Study of Pembrolizumab (MK-3475) in Combination With Romidepsin

NCT03278782 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2017-0272NCI-2018-01051
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects of pembrolizumab and romidepsin and to see how well they work in treating participants with peripheral T-cell lymphoma that has come back or that does not respond to treatment. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Romidepsin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and romidepsin may work better than pembrolizumab alone in treating participants with recurrent or refractory peripheral T-cell lymphoma.

Conditions

Recurrent Anaplastic Large Cell Lymphoma; Recurrent Angioimmunoblastic T-Cell Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Angioimmunoblastic T-Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity (Phase I)

  As determined by incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The phase I portion of the study follows standard 3+3 design. The 6 patients tested in the phase I at the dose finally determined as recommended phase II dose (RP2D) will be included in the response assessment of phase II study. Toxicity data will be summarized by type and severity for all patients who received the treatment regardless of the eligibility nor the duration or dose of the treatment received.

  Up to 21 days

• Overall response (OR) (Phase II)

  As determined by Lugano Revised Response Criteria, International Society for Cutaneous Lymphomas (ISCL) for Research, and the European Organization for Research and Treatment of Cancer (EORTC) criteria. Response is defined by the best response during the therapy, as defined by the schedule of response evaluation. Summary statistics will be provided for continuous variables and categorical variables. The complete response (CR) and OR rates and their 95% confidence intervals will be reported. Fisher's exact test will be used to evaluate the association between two categorical variables. Wilcoxon rank sum test will be used to assess the difference in a continuous variable between patient groups.

  Up to 3 years

Secondary Outcomes (4)

• Progression-free survival (PFS)

  From the date of study registration and the date of progression, recurrence, or death without progression, whichever comes first, assessed up to 3 years

• Overall survival

  From the date of study registration to the date of death from any cause, assessed up to 3 years

• Complete response

  Up to 3 years

• Duration of response

  Up to 3 years

Study Arms (1)

Treatment (romidepsin, pembrolizumab)

EXPERIMENTAL

Participants receive romidepsin IV over 4 hours on days 1 and 8 or day 8 of cycle 1 and days 1 and 8 of subsequent cycles and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.

Biological: Pembrolizumab; Drug: Romidepsin

Interventions

Romidepsin DRUG

Given IV

Also known as: Antibiotic FR 901228, Depsipeptide, FK228, FR901228, Istodax, N-[(3S,4E)-3-Hydroxy-7-mercapto-1-oxo-4-heptenyl]-D-valyl-D-cysteinyl-(2Z)-2-amino-2-butenoyl-L-valine, (4->1) Lactone, Cyclic

Treatment (romidepsin, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (romidepsin, pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• Patients with peripheral T-cell lymphoma (including but not limited to PTCL-NOS, angioimmunoblastic T-cell lymphoma, anaplastic large T-cell lymphoma). Patients with mycosis fungoides with large cell transformation with measurable disease are eligible.
• Disease status defined as refractory to or relapsed after ≥ 1 prior treatment lines.
• Patients irrespective of transplant eligibility status can be enrolled; however patients can be seen by SCT team in anticipation for SCT.
• Subjects with ALK+ ALCL should have been treated with, be ineligible for, or have refused chemotherapy and brentuximab prior to enrollment on the current study.
• Patients with a measurable disease, defined by a node or mass with the longest diameter ≥ 1.5cm.
• In order to be eligible for participation in this trial, the subject must:
• Be willing and able to provide written informed consent/assent for the trial.
• Be 18 years of age on day of signing informed consent.
• Patients with PTCL should have radiographically measurable disease \>/= 1.5cm.
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 12 weeks(84 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen.
• Have a performance status of 0, 1 or 2 on the ECOG Performance Scale.
• Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 14 days of treatment initiation.
• Table 1 Adequate Organ Function Laboratory Values System Laboratory Value
• Hematological
• Absolute neutrophil count (ANC) ≥ 1000 /mcL

You may not qualify if:

• The subject must be excluded from participating in the trial if the subject:
• Is currently receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency, is receiving systemic steroids above physiologic dose (\>10mg/day prednisone or equivalent) within 5 half lives after the last dose of steroid of start of therapy or is receiving any other form of immunosuppressive therapy.
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment within the last 3 years Exceptions include basal cell carcinoma of the skin, resected renal cell cancer or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has known history of non-infectious pneumonitis that required systemic steroid use, or has active pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Lymphoma, Large-Cell, Anaplastic; Immunoblastic Lymphadenopathy; Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous; Lymphoma, T-Cell

Interventions

pembrolizumab; romidepsin; Depsipeptides; Lactones

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; Lymphadenopathy

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Organic Chemicals

Study Officials

• Swaminathan P Iyer, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 8, 2017
• First Posted: September 12, 2017
• Study Start: November 14, 2017
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2027
• Last Updated: January 9, 2026

Record last verified: 2026-01

Locations

US (1)