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NCT02158975 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE2
Status at capture
COMPLETED
Registry last update
2017-11-13

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Objective Response Rate

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outcome · POSTED

Number Patients That Experience Adverse Events, Grades 3-5

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outcome · POSTED

Median Progression Free Survival Time

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outcome · POSTED

Median Overall Survival Time

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outcome · POSTED

Duration of Response

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility 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.
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    MLN9708 4mg by mouth weekly (days 1, 8, 15) every 28 days.
    intervention Names
    1. Drug: MLN9708
    label
    MLN9708
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. MLN9708
    name
    MLN9708
    type
    DRUG
Study design
allocation
NA
intervention Model
SINGLE_GROUP
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
13
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    The percentage of patients with an objective response rate will be determined. The overall response will be based on response in each compartment (skin, blood, lymph nodes and viscera) using a global composite scoring system. Objective response is considered (CR) Complete Response (Complete disappearance of all clinical evidence of disease), CRu (Complete Response Unconfirmed), or (PR) Partial Response (Regression of measurable disease).
    measure
    Objective Response Rate
    time Frame
    Up to 24 months after initiation of study treatment
secondary Outcomes
  1. description
    To assess the safety and tolerability of MLN9708, the number of patients experiencing Adverse Events (AEs) greater than or equal to grade 3 will be recorded.
    measure
    Number Patients That Experience Adverse Events, Grades 3-5
    time Frame
    30 days after the last dose of study drug
  2. description
    Progression Free Survival (PFS) is defined as the time from study start until disease progression or death.
    measure
    Median Progression Free Survival Time
    time Frame
    24 months after initiation of study treatment
  3. description
    Overall Survival (OS) is defined as the time from study start until death.
    measure
    Median Overall Survival Time
    time Frame
    24 months after initiation of study treatment
  4. description
    Time from documentation of tumor response to disease progression.
    measure
    Duration of Response
    time Frame
    24 months after initiation of study treatment
Full study description
brief Summary
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.
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.
Source references
Source notices and limitations
    Discovery and provenance
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      payload
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      true
      id
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      nct id
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      occurrences
      1. context exact
        NCT02158975
        end
        11
        exact text
        NCT02158975
        start
        0
      offset unit
      unicode_code_points
      query cond
      Peripheral T-Cell Non-Hodgkin Lymphoma
      query disease state id
      ds-peripheral-t-cell-non-hodgkin-lymphoma
      source file
      /Users/arunverma/Documents/ChatGPT/Cancer Statistics Website/research-data/2026-09-10/clinicaltrials-condition/round-0000/raw/cond-peripheral-t-cell-non-hodgkin-lymphoma-000.json
      source file sha256
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      source json pointer
      /studies/104/protocolSection/identificationModule/nctId
      source kind
      ctgov_condition_query
      source record id
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      source string basis
      parsed_JSON_string_unmodified
      source string sha256
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    Preserved source evidence · Not medical advice