Study of Oral IXAZOMIB in Combination With Melphalan and Prednisone in Patients With Newly Diagnosed Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Millennium Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01335685
First received: April 8, 2011
Last updated: May 23, 2014
Last verified: May 2014

April 8, 2011
May 23, 2014
June 2011
January 2016   (final data collection date for primary outcome measure)
  • Maximum Tolerated Dose and Recommended phase 2 dose of IXAZOMIB (phase 1) [ Time Frame: Dose Limiting Toxicities determined in Cycle 1 and adverse events monitored throughout the study will inform the recommended phase 2 dose, approximately 2 years ] [ Designated as safety issue: Yes ]
    Based on toxicity and efficacy outcomes
  • Number of patients with a complete response and very good partial response (phase 2) [ Time Frame: During the induction period, approximately 1 year ] [ Designated as safety issue: No ]
    Combined response rate
  • Maximum Tolerated Dose and Recommended phase 2 dose of MLN9708 (phase 1) [ Time Frame: Dose Limiting Toxcities determined in Cycle 1 and adverse events monitored throughout the study will inform the recommended phase 2 dose, approximately 2 years ] [ Designated as safety issue: Yes ]
    Based on toxicity and efficacy outcomes
  • Number of patients with a complete response and very good partial response (phase 2) [ Time Frame: During the induction period, approximately 1 year ] [ Designated as safety issue: No ]
    Combined response rate
Complete list of historical versions of study NCT01335685 on ClinicalTrials.gov Archive Site
  • Maximum inhibition (Emax) and time of occurrence of Emax (TEmax) (phase 1) [ Time Frame: At multiple time points during cycles 1-3 of each phase and arm of the study, throughout approximately 84-126 days depending on the arm of the study ] [ Designated as safety issue: No ]
    Whole blood 20S proteasome inhibition parameters
  • Maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), and area under the plasma concentration-time curve (AUC) (phase 1) [ Time Frame: At multiple time points during cycles 1-3 of each phase and arm of the study, throughout approximately 84-126 days depending on the arm of the study ] [ Designated as safety issue: No ]
    Single and multiple dose plasma pharmacokinetics
  • Number of patients with response, including Complete Response, Very Good Partial Response and Partial Response (phase 1 and 2) [ Time Frame: Duration of treatment and then every 12 weeks thereafter until disease progression or initiation of subsequent antineoplastic therapy, expected duration approximately 4 years ] [ Designated as safety issue: No ]
    Overall reponse rate
  • Time to response (phase 2) [ Time Frame: From the date of enrollment to the date of the first documented response during the induction period, expected average of up to 1 year ] [ Designated as safety issue: No ]
  • Duration of response (phase 2) [ Time Frame: From the date of first response to the date of disease progression, approximately 4 years ] [ Designated as safety issue: No ]
  • Time to progression (phase 2) [ Time Frame: From date of enrollment to the date of first documented disease progression, approximately 4 years ] [ Designated as safety issue: No ]
  • Time to next therapy (phase 2) [ Time Frame: From the date of enrollment to the date of subsequent antineoplastic therapy, approximately 4 years ] [ Designated as safety issue: No ]
  • Number of patients with progression free survival (phase 2) [ Time Frame: From the date of enrollment to the date of first documented disease progression or death, approximately 4 years ] [ Designated as safety issue: No ]
  • Number of patients with overall survival (phase 2) [ Time Frame: From date of enrollment to date of death, approximately 4 years ] [ Designated as safety issue: No ]
  • Number of all adverse events (phase 2) [ Time Frame: From first dose of study drug through 30 days after last dose of study drug or until the start of subsequent antineoplastic therapy, approximately 2 years and 30 days ] [ Designated as safety issue: Yes ]
  • Assessments of Quality of Life (phase 2) [ Time Frame: At screening, Day 1 of each treatment cycle, and Days 1 and 15 of each maintenance cycle, approximately 2 years ] [ Designated as safety issue: No ]
  • Maximum inhibition (Emax) and time of occurrence of Emax (TEmax) (phase 1) [ Time Frame: At mulitple time points during cycles 1-3 of each phase and arm of the study, throughout approximately 84-126 days depending on the arm of the study ] [ Designated as safety issue: No ]
    Whole blood 20S proteasome inhibition parameters
  • Maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), and area under the plasma concentration-time curve (AUC) (phase 1) [ Time Frame: At mulitple time points during cycles 1-3 of each phase and arm of the study, throughout approximately 84-126 daus depending on the arm of the study ] [ Designated as safety issue: No ]
    Single and multiple dose plasma pharmacokinetics
  • Number of patients with response, including Complete Response, Very Good Partial Response and Partial Response (phase 1 and 2) [ Time Frame: Duration of treatment and then every 12 weeks thereafter until disease progression or initiation of subsequent antineoplastic therapy, expected duration approximately 4 years ] [ Designated as safety issue: No ]
    Overall reponse rate
  • Time to response (phase 2) [ Time Frame: From the date of enrollment to the date of the first documented response during the induction period, expected average of up tp 1 year ] [ Designated as safety issue: No ]
  • Duration of response (phase 2) [ Time Frame: From the date of first response to the date of disease progression, approximately 4 years ] [ Designated as safety issue: No ]
  • Time to progression (phase 2) [ Time Frame: From date of enrollment to the date of first documented disease progression, approximately 4 years ] [ Designated as safety issue: No ]
  • Time to next therapy (phase 2) [ Time Frame: From the date of enrollment to the date of subsequent antineoplastic therapy, approximately 4 years ] [ Designated as safety issue: No ]
  • Number of patients with progression free survival (phase 2) [ Time Frame: From the date of enrollment to the date of first documented disease progression or death, approximately 4 years ] [ Designated as safety issue: No ]
  • Number of patients with overall survival (phase 2) [ Time Frame: From date of enrollment to date of death, approximately 4 years ] [ Designated as safety issue: No ]
  • Number of all adverse events (phase 2) [ Time Frame: From first dose of study drug through 30 days after last dose of study drug or until the start of subsequent antineoplastic therapy, approximately 2 years and 30 days ] [ Designated as safety issue: Yes ]
  • Assessments of Quality of Life (phase 2) [ Time Frame: At screening, Day 1 of each treatment cycle, and Days 1 and 15 of each maintenance cycle, approximately 2 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Study of Oral IXAZOMIB in Combination With Melphalan and Prednisone in Patients With Newly Diagnosed Multiple Myeloma
An Open-Label, Dose-Escalation, Phase 1/2 Study of the Oral Form of IXAZOMIB (MLN9708), a Next-Generation Proteasome Inhibitor, Administered in Combination With a Standard Care Regimen of Melphalan and Prednisone in Patients With Newly Diagnosed Multiple Myeloma Requiring Systemic Treatment

This will be a phase 1/2, multicenter, 2-arm, open-label study using the oral formulation of IXAZOMIB when added to standard melphalan and prednisone (MP) treatment. Both phases of the study will include patients who have newly diagnosed multiple myeloma and are ineligible for high-dose therapy plus stem cell transplantation because of age (≥65 years of age) or coexisting conditions and for whom standard MP treatment is indicated.

Note: Phase 2 of the trial will be randomized.

Not Provided
Interventional
Phase 1
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Multiple Myeloma
  • Drug: IXAZOMIB
  • Drug: Melphalan 9 mg/m2
  • Drug: Melphalan 6 mg/m2
  • Drug: Prednisone
    60 mg/m2
  • Experimental: Twice Weekly, 6-week cycle

    Phase 1 only.

    Induction:

    IXAZOMIB on days 1, 4, 8, 11, 22, 25, 29, 32. Melphalan 9 mg/m2 and Prednisone on days 1-4.

    Repeat every 42 days for 9 cycles.

    Maintenance:

    IXAZOMIB only on days 1, 8, 15 in 28-day cycle.

    Interventions:
    • Drug: IXAZOMIB
    • Drug: Melphalan 9 mg/m2
    • Drug: Prednisone
  • Experimental: Once Weekly, 4-week cycle

    Phases 1 and 2.

    Induction:

    IXAZOMIB on days 1, 8, 15. Melphalan 6 mg/m2 and Prednisone on days 1-4. Repeat every 28 days for 13 cycles.

    Maintenance:

    IXAZOMIB only on days 1, 8, 15 in 28-day cycle.

    Interventions:
    • Drug: IXAZOMIB
    • Drug: Melphalan 6 mg/m2
    • Drug: Prednisone
  • Experimental: Once Weekly, 6-week cycle (5weeks on/1 week off)

    Phases 1 and 2

    Induction:

    IXAZOMIB on days 1, 8, 15, 22, 29. Melphalan 9 mg/m2 and Prednisone on days 1-4. Repeat every 42 days for 9 cycles.

    Maintenance:

    IXAZOMIB only on days 1, 8, 15 in 28-day cycle.

    Phase 2 will include either Arm C or Arm D based on the safety, tolerability and efficacy observed in Phase 1.

    Interventions:
    • Drug: IXAZOMIB
    • Drug: Melphalan 9 mg/m2
    • Drug: Prednisone
  • Experimental: Once Weekly, 6-week cycle (2 weeks on/ 1 week off)

    Phases 1 and 2

    Induction:

    IXAZOMIB on days 1, 8, 22, 29. Melphalan 9 mg/m2 and Prednisone on days 1-4. Repeat every 42 days for 9 cycles.

    Maintenance:

    IXAZOMIB only on days 1, 8, 15 in 28-day cycle.

    Phase 2 will include either Arm C or Arm D based on the safety, tolerability and efficacy observed in Phase 1.

    Interventions:
    • Drug: IXAZOMIB
    • Drug: Melphalan 9 mg/m2
    • Drug: Prednisone
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
164
March 2016
January 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male or female patient for whom standard melphalan prednisone (MP) treatment is indicated and who is not a candidate for high-dose therapy plus stem cell transplantation (HDT-SCT) for 1 of the following reasons: the patient is 65 years of age or older OR the patient is less than 65 years of age but has significant comorbid condition(s) that are likely to have a negative impact on tolerability of HDT-SCT
  • Symptomatic multiple myeloma or asymptomatic myeloma with myeloma-related organ damage diagnosed according to standard criteria
  • Measurable disease as specified in study protocol
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  • Must have adequate hematologic, liver, and renal function
  • Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to abstain from heterosexual intercourse
  • Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse
  • Voluntary written consent

Exclusion Criteria

  • Peripheral neuropathy that is greater or equal to Grade 2
  • Female patients who are lactating or pregnant
  • Major surgery or radiotherapy within 14 days before the first dose of study drug
  • Uncontrolled infection requiring systematic antibiotics
  • Diarrhea (> Grade 1)
  • Prior systemic therapy for multiple myeloma, including investigational drugs (prior treatment with corticosteroids or localized radiation therapy dose not disqualify the patient)
  • Central nervous system involvement
  • Cardiac status as described in protocol
  • Known gastrointestinal condition or procedure that could interfere with swallowing or the oral absorption of tolerance of IXAZOMIB - Diagnosis of smoldering multiple myeloma, Waldenstrom's macroglobulinemia, POEMS syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome
  • Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
  • Diagnosed or treated for another malignancy within 2 years before the first dose or previously diagnosed with another malignancy and have any evidence of residual disease with the exception of nonmelanoma skin cancer or any completely resected carcinoma in situ
  • Serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol
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,   Canada,   Czech Republic,   Italy,   Russian Federation,   Spain,   United Kingdom
 
NCT01335685
C16006, 2010-023772-71
No
Millennium Pharmaceuticals, Inc.
Millennium Pharmaceuticals, Inc.
Not Provided
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
Millennium Pharmaceuticals, Inc.
May 2014

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