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

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ClinicalTrials.gov Identifier: NCT03278782
Recruitment Status : Recruiting
First Posted : September 12, 2017
Last Update Posted : August 14, 2018
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to learn if it is safe to give pembrolizumab in combination with romidepsin to patients with peripheral T-cell lymphoma or cutaneous T-cell lymphoma. Researchers also want to learn if the study drug combination can help to control the disease.

This is an investigational study. Pembrolizumab is FDA approved and commercially available for the treatment of certain types of melanoma. Romidepsin is FDA approved and commercially available for the treatment of peripheral T-cell lymphoma and cutaneous T-cell lymphoma. The use of these drugs in combination with each other is investigational.

The study doctor can explain how pembrolizumab and romidepsin are designed to work.

Pembrolizumab will be provided at no cost to you while you are on study. You and/or your insurance provider will be responsible for the cost of romidepsin.

Up to 33 participants will be enrolled in this study. All will take part at MD Anderson.


Condition or disease Intervention/treatment Phase
Lymphoid Haematopoietic Malignant Neoplasms Cutaneous T-Cell Lymphoma Refractory Cutaneous T-cell Lymphoma Drug: Pembrolizumab Drug: Romidepsin Phase 1 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 39 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Up to 3 groups of up to 6 participants will be enrolled in Phase 1 of the study, and up to 21 participants will be enrolled in Phase 2.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Pembrolizumab (MK-3475) in Combination With Romidepsin in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma
Actual Study Start Date : November 14, 2017
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2021


Arm Intervention/treatment
Experimental: Phase I: Pembrolizumab + Romidepsin Drug: Pembrolizumab
Phase I and II Dose: 200 mg by vein every 3 weeks on Day 1 for up to 36 cycles.
Other Names:
  • Keytruda
  • MK-3475
  • SCH-900475

Drug: Romidepsin

Phase I Starting Dose: 14 mg/m2 by vein on Day 1 and 8 of each 3 week cycle.

Phase II Starting Dose: Maximum tolerated dose from Phase I.

Other Names:
  • Istodax
  • Depsipeptide
  • FK228

Experimental: Phase II: MTD Pembrolizumab + Romidepsin Drug: Romidepsin

Phase I Starting Dose: 14 mg/m2 by vein on Day 1 and 8 of each 3 week cycle.

Phase II Starting Dose: Maximum tolerated dose from Phase I.

Other Names:
  • Istodax
  • Depsipeptide
  • FK228




Primary Outcome Measures :
  1. Dose Limiting Toxicity (DLT) of Pembrolizumab (MK-3475) in Combination With Romidepsin [ Time Frame: 21 days ]
    DLT determined by adverse events recorded according to Common Terminology Criteria for Adverse Events (CTCAE) criteria version 4.0.


Secondary Outcome Measures :
  1. Overall Response (OR) of Pembrolizumab (MK-3475) in Combination With Romidepsin [ Time Frame: After 3, 21 day cycles ]
    OR response defined as number of participants with a complete response (CR) and partial response (PR). Response assessment performed utilizing Lugano Revised Response Criteria.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with peripheral T-cell lymphoma (including but not limited to PTCL-NOS, antioimmunoblastic T-cell lymphoma, anaplastic large T-cell lymphoma). Patients with mycosis fungoides with large cell transformation with measurable disease is eligible.
  2. Disease status defined as refractory to or relapsed after >/=1 prior treatment lines.
  3. 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.
  4. Patients with a measurable disease, defined by a node or mass with the longest diameter >/= 1.5cm
  5. Be willing and able to provide written informed consent/assent for the trial.
  6. Be >/= 18 years of age on day of signing informed consent.
  7. Patients with PTCL should have radiographically measurable disease >/= 1.5cm.
  8. 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 6 weeks (42 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.
  9. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  10. Demonstrate adequate organ function: Absolute neutrophil count (ANC) >/=1,500 /mcL; Platelets >/= 100,000 / mcL; Hemoglobin >/=9 g/dL or >/=5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment); Serum creatinine OR Measured or calculated creatinine clearance Glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl) </= 1.5 X upper limit of normal (ULN) OR >/= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN; Serum total bilirubin </=1.5 X ULN OR Direct bilirubin </=ULN for subjects with total bilirubin levels > 1.5 ULN; AST (SGOT) and ALT (SGPT) </= 2.5 X ULN OR </=5 X ULN for subjects with liver metastases; Albumin >/=2.5 mg/dL;
  11. Continuation 9) International Normalized Ratio (INR) or Prothrombin Time (PT) </=1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or Partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants; Activated Partial </= 1.5 X ULN unless subject is receiving; Thromboplastin Time (aPTT)anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants; a) Creatinine clearance should be calculated per institutional standard.
  12. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  13. Female subjects of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 120 days after the last dose of study medication.
  14. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  15. Male subjects of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

Exclusion Criteria:

  1. Is currently participating and 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.
  2. Has a diagnosis of immunodeficiency, is receiving systemic steroids above physiologic dose (>10mg/day prednisone or equivalent) within 7 days of start of therapy or is receiving any other fomr of immunosuppressive therapy.
  3. Has a known history of active TB (Bacillus Tuberculosis)
  4. Hypersensitivity to pembrolizumab or any of its excipients.
  5. 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.
  6. 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.
  7. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  8. 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.
  9. 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  10. Has known history of non-infectious pneumonitis that required systemic steroid use, or has active pneumonitis.
  11. Has an active infection requiring systemic therapy.
  12. 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.
  13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  14. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  15. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  17. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  18. Baseline electrocardiogram (EKG) shows QTcF > 470 msec
  19. Concomitant use of strong CYP3A4 inhibitors and inducers.
  20. Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
  21. Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years. (Subjects who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of Graft versus Host Disease (GVHD).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03278782


Contacts
Contact: Swaminathan P. Iyer, MD 713-792-2860 spiyer@mdanderson.org

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Clinical Research Operations       spiyer@mdanderson.org   
Sponsors and Collaborators
M.D. Anderson Cancer Center
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Swaminathan P. Iyer, MD UT MD Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03278782     History of Changes
Other Study ID Numbers: 2017-0272
NCI-2018-01051 ( Registry Identifier: NCI CTRP )
First Posted: September 12, 2017    Key Record Dates
Last Update Posted: August 14, 2018
Last Verified: August 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Refractory Peripheral T-Cell Lymphoma
Cutaneous T-cell lymphoma
Pembrolizumab
Keytruda
MK-3475
SCH-900475
Romidepsin
Istodax
Depsipeptide
FK228

Additional relevant MeSH terms:
Lymphoma
Lymphoma, T-Cell
Neoplasms
Lymphoma, T-Cell, Peripheral
Lymphoma, T-Cell, Cutaneous
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Pembrolizumab
Romidepsin
Antineoplastic Agents
Antibiotics, Antineoplastic