Lymphoma, T-CellPhase 2NCT02158975
Open-label, Phase II Study of MLN9708 in Patients With Relapsed/Refractory Cutaneous and Peripheral T-cell Lymphomas
A Phase 2 study testing MLN9708 in people with Lymphoma, T-Cell, run by University of Michigan Rogel Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, T-Cell
- What is being tested?
- MLN9708
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2014to Nov 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Michigan Hospital
Ann Arbor, Michigan, 48109
About this study
Official title: 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.
Read the 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.
- Conditions
- Lymphoma, T-Cell
- Being tested
- MLN9708
- Medical subject headings
- Lymphoma, T-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MLN9708Drug
| Study group | Role | What they receive |
|---|---|---|
| MLN9708 | Experimental | MLN9708 4mg by mouth weekly (days 1, 8, 15) every 28 days. Receives: Drug: MLN9708 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate
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).
Measured: Up to 24 months after initiation of study treatment
Secondary outcomes (4)
Number Patients That Experience Adverse Events, Grades 3-5
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.
Measured: 30 days after the last dose of study drug
Median Progression Free Survival Time
Progression Free Survival (PFS) is defined as the time from study start until disease progression or death.
Measured: 24 months after initiation of study treatment
Median Overall Survival Time
Overall Survival (OS) is defined as the time from study start until death.
Measured: 24 months after initiation of study treatment
Duration of Response
Time from documentation of tumor response to disease progression.
Measured: 24 months after initiation of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2014 (estimated)
- Study startSep 2014
- Primary completionOct 2016
- Study completionNov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Lymphoma, T-CellStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ryan Wilcox, M.D., Ph.D., Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02158975
- Sponsor's protocol ID
- UMCC 2014.031
- Other IDs
- HUM00088647
- Status last verified
- Oct 2017
- First submitted
- 5 Jun 2014
- Last updated
- 13 Nov 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label, Single-center Phase II Study of MLN9708 (Ixazomib) in Patients With Relapsed/Refractory Cutaneous and Peripheral T-cell Lymphomas
- ClinicalTrials.gov ID
- NCT02158975
- Acronym / sponsor ID
- UMCC 2014.031
- Conditions
- Lymphoma, T-Cell
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Study start
- Sep 2014
- Primary completion
- Oct 2016 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 9 Jun 2014 (estimated)
- Results
- Posted 13 Nov 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MLN9708 | Experimental | Drug: MLN9708MLN9708 4mg by mouth weekly (days 1, 8, 15) every 28 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MLN9708 | Drug | MLN9708 |
Primary outcome
Objective Response Rate
Time frame: Up to 24 months after initiation of study treatment
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).
4 secondary outcomes
Number Patients That Experience Adverse Events, Grades 3-5
Time frame: 30 days after the last dose of study drug
Median Progression Free Survival Time
Time frame: 24 months after initiation of study treatment
Median Overall Survival Time
Time frame: 24 months after initiation of study treatment
Duration of Response
Time frame: 24 months after initiation of study treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ryan Wilcox, M.D., Ph.D. principal investigator
University of Michigan Rogel Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MLN9708 in people with Lymphoma, T-Cell, run by University of Michigan Rogel Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Nov 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (time frame: Up to 24 months after initiation of study treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2017.