Trial of Duvelisib in Combination With Either Romidepsin or Bortezomib in Relapsed/Refractory T-cell Lymphomas

NCT02783625 | Completed Phase 1

• 1 other identifier: 16-042
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 11

Brief Summary

The purpose of this study is to test the safety of a study drug called duvelisib.

Conditions

Lymphoma; Relapsed/Refractory T-cell Lymphomas

Keywords

Duvelisib; Romidepsin; Bortezomib; 16-042

Outcome Measures

Primary Outcomes (1)

• maximum tolerated dose (MTD)

  There will be two parallel phase I studies using the 3+3 dose escalation scheme

  1 year

Secondary Outcomes (1)

• overall response rate (ORR)

  6 months

Study Arms (2)

Romidepsin + duvelisib

EXPERIMENTAL

Romidepsin/duvelisib: Cycle 1 and beyond Days 1, 8, 15\* Romidepsin IVPB over 4 hours, days 1, 8, 15 duvelisib by mouth twice daily, days 1-28

Drug: Romidepsin; Drug: duvelisib

Bortezomib + duvelisib

EXPERIMENTAL

Bortezomib/duvelisib: Cycle 1 and beyond Days 1, 4, 8, and 11\* Bortezomib subcutaneous injection, days 1, 4, 8, 11\*\* duvelisib by mouth twice daily, days 1-28

Drug: Bortezomib; Drug: duvelisib

Interventions

Romidepsin DRUG

Romidepsin + duvelisib

Bortezomib DRUG

Bortezomib + duvelisib

duvelisib DRUG

Also known as: IPI-145

Bortezomib + duvelisib; Romidepsin + duvelisib

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed T-cell lymphomas at the enrolling institution, including stage ≥ Ib CTCL, which has relapsed or progressed after at least one systemic therapy.
• Age ≥ 18
• Previous systemic anti-cancer therapy must have been discontinued at least 3 weeks prior to treatment. For the dose expansion phase, in progressing subjects, a 2 week washout may be allowed after discussion with the MSK Principal Investigator.
• ° Patients who have received localized RT as part of their immediate prior therapy may be allowed to enroll with shorter washout period after discussion with the MSK Principal Investigator.
• ECOG ≤ 2
• Meet the following laboratory criteria without use of growth factor support or platelet transfusions for 1 week:
• i) Absolute neutrophil count ≥ 1.0 K/mcl, ii) Platelet count ≥ 80 K/μl (in the expansion cohorts, if thrombocytopenia is due to bone marrow involvement platelet count must be ≥ 50 K/μL), iii) Patients enrolled in the dose escalation phase who are not enrolled on the expansion cohorts must have calculated creatinine clearance ≥ 50ml/min by Cockcroft-Gault formula. Patients enrolled in the Dose Expansion phase must have calculated creatinine clearance ≥ 40ml/min by Cockcroft-Gault formula.
• iv) Total bilirubin ≤ 1.5 x upper limit of normal (ULN) or ≤ 3 x ULN if documented hepatic involvement with lymphoma, or ≤ 5 x ULN if history of Gilbert's syndrome; AST (SGOT) and ALT (SGPT) ≤ 3 x ULN; ≤ 5 ULN if due to lymphoma involvement
• Measurable disease for dose expansion and lead in phase only.
• Measurable disease defined by:
• Revised International Working Group (Cheson, 2007) Classification for systemic lymphoma or
• Atypical and or malignant lymphocytes quantifiable by flow cytometry or morphology in blood
• or bone marrow mSWAT \> 0 or Sezary couny \>/= 1000 cells/ul
• Short course systemic corticosteroids for disease control, improvement of performance status or non-cancer indication (\< 7 days) must have been discontinued at least 6 days prior to study treatment. Stable ongoing corticosteroid use (≥ 30 days) up to an equivalent dose of 20 mg of prednisone is permissible.
• i) Topical steroids that have been used for \> 3 weeks may be continued (CTCL only). All other histologies (not CTCL): Topical steroids use is permissible without restriction

You may not qualify if:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Pregnant females. (Lactating females must agree not to breast feed while taking the study medications).
• Prior use of duvelisib if discontinued due to toxicity.
• For the romidepsin arm of the study, prior therapy with romidepsin if discontinued due to toxicity.
• For the bortezomib arm of the study, prior therapy with a proteasome inhibitor if discontinued due to toxicity.
• For the bortezomib arm of the study, patients with grade ≥2 peripheral neuropathy.
• History of chronic liver disease, veno-occlusive disease, or current alcohol abuse.
• Administration of a live vaccine within 6 weeks of first dose of study drug.
• Prior surgery or gastrointestinal dysfunction that may affect drug absorption (e.g., gastric bypass surgery, gastrectomy)
• Known seropositive and requiring anti-viral therapy for human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Subjects with chronic hepatitis B or C as defined as test .
• Subjects with positive Hep B serology. Subjects with a negative HBsAg and a positive HBcAb require an undetectable/negative hepatitis B DNA test (e.g., polymerase chain reaction \[PCR\] test) to be enrolled, and will require prophylactic antiviral treatment (e.g., F) initiated prior to the first dose of study drug, an continued until approximately 6 to 12 months after completion of study drug(s).
• Patients with positive hepatitis C virus Ab
• Subjects with active EBV unrelated to underlying lymphoma (positive serology for anti-EBV VCA IgM antibody and negative for anti-EBV EBNA IgG antibody, or clinical manifestations and positive EBV PCR consistent with active EBV infection.
• Subject with active CMV (positive serology for anti-CMV IgM antibody and negative for anti-CMV IgG antibody and positive CMV PCR with clinical manifestations consistent with active CMV infection) and requiring therapy will be excluded from participation in the study. Carriers will be monitored per institutional guidelines.
• Receiving systemic therapy for another primary malignancy (other than T-cell lymphoma)

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Dana-Farber Cancer Institute: collaborator
• Stanford University: collaborator

Study Sites (11)

Stanford University Medical Center

Stanford, California, 94305-5408, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Washington School of Medicine in St. Louis

St Louis, Missouri, 63110, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center Basking Ridge (Limited protocol activities)

Basking Ridge, New Jersey, United States

Location

Memorial Sloan Kettering Monmouth (Limited protocol activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Cancer Center @ Commack (Limitied protocol activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited protocol activities)

Harrison, New York, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited protocol activities)

Uniondale, New York, 11553, United States

Location

Related Publications (1)

• Horwitz SM, Nirmal AJ, Rahman J, Xu R, Drill E, Galasso N, Ganesan N, Davey T, Hancock H, Perez L, Maccaro C, Bahgat A, Marzouk E, Cathcart E, Moskowitz A, Noy A, Kumar A, Jacobsen E, Fisher DC, Mehta-Shah N, Kim YH, Khodadoust M, Kotlov N, Nikitina A, Kudryashova O, Zubareva V, Zornikova K, Shin N, Sorokina M, Degryse S, Postovalova E, Bagaev A, Hosszu K, McAvoy D, Boelens JJ, Wu W, Ciantra Z, Appelt JW, Trevisani C, Amaka S, Weinstock DM, Vardhana SA. Duvelisib plus romidepsin in relapsed/refractory T cell lymphomas: a phase 1b/2a trial. Nat Med. 2024 Sep;30(9):2517-2527. doi: 10.1038/s41591-024-03076-6. Epub 2024 Jun 17.

  PMID: 38886623 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Lymphoma; Lymphoma, T-Cell

Interventions

romidepsin; Bortezomib; duvelisib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Steven Horwitz, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 24, 2016
• First Posted: May 26, 2016
• Study Start: May 23, 2016
• Primary Completion: April 21, 2026
• Study Completion: April 21, 2026
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

US (11)