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Open-label, Phase II Study of MLN9708 in Patients With Relapsed/Refractory Cutaneous and Peripheral T-cell Lymphomas

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT02158975
First received: June 5, 2014
Last updated: December 15, 2016
Last verified: December 2016
  Purpose

Historically cutaneous and peripheral T-cell lymphomas have response rates of approximately 30% to standard chemotherapy regimens. We alternatively hypothesize that MLN9708 will be active in this disease and will improve best objective response.

We will also determine the extent to which MLN9708 inhibits GATA-3 (Trans-acting T-cell-specific transcription factor) expression, which is associated with poor prognosis, and whether GATA-3 expression represents a novel predictive biomarker for MLN9708 sensitivity.


Condition Intervention Phase
Lymphoma, T-Cell
Drug: MLN9708
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open-label, Single-center Phase II Study of MLN9708 (Ixazomib) in Patients With Relapsed/Refractory Cutaneous and Peripheral T-cell Lymphomas

Resource links provided by NLM:


Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:
  • Objective Response Rate [ Time Frame: 24 months after initiation of study treatment ]
    Objective response is considered CR (Complete Response), CRu (Complete Response Unknown), or PR (Partial Response) and will be measured after every 2nd cycle of treatment until the 6th cycle, then every 3 months until 24 months, then every 6 months, all until disease progression or death. All patients receiving any MLN9708 therapy per protocol are considered evaluable for the primary endpoint; however, patients not able to receive at least 2-cycles of MLN9708 with an accompanying response assessment will be considered treatment failures.


Secondary Outcome Measures:
  • Number of Adverse Events, Grades 3-5 [ Time Frame: 30 days after the last dose of study drug ]
    To assess the safety and tolerability of MLN9708, the incidence of Adverse Events (AEs), as well as severity, seriousness and relatedness will be recorded.

  • Progression Free Survival Time [ Time Frame: 24 months after initiation of study treatment ]
    Time from study start until disease progression or death.

  • Overall Survival Time [ Time Frame: 24 months after initiation of study treatment ]
    Time from study start until death.

  • Duration of Response [ Time Frame: 24 months after initiation of study treatment ]
    Time from documentation of tumor response to disease progression.


Enrollment: 13
Study Start Date: September 2014
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MLN9708
MLN9708 4mg by mouth weekly (days 1, 8, 15) every 28 days.
Drug: MLN9708

Detailed Description:
Up to 25 patients meeting the inclusion and exclusion criteria will be enrolled into this trial in two stages. All enrolled patients will be treated with MLN9708 4 mg PO weekly (days 1, 8, 15 every 28 days) until disease progression or unacceptable toxicity. In the initial stage of the study a total of 11 patients will be enrolled and treated with MLN9708. Should at least 4 patients exhibit a response (CR/CRu, PR), the second stage of 14 patients will open for enrollment. Efficacy will be assessed radiographically, by peripheral blood and bone marrow examination (when indicated), and physical exam every 8 weeks. Safety will be assessed by periodic physical exams, laboratory studies, and adverse events. All patients will have a follow-up visit 35 days (+/-7 days) following the last study drug treatment. Patients with accessible tumor tissue will be asked to undergo a biopsy for a fresh tissue sample for assessment of GATA-3 expression. Archived tissue samples from the initial diagnostic biopsy and the most recent lymphoma biopsy will be obtained in the event a fresh tumor biopsy cannot be obtained. Patients with GATA-3+ TCL and accessible tumor tissue will undergo a tumor biopsy at day 21 (+/- 7 days) of cycle 1. All baseline fresh or archived tissue will undergo central pathology review to confirm the diagnosis of TCL. The rationale for proteasome inhibition in T-cell lymphomas, based on the pre-clinical (and previous phase II) data, is compelling. Therefore, this phase II study will not be restricted to patients with GATA-3 expressing lymphomas.
  Eligibility

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

Inclusion Criteria:

  • Male or female patients 18 years or older at the time of enrollment.
  • Voluntary written consent must be given.
  • Female patients who are postmenopausal for at least 1 year before the screening visit, OR surgically sterile, OR agree to practice 2 effective methods of contraception, at the same time, through 90 days after the last dose of study drug, AND adhere to the guidelines of any treatment-specific pregnancy prevention program, OR agree to practice true abstinence.
  • Male patients must agree to practice effective barrier contraception through 90 days after the last dose of study drug, OR adhere to the guidelines of any treatment-specific pregnancy prevention program, OR agree to practice true abstinence.
  • Patients must have histologically proven T-cell lymphoma, including Peripheral T-cell lymphoma, Angioimmunoblastic T-cell lymphoma, Anaplastic large cell lymphoma (ALK positive), Anaplastic large cell lymphoma (ALK negative), Mycosis fungoides, Sezary syndrome.
  • CTCL patients must have stage IIb-IV disease.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
  • Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet count ≥ 75,000/mm3.
  • Platelet transfusions are not allowed within 3 days before study enrollment.
  • Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN).
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ to 3 x ULN.
  • Creatinine clearance ≥30 mL/min.
  • Documented disease progression after receiving at least one prior therapeutic regimen.

Exclusion Criteria:

  • Female patients who are lactating or have a positive serum pregnancy test.
  • Failure to have recovered (ie, less than or equal to Grade 1 toxicity) from the reversible effects of prior chemotherapy.
  • Major surgery within 14 days of enrollment.
  • Radiotherapy within 14 days of enrollment. If the field is small, 7 days will be considered a sufficient interval between treatment and administration of the MLN9708.
  • Known central nervous system involvement.
  • Infection requiring systemic intravenous antibiotic therapy or other serious infection within 7 days before study enrollment.
  • Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
  • Systemic treatment, within 14 days before the first dose of MLN9708, with strong inhibitors of CYP1A2, strong inhibitors of CYP3A or strong CYP3A inducers or use of Ginkgo biloba or St. John's wort.
  • Ongoing or active systemic infection, active hepatitis B or C virus infection, or HIV positive.
  • Any serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol.
  • Known allergy to any of the study medications, their analogues, or excipients.
  • Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of MLN9708 including difficulty swallowing.
  • 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. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
  • Patient has greater than or equal to Grade 3 peripheral neuropathy, or Grade 2 with pain on clinical examination during the screening period.
  • Participation in other clinical trials with other investigational agents not included in this trial, within 21days of the start of this trial and throughout the duration of this trial.
  • Prior allogeneic hematopoietic stem cell transplant.
  • Prior autologous hematopoietic stem cell transplant within 90 days of study entry.
  • Prior treatment with bortezomib.
  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: NCT02158975

Locations
United States, Michigan
University of Michigan Hospital
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan Cancer Center
Investigators
Principal Investigator: Ryan Wilcox, M.D., Ph.D. University of Michigan Cancer Center
  More Information

Responsible Party: University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT02158975     History of Changes
Other Study ID Numbers: UMCC 2014.031
HUM00088647 ( Other Identifier: University of Michigan )
Study First Received: June 5, 2014
Last Updated: December 15, 2016

Additional relevant MeSH terms:
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Ixazomib
Glycine
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Glycine Agents
Neurotransmitter Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on March 29, 2017