression of vital organ, or death, whichever occurs first
  • Duration of hematologic response [ Time Frame: Monthly up to 5 years ] [ Designated as safety issue: No ]
    Time from the date of first documentation of hematologic response to the date of first documented hematologic disease progression
  • Number of adverse events [ Time Frame: Monthly up to 5 years ] [ Designated as safety issue: Yes ]
    Adverse events, serious adverse events, assessment of clinical laboratory values from the date of signing of the informed consent form through 30 days after the last dose of study drug.
  • Time to treatment failure [ Time Frame: Monthly up to 5 years ] [ Designated as safety issue: No ]
    Time from date of randomization to the date of first documented treatment failure
  • Time to subsequent anticancer treatment [ Time Frame: Monthly up to 5 years ] [ Designated as safety issue: No ]
    Time from date of randomization to the start date of subsequent anticancer treatment
  • Results of Quality of Life Assessment [ Time Frame: At screening; Cycle 1, Day 1; Cycle 2, Day 1; Cycle 3, Day 1; Day 1 of every 3 cycles until disease progression ] [ Designated as safety issue: No ]
  • Number of medical encounters patient experiences [ Time Frame: At screening; Cycle 1, Day 1; Cycle 2, Day 1; Cycle 3, Day 1; Day 1 of every 3 cycles until disease progression ] [ Designated as safety issue: No ]
    Number of admissions to an inpatient and outpatient setting for any reason (including length of stay, inpatient, outpatient, reason, number of missing days from work or other activities by patient or care-giver and EQ-5D scores questionnaire data
  • Time to reach plasma concentration [ Time Frame: Cycle 1, Days 1 and 14; Cycle 2, Days 1 and 14; Cycles 3-10, Day 1 ] [ Designated as safety issue: No ]
    Pharmacokinetics
  • Investigate the association of clinical outcomes and polymorphic genes [ Time Frame: At screening ] [ Designated as safety issue: No ]
    Analysis of relevant signaling pathway genes in whole blood samples
Same as current
Not Provided
Not Provided
 
Study of Dexamethasone Plus IXAZOMIB or Physician's Choice of Treatment in Relapsed or Refractory Systemic Light Chain (AL) Amyloidosis
A Phase 3, Randomized, Controlled, Open-label, Multicenter, Safety and Efficacy Study of Dexamethasone Plus IXAZOMIB (MLN9708) or Physician's Choice of Treatment Administered to Patients With Relapsed or Refractory Systemic Light Chain (AL) Amyloidosis

This is a phase 3, randomized, controlled, open-label, multicenter study of the oral formulation of dexamethasone plus IXAZOMIB compared with treatment chosen by the investigator from a prespecified list of regimens available in clinical practice. Treatment options will include: dexamethasone alone, dexamethasone plus an alkylating agent (melphalan or cyclophosphamide), or dexamethasone plus an immunomodulatory drug (IMiD, thalidomide or lenalidomide) in patients with relapsed or refractory AL amyloidosis. Crossover to the investigational treatment arm is not permitted during participation in this study.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Relapsed or Refractory Systemic Light Chain Amyloidosis
  • Drug: IXAZOMIB
  • Drug: Dexamethasone
  • Drug: Melphalan
  • Drug: Cyclophosphamide
  • Drug: Thalidomide
  • Drug: Lenalidomide
  • Experimental: IXAZOMIB plus Dexamethasone
    Patients will receive IXAZOMIB (4.0 mg) orally (PO) on Days 1, 8, and 15 plus dexamethasone 20 mg/day PO weekly on Days 1, 8, 15, and 22 of each 28-day cycle; dexamethasone may be increased up to 40 mg/day after 4 weeks, if tolerated. Patients may continue to receive treatment until PD or unacceptable toxicity, whichever comes first.
    Interventions:
    • Drug: IXAZOMIB
    • Drug: Dexamethasone
  • Active Comparator: Physician's Choice

    Patients will receive one of the following treatment options as selected by the physician:

    • Dexamethasone: 20 mg/day orally (PO) on Days 1-4, 9-12 & 17- 20 of each 28-day cycle
    • Dexamethasone + melphalan: Dexamethasone 20 mg/day PO on Days 1-4 of each 28-day; plus melphalan 0.22 mg/kg PO on Days 1-4 every 28 days.
    • Dexamethasone + cyclophosphamide: Dexamethasone 20 mg/day PO weekly on Days 1, 8, 15 & 22 of each 28-day cycle; plus cyclophosphamide 500 mg PO Days 1, 8 & 15 every 28 days.
    • Dexamethasone + thalidomide: Dexamethasone 20 mg/day PO weekly Days 1, 8, 15 & 22 of each 28-day cycle; plus thalidomide total dose up to 200 mg/day PO
    • Dexamethasone + lenalidomide: Dexamethasone 20 mg/day PO weekly on Days 1, 8, 15 & 22 of each 28-day cycle; plus lenalidomide 15 mg/day for 21 days every 28 days.

    In all treatments dexamethasone may be increased up to 40 mg/day after 4 weeks, if the lower dose is tolerated without any > Grade 2 dexamethasone-related toxicities.

    Interventions:
    • Drug: Dexamethasone
    • Drug: Melphalan
    • Drug: Cyclophosphamide
    • Drug: Thalidomide
    • Drug: Lenalidomide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
248
August 2018
May 2018   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male or female patients 18 years or older
  • Biopsy-proven AL amyloidosis with relapsed or refractory disease despite 1 or 2 prior therapies. Patients may be proteasome inhibitor-exposed or naive, but cannot be refractory to proteasome inhibitor therapy
  • Disease requiring further treatment
  • Measurable disease as defined by serum differential free light chain concentration (dFLC)
  • Objective and measurable major organ involvement (ie, cardiac or renal) as defined by the standard International Society of Amyloidosis (ISA) criteria.
  • Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2
  • Meet the clinical laboratories criteria as specified in the protocol
  • Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception through 90 days after the last dose of study treatment or agree to practice true abstinence; must also adhere to the guidelines of any treatment specific pregnancy prevention program
  • Male patients who agree to practice effective barrier contraception through 90 days after the last dose of study treatment or agree to practice true abstinence AND must adhere to the guidelines of any treatment specific pregnancy prevention program
  • Voluntary written consent

Exclusion Criteria:

  • Amyloidosis due to mutations of the transthyretin gene or presence of other non-AL amyloidosis
  • Female patients who are lactating, breastfeeding or pregnant
  • Evidence of current uncontrolled cardiovascular conditions as specified in study protocol
  • Clinically overt multiple myeloma as specified in study protocol
  • Inability to swallow medication, inability or unwillingness to comply with the drug administration requirements, or gastrointestinal (GI) procedure that could interfere with the oral absorption or tolerance of treatment
  • Requirement for other concomitant chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered to be investigational or which would be considered as a treatment of AL amyloidosis. However, patients may be on chronic steroids (maximum dose 20 mg/day prednisone or equivalent if they are being given for disorders other than amyloidosis
  • Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Ongoing or active infection, known HIV positive, active hepatitis B or C infection
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Known allergy to any of the study medications, their analogues or excipients
  • Systemic treatment with strong inhibitors of CYP1A2, strong inhibitors of CYP3A, or strong CYP3A inducers, or use of Ginkgo biloba or St. John's wort within 14 days before the first dose of study treatment
  • Diagnosed or treated for another malignancy within 5 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
Both
18 Years and older
No
Contact: For an updated listing of recruitment sites contact: Millennium Medical and Drug Information Center 1-877-674-3784 medical@mlnm.com
United States,   Australia,   Canada,   Denmark,   France,   Germany,   Greece,   Israel,   Italy,   Korea, Republic of,   Netherlands,   Spain,   United Kingdom
 
NCT01659658
C16011, 2011-005468-10
Yes
Millennium Pharmaceuticals, Inc.
Millennium Pharmaceuticals, Inc.
Not Provided
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
Millennium Pharmaceuticals, Inc.
June 2014

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