Study of Oral MLN9708 in Adult Patients With Relapsed or Refractory Light Chain Amyloidosis

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01318902
First received: March 15, 2011
Last updated: January 17, 2014
Last verified: January 2014
  Purpose

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 MLN9708 administered orally.


Condition Intervention Phase
Light-Chain Amyloidosis
Drug: MLN9708
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Dose-Escalation, Phase 1 Study of the Oral Formulation of MLN9708 Administered Weekly in Adult Patients With Relapsed or Refractory Light-Chain Amyloidosis Who Require Further Treatment

Resource links provided by NLM:


Further study details as provided by Millennium Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
    Based on toxicity and efficacy outcomes


Secondary Outcome Measures:
  • Whole blood 20S proteasome activity profile and inhibition parameters of multiple-dose oral MLN9708 [ Time Frame: Days 1,2,8,15,16,22 ] [ Designated as safety issue: No ]
    Plasma pharmacokinetic and whole blood pharmacodynamic effect of MLN9708

  • 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 ] [ Designated as safety issue: No ]
    Complete response, very good partial response, partial response

  • 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 ] [ Designated as safety issue: No ]
    According to standardized criteria

  • Time to hematologic and organ disease progression [ Time Frame: Until evidence of hematologic and/or disease progression ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    Progression free survival

  • 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 ] [ Designated as safety issue: No ]

Enrollment: 27
Study Start Date: May 2011
Estimated Study Completion Date: February 2014
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

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

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
  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: NCT01318902

Locations
United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
Boston Medical Center
Boston, Massachusetts, United States, 02118
United States, Michigan
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
Canada, Ontario
University Health Network, Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
France
CHU Limoges
Limoges, France, 87000
Germany
University of Heidelberg
Heidelberg, Germany, D-69120
Italy
Amyloidosis Research & Treatment Center
Pavia, Italy, 27100
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01318902     History of Changes
Other Study ID Numbers: C16007, 2010-022497-13
Study First Received: March 15, 2011
Last Updated: January 17, 2014
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases

ClinicalTrials.gov processed this record on August 28, 2014