Phase 2 Study of Oral IXAZOMIB in Adult Patients With Relapsed and/or Refractory Follicular Lymphoma

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:
NCT01939899
First received: August 28, 2013
Last updated: June 12, 2014
Last verified: June 2014
  Purpose

This is an open-label, multicenter, phase 2 study to evaluate the efficacy and safety of oral IXAZOMIB in adult patients with follicular lymphoma (FL) that is relapsed and/or refractory to prior treatment.


Condition Intervention Phase
Follicular Lymphoma
Drug: IXAZOMIB
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Multicenter, Phase 2 Study of Oral IXAZOMIB (MLN9708) in Adult Patients With Relapsed and/or Refractory Follicular Lymphoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Overall Response (Complete Response (CR) + Partial Response(PR)) Rate (ORR) [ Time Frame: Time from the start of treatment to the occurrence of disease progression, unacceptable toxicities, or discontinuation of study due to any other reasons (up to approximately 24 months) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Recommended Phase 2 Dose (RP2D) [ Time Frame: Approximately 8 months after dosing the first patient ] [ Designated as safety issue: No ]
  • Progression Free Survival (PFS) [ Time Frame: Up to a total of 24 months after first dose or until disease progression, withdrawal from study, or death ] [ Designated as safety issue: No ]
  • Rate of Disease Control [ Time Frame: Time from the start of treatment to the occurrence of disease progression, unacceptable toxicities, or discontinuation of study due to any other reasons (up to approximately 24 months) ] [ Designated as safety issue: No ]
  • Time to Response (TTR) [ Time Frame: Time from the date of registration to the date at which the patient's objective status is first noted to be a CR or PR (assessed up to approximately 24 months) ] [ Designated as safety issue: No ]
  • Duration of Response (DOR) [ Time Frame: Time from the date at which the patient's objective status is first noted to be a CR or PR to the earliest date progression is documented (assessed up to approximately 24 months) ] [ Designated as safety issue: No ]
  • Response rates in FL patients positive versus negative for the proteasome subunit beta type-1 (PSMB1) polymorphic marker [ Time Frame: Time from the start of treatment to the occurrence of disease progression, unacceptable toxicities, or discontinuation of study due to any other reasons (up to approximately 24 months) ] [ Designated as safety issue: No ]
  • Number of participants with Adverse Events (AE) or Serious Adverse Events (SAE) [ Time Frame: Signing of informed consent through 30 days after last dose ] [ Designated as safety issue: Yes ]
  • Plasma PK parameters including Maximum Concentration (Cmax), Single-dose time to reach maximum plasma concentration (Tmax), Area under the plasma concentration versus time curve (AUC) from zero to time of last quantifiable plasma concentration (AUClast) [ Time Frame: Days 1-3, 5, 8, 15-17, 19 and 22 during Cycle 1 and Day 1 during Cycles 2-4 of each lead-in dose finding cohort ] [ Designated as safety issue: No ]

Estimated Enrollment: 58
Study Start Date: November 2013
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IXAZOMIB Drug: IXAZOMIB
Each 28-day treatment cycle will include oral administration of IXAZOMIB on Days 1, 8, and 15 followed by a rest period of 13 days.

  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
  • Patients must have a pathologically confirmed diagnosis of non-Hodgkin lymphoma (NHL) (for the lead-in dose-finding phase) and FL (for phase 2)
  • Patients must have radiographically or clinically measurable disease
  • Patients must be relapsed and/or refractory after at least 1 prior therapy (excluding radiation) with documented progressive disease at the time of enrollment
  • 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 practice true abstinence
  • Male patients who agree to practice effective barrier contraception or agree to practice true abstinence
  • Voluntary written consent
  • Suitable venous access
  • Appropriate clinical laboratory values as defined in the protocol
  • Recovered from toxicities of prior anticancer therapy
  • If the trial proceeds to the second step on the basis of the tandem 2-step design, patients must be confirmed PSMB1 positive at the central laboratory before treatment

Exclusion Criteria

  • Peripheral neuropathy that is greater or equal to Grade 2 or Grade 1 with pain
  • Female patients who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period
  • Autologous stem cell transplant within 6 months before Day 1 of Cycle 1, or prior allogeneic stem cell transplant at any time
  • Major surgery within 14 days before the first dose of study drug
  • Infection requiring systemic antibiotic therapy or other serious infection within 14 days before the first dose of study drug
  • Comorbid systemic illnesses or other severe concurrent disease that, 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
  • Evidence of current uncontrolled cardiovascular conditions including uncontrolled hypertension, severe uncontrolled ventricular arrhythmias, unstable angina, New York Heart Association (NYHA) Class III or IV cardiac disease, or myocardial infarction within the past 6 months
  • Diarrhea > Grade 1 on the basis of the NCI CTCAE categorization
  • Systemic antineoplastic (including glucocorticoids > the equivalent of 15 mg of prednisone daily), experimental, or radiation therapy within 21 days before the first dose of study drug
  • Prior treatment with rituximab or other unconjugated antibody treatment within 42 days (21 days if clear evidence of progressive disease or immediate treatment is mandated)
  • Treatment with radioimmunoconjugates or toxin immunoconjugates within 12 weeks before the first dosing of study treatment
  • Systemic treatment with strong inhibitors of CYP1A2 or CYP3A, or strong CYP3A inducers within 14 days before the first dose of IXAZOMIB - Ongoing systemic therapy with corticosteroids
  • Central nervous system (CNS) involvement that is clinically uncontrolled or newly diagnosed in the last 4 months
  • Ongoing or active systemic viral infection, known human immunodeficiency virus(HIV) positive, known active hepatitis B virus or known active hepatitis C virus
  • Diagnosed or treated for another malignancy within 2 years before study enrollment 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
  • Platelet transfusions within 3 days before the 1st dose of study drug
  • Inability to swallow capsules, or inability or unwillingness to avoid taking anything by mouth except for water and prescribed medication for 2 hours before and 1 hour after dose of IXAZOMIB - Known allergy to boron or excipients in the formulation
  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: NCT01939899

Contacts
Contact: For an updated listing of recruitment sites contact: Millennium Medical and Drug Information Center 1-877-674-3784 medical@mlnm.com

Locations
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
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: NCT01939899     History of Changes
Other Study ID Numbers: C16017, 2013-002302-32
Study First Received: August 28, 2013
Last Updated: June 12, 2014
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency
Canada: Health Canada

Keywords provided by Millennium Pharmaceuticals, Inc.:
MLN9708
Lymphoma
IXAZOMIB

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on October 21, 2014