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

NCT02158975 | Completed Phase 2 Results DMC

• 2 other identifiers: UMCC 2014.031HUM00088647
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Lymphoma, T-Cell

Outcome Measures

Primary Outcomes (1)

• 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).

  Up to 24 months after initiation of study treatment

Secondary Outcomes (4)

• Number Patients That Experience Adverse Events, Grades 3-5

  30 days after the last dose of study drug

• Median Progression Free Survival Time

  24 months after initiation of study treatment

• Median Overall Survival Time

  24 months after initiation of study treatment

• Duration of Response

  24 months after initiation of study treatment

Study Arms (1)

MLN9708

EXPERIMENTAL

MLN9708 4mg by mouth weekly (days 1, 8, 15) every 28 days.

Drug: MLN9708

Interventions

MLN9708 DRUG

MLN9708

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (1)

University of Michigan Hospital

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Lymphoma, T-Cell

Interventions

ixazomib

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Dr. Ryan Wilcox, M.D.
• Organization: University of Michigan Comprehensive Cancer Center

rywilcox@umich.edu

734-615-1482

Study Officials

• Ryan Wilcox, M.D., Ph.D.

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2014
• First Posted: June 9, 2014
• Study Start: September 1, 2014
• Primary Completion: October 1, 2016
• Study Completion: November 1, 2016
• Last Updated: November 13, 2017
• Results First Posted: November 13, 2017

Record last verified: 2017-10

Locations

US (1)