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Study of Oral IXAZOMIB in Adult Patients With Relapsed or Refractory Light Chain Amyloidosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01318902
Recruitment Status : Active, not recruiting
First Posted : March 21, 2011
Last Update Posted : April 13, 2018
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Brief Summary:
This study will include patients with previously treated systemic relapsed or refractory light-chain (AL) amyloidosis who require further therapy and will be aimed at determining the safety profile and the maximum tolerated dose/recommended phase 2 dose of IXAZOMIB administered orally.

Condition or disease Intervention/treatment Phase
Light-Chain Amyloidosis Drug: MLN9708 Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Dose-Escalation, Phase 1 Study of the Oral Formulation of IXAZOMIB (MLN9708) Administered Weekly in Adult Patients With Relapsed or Refractory Light-Chain Amyloidosis Who Require Further Treatment
Actual Study Start Date : May 19, 2011
Actual Primary Completion Date : December 6, 2013
Estimated Study Completion Date : July 15, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Amyloidosis
U.S. FDA Resources

Arm Intervention/treatment
Experimental: MLN9708 Drug: MLN9708
Patients will receive escalating doses of MLN9708 orally on Days 1, 8 and 15 of a 28-day cycle. If there is no hematologic response after completion of 3 cycles, dexamethasone will be added on Days 1 to 4 of every cycle beginning with Cycle 4. If there is no hematologic response after the completion of 6 cycles, patients will discontinue therapy.

Primary Outcome Measures :
  1. Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: From start of study through 30 days after last dose or until initiation of subsequent antineoplastic therapy ]
  2. Maximum Tolerated Dose and Recommended phase 2 dose of MLN9708 [ Time Frame: Dose Limiting Toxcities determined in Cycle 1 and adverse events monitored throughout the study will inform the recommended phase 2 dose ]
    Based on toxicity and efficacy outcomes

Secondary Outcome Measures :
  1. Whole blood 20S proteasome activity profile and inhibition parameters of multiple-dose oral MLN9708 [ Time Frame: Days 1,2,8,15,16,22 ]
    Plasma pharmacokinetic and whole blood pharmacodynamic effect of MLN9708

  2. Number of patients with hematologic response rate during study period [ Time Frame: Duration of treatment and then every 6 weeks thereafter until disease progression or initiation of subsequent antineoplastic therapy ]
    Complete response, very good partial response, partial response

  3. Time to and duration of organ response and organ improvement [ Time Frame: After cycles 3,6,9,12; every 6 months thereafter until disease progression or initiation of subsequent antineoplastic therapy ]
    According to standardized criteria

  4. Time to hematologic and organ disease progression [ Time Frame: Until evidence of hematologic and/or disease progression ]
  5. Time from the date of the first dose of MLN9708 to the date of confirmed organ or hematologic disease progression, respectively [ Time Frame: Every 6 weeks from end of treatment until disease progression or initiation of subsequent antineoplastic therapy ]
    Progression free survival

  6. Patient survival probability at 1 year after the first dose of MLN9708 [ Time Frame: Every 12 weeks after progressive disease or initiation of subsequent antineoplastic therapy ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Male or female patients 18 years or older
  • Biopsy-proven systemic relapsed or refractory light-chain (AL) amyloidosis, which after at least 1 prior therapy, in the investigator's opinion, requires further treatment
  • If received stem cell transplant, must be at least 3 months posttransplantation and recovered from side effects
  • Must have measurable disease defined as serum differential free light chain concentration ≥ 40mg/L
  • Must have objective measurable organ (heart or kidney) amyloid involvement
  • Must have cardiac biomarker risk stage I or II disease
  • Must have adequate hematologic, hepatic, and renal function
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  • 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
  • Cardiac status as described in protocol
  • Severe diarrhea (≥ Grade 3) not controllable with medication or requires administration of total parenteral nutrition
  • Known gastrointestinal condition or procedure that could interfere with swallowing or the oral absorption of tolerance of MLN9708
  • Uncontrolled infection requiring systematic antibiotics
  • Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
  • Presence of other active malignancy with the exception of nonmelanoma skin cancer, cervical cancer, treated early-stage prostate cancer provided that prostate-specific antigen is within normal limit, or any completely resected carcinoma in situ
  • Female patients who are lactating or pregnant
  • Major surgery within 14 days before the first dose of study drug
  • Serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01318902

United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
Boston Medical Center
Boston, Massachusetts, United States, 02118
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New York
Mount Sinai Medical Center
New York, New York, United States, 10029
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
Canada, Ontario
University Health Network
Toronto, Ontario, Canada, M5G 2M9
CHU Limoges, Department of Hematology and Cell Therapy, Reference Center for AL amyloidosis
Limoges Cedex, France, 87042
Universitatsklinikum Heidelberg Innere Medizin V; Hamatologie, Onkologie und Rheumatologie
Heidelberg, Germany, D-69120
Amyloidosis Research & Treatment Center, Fondazione IRCCS Policlinico San Matteo
Pavia, Italy, 27100
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Millennium Pharmaceuticals, Inc. Identifier: NCT01318902     History of Changes
Other Study ID Numbers: C16007
2010-022497-13 ( EudraCT Number )
U1111-1168-1192 ( Registry Identifier: WHO (UTN ) )
First Posted: March 21, 2011    Key Record Dates
Last Update Posted: April 13, 2018
Last Verified: April 2018

Additional relevant MeSH terms:
Proteostasis Deficiencies
Metabolic Diseases
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Glycine Agents
Neurotransmitter Agents
Physiological Effects of Drugs