- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02158975
Open-label, Phase II Study of MLN9708 in Patients With Relapsed/Refractory Cutaneous and Peripheral T-cell Lymphomas
Open-label, Single-center Phase II Study of MLN9708 (Ixazomib) in Patients With Relapsed/Refractory Cutaneous and Peripheral T-cell Lymphomas
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.
Study Overview
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Michigan
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Ann Arbor, Michigan, United States, 48109
- University of Michigan Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: MLN9708
MLN9708 4mg by mouth weekly (days 1, 8, 15) every 28 days.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate
Time Frame: Up to 24 months after initiation of study treatment
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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).
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Up to 24 months after initiation of study treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number Patients That Experience Adverse Events, Grades 3-5
Time Frame: 30 days after the last dose of study drug
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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.
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30 days after the last dose of study drug
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Median Progression Free Survival Time
Time Frame: 24 months after initiation of study treatment
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Progression Free Survival (PFS) is defined as the time from study start until disease progression or death.
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24 months after initiation of study treatment
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Median Overall Survival Time
Time Frame: 24 months after initiation of study treatment
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Overall Survival (OS) is defined as the time from study start until death.
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24 months after initiation of study treatment
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Duration of Response
Time Frame: 24 months after initiation of study treatment
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Time from documentation of tumor response to disease progression.
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24 months after initiation of study treatment
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Collaborators and Investigators
Investigators
- Principal Investigator: Ryan Wilcox, M.D., Ph.D., University of Michigan Rogel Cancer Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Lymphoma
- Lymphoma, T-Cell
- Lymphoma, T-Cell, Peripheral
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protease Inhibitors
- Ixazomib
Other Study ID Numbers
- UMCC 2014.031
- HUM00088647 (Other Identifier: University of Michigan)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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