Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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.
 
ClinicalTrials.gov Identifier: NCT01939899
Recruitment Status : Completed
First Posted : September 11, 2013
Results First Posted : October 29, 2019
Last Update Posted : October 29, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Brief Summary:
The primary purpose of this study is to evaluate the anti-tumor activity of oral Ixazomib as measured by overall response rate (ORR) in adult participants with relapsed and/or refractory follicular lymphoma (FL).

Condition or disease Intervention/treatment Phase
Follicular Lymphoma Drug: IXAZOMIB Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (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
Actual Study Start Date : October 31, 2013
Actual Primary Completion Date : June 1, 2016
Actual Study Completion Date : March 23, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: IXAZOMIB
Ixazomib 4, 5.3 and 7 milligram (mg), orally, once on Days 1, 8 and 15 in a 28 day treatment cycle followed by a rest period of 13 days, for up to Cycle 29 or until disease progression or unacceptable toxicity at lead-in phase for participants with NHL. After completion of lead-in phase, participants will continue into Phase 2. Participants in Phase 2 will receive Ixazomib at RP2D dose, orally, once weekly on Days 1, 8 and 15 in a 28 day treatment cycle followed by a rest period of 13 days , for up to Cycle 29 or until disease progression or unacceptable toxicity in Phase 2 for participants with RRFL.
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.
Other Name: MLN9708




Primary Outcome Measures :
  1. Number of Participants With Overall Response Rate (ORR) [ Time Frame: Baseline up to Day 15 Cycle 29 (approximately up to Day 802) or until PD or the start of alternate therapies ]
    ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by the investigator using the international Working Group criteria for participants CR: disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions.


Secondary Outcome Measures :
  1. Lead-in Dose Finding Phase: Recommended Phase 2 Dose (RP2D) [ Time Frame: Baseline up to Cycle 1 Day 28 ]
  2. Progression Free Survival (PFS) [ Time Frame: Time from the date of first dose of study treatment to the date of first documented PD or death (approximately up to Day 802) ]
    PFS is defined as the time from the date of first dose of study treatment to the date of first documented PD or death. Participants without documentation of PD will be censored at the date of last response assessment that is SD or better. Participants without response assessment will be censored at the date of first dose.

  3. Phase 2: Rate of Disease Control [ Time Frame: Baseline or until occurrence of disease progression, unacceptable toxicities, or discontinuation of study due to any other reasons (approximately up to Day 805) ]
    Rate of disease control is defined as percentage of participants who achieved a SD or better for greater than or equal to (>=) 6 months.

  4. Time to Response (TTR) [ Time Frame: Time from the date of first dose of study treatment to the date of first documented PR or better response or death (approximately up to Day 802) ]
    TTR is defined as the time from the date of first dose of study treatment to the date of the first documentation of a PR or better response in a participant who responded.

  5. Duration of Response (DOR) [ Time Frame: Time from the date of first documentation of a response to the date of first documented PD (approximately up to Day 802) ]
    The DOR is defined as the time from the date of first documentation of a response to the date of first documented PD. Responders without documentation of PD will be censored at the date of last response assessment. DOR was categorized as CR+PR and CR.

  6. Phase 2: Number of Participants With Response Rates in PSMB1 Positive and PSMB1 Negative [ Time Frame: Baseline up to occurrence of disease progression, unacceptable toxicities, or discontinuation of study due to any other reasons (approximately up to Day 802) ]
  7. Number of Participants Experiencing 1 or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 30 days after last dose of study drug (approximately up to Day 832) ]
  8. Lead-in Dose Finding Phase: Cmax: Maximum Observed Plasma Concentration for Ixazomib [ Time Frame: Cycle 1, Days 1 and 15 pre-dose and at multiple time points (up to 168 hours) post-dose ]
  9. Lead-in Dose Finding Phase: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib [ Time Frame: Cycle 1, Days 1 and 15 pre-dose and at multiple time points (up to 168 hours) post-dose ]
  10. Lead-in Dose Finding Phase: AUC(0-168): Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Postdose for Ixazomib [ Time Frame: Cycle 1, Days 1 and 15 pre-dose and at multiple time points (up to 168 hours) post-dose ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female participants 18 years or older.
  • Participants must have a pathologically confirmed diagnosis of non-Hodgkin lymphoma (NHL) (for the lead-in dose-finding phase) and FL (for phase 2).
  • Participants must have radiographically or clinically measurable disease.
  • Participants 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 participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to practice true abstinence.
  • Male participants 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, participants 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 participants 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 participants 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 greater than (>) Grade 1 on the basis of the National Cancer Institute Common Terminology Criteria for Adverse Events (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 Cytochrome P450 1A2 (CYP1A2) or Cytochrome P450 3A (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.

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 ClinicalTrials.gov identifier (NCT number): NCT01939899


Locations
Layout table for location information
United States, Massachusetts
Boston, Massachusetts, United States
United States, New York
New York, New York, United States
United States, Tennessee
Nashville, Tennessee, United States
United States, Texas
Houston, Texas, United States
Belgium
Gent, Belgium
Leuven, Belgium
Wilrijk, Belgium
Canada, Quebec
Montreal, Quebec, Canada
United Kingdom
London, United Kingdom
Manchester, United Kingdom
Newcastle Upon Tyne, United Kingdom
Plymouth, United Kingdom
Southampton, United Kingdom
Sutton, United Kingdom
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Layout table for investigator information
Study Director: Medical Director Millennium Pharmaceuticals, Inc.
Layout table for additonal information
Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01939899    
Other Study ID Numbers: C16017
2013-002302-32 ( EudraCT Number )
U1111-1164-7551 ( Other Identifier: WHO )
166547 ( Registry Identifier: HC-CTD )
REec-2016-2137 ( Registry Identifier: REec )
13/EM/0373 ( Registry Identifier: NRES )
First Posted: September 11, 2013    Key Record Dates
Results First Posted: October 29, 2019
Last Update Posted: October 29, 2019
Last Verified: October 2019
Keywords provided by Takeda ( Millennium Pharmaceuticals, Inc. ):
MLN9708
Lymphoma
IXAZOMIB
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Lymphoma, Follicular
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Ixazomib
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action