Study of Ixazomib and Romidepsin in Peripheral T-cell Lymphoma (PTCL)

NCT03547700 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: BTCRC-HEM15-028
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 7

Brief Summary

Single arm phase I/II study of ixazomib and romidepsin in relapsed/refractory PTCL. Each cycle is 28 days. Patients will continue to receive therapy until progressive disease, unacceptable toxicity, or if any other withdrawal criteria are met. The phase I study includes three dose levels. The phase II study will include treatment with ixazomib and romidepsin at the MTD established in the Phase I study.

Conditions

Lymphoma, T-Cell, Peripheral

Outcome Measures

Primary Outcomes (2)

• Phase I: Maximum Tolerated Dose (MTD)

  MTD is the dose level with a model-estimated rate of Dose Limiting Toxicities (DLT) closest to 25% after 36 patients have been enrolled. The maximum tolerated dose could not be determined because the trial was terminated early, however the number of participants who experienced DLTs found at each dose level is reported in a new outcome measure.

  From first dose of treatment through the 1st cycle (28 days)

• Phase II: Complete Response Rate (CR)

  The complete response (CR) rate of this combination in relapsed/refractory PTCL is defined as complete metabolic response recorded from first day of treatment until disease progression or initiation of new antineoplastic therapy, as per the Lugano response criteria.

  36 months

Secondary Outcomes (4)

• Phase II: Overall Response Rate (ORR)

  36 months

• Phase II: Duration of Response (DOR)

  36 months

• Phase II: Time To Next Treatment (TTNT)

  36 months

• Phase II: Overall Survival (OS)

  36 months

Study Arms (1)

Phase I: Romidepsin plus Ixazomib

EXPERIMENTAL

The phase I study includes three dose levels (DL) for romidepsin: DL4: 10 mg/m2 on Days 1, 8, 15; DL5: 14 mg/m2 Days 1, 8; DL6: 14 mg/m2 Days 1, 8, 15. Ixazomib is 4 mg PO Days 1, 8, 15. The phase II study will include treatment with ixazomib and romidepsin at the MTD established in the Phase I study. Each cycle is 28 days and patients will receive treatment until progressive disease, unacceptable toxicity, or if any other withdrawal criteria are met.

Drug: Romidepsin; Drug: Ixazomib

Interventions

Romidepsin DRUG

Romidepsin is a histone deacetylase (HDAC) inhibitor. HDACs catalyze the removal of acetyl groups from acetylated lysine residues in histones, resulting in the modulation of gene expression.

Also known as: Istodax

Phase I: Romidepsin plus Ixazomib

Ixazomib DRUG

Ixazomib is a reversible proteasome inhibitor. Ixazomib preferentially binds and inhibits the chymotrypsin-like activity of the beta 5 subunit of the 20S proteasome.

Also known as: Ninlaro

Phase I: Romidepsin plus Ixazomib

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0-2 within 14 days prior to registration.
• Histological confirmation of peripheral T-cell lymphoma (PTCL) and biopsy confirmation of disease relapse (after initial or any subsequent salvage therapy).
• Documented disease progression after receiving at least one prior therapeutic regimen.
• Prior cancer treatment must be completed at least 28 days prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤ Grade 1 or baseline. Systemic steroids at a dose less than the equivalent of 10 mg/day of prednisone and inhaled, nasal, and topical steroids are permitted. Intermittent dexamethasone for the treatment of nausea/emesis is also permitted.
• Absolute Neutrophil Count (ANC) ≥ 1000/mm3
• Platelets (Plt) ≥ 75,000/mm3
• Calculated creatinine clearance ≥ 30 cc/min using the Cockcroft-Gault formula
• Bilirubin ≤ 1.5 × upper limit of normal (ULN), (exception of Gilbert disease)
• Aspartate aminotransferase (AST) ≤ 3 × ULN, if known hepatic involvement then ≤ 5 × ULN
• Alanine aminotransferase (ALT) ≤ 3 × ULN, if known hepatic involvement then ≤ 5 × ULN
• Females of childbearing potential must have a negative serum pregnancy test within 14 days prior to registration. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
• Males must be willing to abstain from donating sperm or semen from the time of informed consent until 90 days after treatment discontinuation.
• The subject must have the ability to understand and comply with study procedures for the entire length of the study, as determined by the treating physician or protocol designee.

You may not qualify if:

• A history of, or a concurrent, clinically significant illness, medical condition or laboratory abnormality that, in the investigator's opinion, could affect the conduct of the study.
• Active infection requiring systemic therapy
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least two years.
• Active central nervous system (CNS) lymphoma
• Major surgery or radiation therapy within 28 days of study registration
• Uncontrolled infectious disease, including active herpes simplex or herpes zoster
• Known positive test for Hepatitis B surface antigen, Hepatitis C, or HIV. NOTE: testing is not required.
• Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of oral medications including difficulty swallowing, as determined by the treating physician.
• Evidence of uncontrolled cardiovascular conditions, including uncontrolled hypertension, cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
• Q-T interval, based on Bazett-corrected interval \> 0.45 sec
• Treatment with any investigational drug within 28 days prior to registration.
• Peripheral neuropathy ≥ grade 2
• Prior treatment with bortezomib, ixazomib, or romidepsin.
• Systemic treatment, within 14 days, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• Takeda: collaborator
• Big Ten Cancer Research Consortium: collaborator

Study Sites (7)

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Center (Wayne State University)

Detroit, Michigan, 48201, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

MeSH Terms

Conditions

Lymphoma, T-Cell, Peripheral

Interventions

romidepsin; ixazomib

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; 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: Fauzia Sharmin
• Organization: HCRN

fsharmin@hoosiercancer.org

317-634-5842

Study Officials

• Ryan Wilcox, MD, PhD

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2018
• First Posted: June 6, 2018
• Study Start: September 26, 2018
• Primary Completion: August 27, 2020
• Study Completion: August 27, 2020
• Last Updated: May 6, 2026
• Results First Posted: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)