RECRUITING

Pembrolizumab and Brentuximab Vedotin in Subjects with Relapsed/Refractory T-cell Lymphoma

Conditions

T-Cell Lymphoma Relapsed Refractory CD30 positive Peripheral T-cell lymphoma Cutaneous T-cell lymphoma Pembrolizumab Brentuximab

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a single arm, open label, multicenter study phase 2 study of pembrolizumab and brentuximab in subjects with relapsed/refractory CD30 positive T-cell lymphoma (including peripheral T-cell lymphoma and cutaneous T-cell lymphoma) who have received at least one prior therapy. We hypothesize that this combination is effective and will produce an overall response rate of \~55%. Pembrolizumab and brentuximab will be administered for 16 cycles in subjects with responsive disease. Pembrolizumab will be continued for an additional 19 cycles (total 35 cycles). Response assessments will occur at pre-specified intervals. For the primary endpoint the response assessment after 3 cycles will be taken into consideration. Dose adjustments for specific toxicities with either drug are detailed in the protocol. Based on statistical analysis 32 subjects will need to be accrued to evaluate for disease response based on historical control.

Official Title

Phase 2 Study of Pembrolizumab and Brentuximab Vedotin in Subjects with Relapsed/Refractory CD30 Positive T-cell Lymphoma

Quick Facts

Study Start:2023-07-10

Study Completion:2028-07-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05313243

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of T-cell Non-Hodgkin lymphoma (T-NHL) will be enrolled in this study. 2. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 4. Histologically confirmed T-cell Non-Hodgkin lymphoma (T-NHL), including: * Peripheral T-cell lymphoma not other specified (PTCL nos) * Angioimmunoblastic T-cell lymphoma (AITL) * Anaplastic large-cell lymphoma (ALCL) * Natural killer (NK)/T-cell lymphoma (nodal or extranodal) * Cutaneous T-cell lymphoma (CTCL), including mycosis fungoides (MF)/sezary syndrome * Transformed T-cell lymphoma * Enteropathy-associated T-cell lymphoma (EATL); * Subcutaneous panniculitis-like T-cell lymphoma (SCPTCL) * Hepatosplenic T- cell lymphomas. 5. Presence of CD30 (\>1%) by IHC on a previous biopsy sample 6. Relapsed/refractory disease having failed at least one prior systemic therapy Note: Single agent Brentuximab could have been a prior line of therapy EXCEPT those with ≥ grade 2 side effects leading to treatment discontinuation or those refractory to Brentuximab 7. For patients with peripheral T-cell lymphoma (PTCL): At least one measurable target lesion ≥1.5 cm 8. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: * Not a woman of childbearing potential (WOCBP) * A woman of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test during screening within 72 hours prior to receiving first dose of protocol-indicated treatment, and must agree to follow instructions for using acceptable contraception from the time of signing consent, and at least 120 days (4 months) after her final dose of pembrolizumab. 9. A male participant must agree to use contraception during the treatment period and for at least at least 120 days (4 months) after the final dose of pembrolizumab. and refrain from donating sperm during this period. 10. Adequate organ and bone marrow function resulted ≤ 10 days prior to first dose of protocol-indicated treatment:	1. Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137). 2. Patients with adult T-cell leukemia/ lymphoma (ATLL) 3. Has received prior systemic anti-cancer therapy including investigational agents ≤ 4 weeks prior to first dose of study treatment on Cycle 1, Day 1. Could consider shorter interval for kinase inhibitors or other short half-life drugs. 4. Pregnant or breast-feeding females. A WOCBP who has a positive urine pregnancy test at screening. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. In the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication. 5. Has received radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease. 6. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. 7. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed. 8. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. 9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. 10. Has active autoimmune disease that has required systemic treatment in the past one year (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). 11. Active uncontrolled infection requiring systemic therapy (patients must be afebrile for ≥ 48 hours off antibiotics prior to first protocol treatment). If fever is attributed to tumor fever (B symptom) then this criteria would not apply. 12. Active myocarditis, regardless of etiology; or New York Heart Association (NYHA) functional classification III-IV heart failure. 13. Known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment. 14. Disease free of prior malignancies for ≥ 1 year with exception of currently treated basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast. (Other malignancies will require advance discussion and agreement between the investigator and the sponsor-investigator regarding risk of recurrence.) 15. Known severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients. 16. Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority. 17. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority. 18. Has a history or current evidence of any condition (e.g. renal disease that would preclude treatment or obstructive pulmonary disease and history of bronchospasm), therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 19. Clinically significant history of liver disease, including current alcohol abuse or cirrhosis. 20. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 21. Has a known history of active TB (Bacillus Tuberculosis). 22. Prior allogeneic stem cell transplant within last 5 years or active graft vs. host disease (GVHD). 23. Patients with grade 2 or higher peripheral neuropathy

Inclusion Criteria

Exclusion Criteria

1. Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of T-cell Non-Hodgkin lymphoma (T-NHL) will be enrolled in this study.
2. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
4. Histologically confirmed T-cell Non-Hodgkin lymphoma (T-NHL), including:
* Peripheral T-cell lymphoma not other specified (PTCL nos)
* Angioimmunoblastic T-cell lymphoma (AITL)
* Anaplastic large-cell lymphoma (ALCL)
* Natural killer (NK)/T-cell lymphoma (nodal or extranodal)
* Cutaneous T-cell lymphoma (CTCL), including mycosis fungoides (MF)/sezary syndrome
* Transformed T-cell lymphoma
* Enteropathy-associated T-cell lymphoma (EATL);
* Subcutaneous panniculitis-like T-cell lymphoma (SCPTCL)
* Hepatosplenic T- cell lymphomas.
5. Presence of CD30 (\>1%) by IHC on a previous biopsy sample
6. Relapsed/refractory disease having failed at least one prior systemic therapy Note: Single agent Brentuximab could have been a prior line of therapy EXCEPT those with ≥ grade 2 side effects leading to treatment discontinuation or those refractory to Brentuximab
7. For patients with peripheral T-cell lymphoma (PTCL): At least one measurable target lesion ≥1.5 cm
8. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
* Not a woman of childbearing potential (WOCBP)
* A woman of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test during screening within 72 hours prior to receiving first dose of protocol-indicated treatment, and must agree to follow instructions for using acceptable contraception from the time of signing consent, and at least 120 days (4 months) after her final dose of pembrolizumab.
9. A male participant must agree to use contraception during the treatment period and for at least at least 120 days (4 months) after the final dose of pembrolizumab. and refrain from donating sperm during this period.
10. Adequate organ and bone marrow function resulted ≤ 10 days prior to first dose of protocol-indicated treatment:

1. Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
2. Patients with adult T-cell leukemia/ lymphoma (ATLL)
3. Has received prior systemic anti-cancer therapy including investigational agents ≤ 4 weeks prior to first dose of study treatment on Cycle 1, Day 1. Could consider shorter interval for kinase inhibitors or other short half-life drugs.
4. Pregnant or breast-feeding females. A WOCBP who has a positive urine pregnancy test at screening. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. In the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
5. Has received radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
6. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
7. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
8. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
10. Has active autoimmune disease that has required systemic treatment in the past one year (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
11. Active uncontrolled infection requiring systemic therapy (patients must be afebrile for ≥ 48 hours off antibiotics prior to first protocol treatment). If fever is attributed to tumor fever (B symptom) then this criteria would not apply.
12. Active myocarditis, regardless of etiology; or New York Heart Association (NYHA) functional classification III-IV heart failure.
13. Known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
14. Disease free of prior malignancies for ≥ 1 year with exception of currently treated basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast. (Other malignancies will require advance discussion and agreement between the investigator and the sponsor-investigator regarding risk of recurrence.)
15. Known severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
16. Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority.
17. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
18. Has a history or current evidence of any condition (e.g. renal disease that would preclude treatment or obstructive pulmonary disease and history of bronchospasm), therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
19. Clinically significant history of liver disease, including current alcohol abuse or cirrhosis.
20. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
21. Has a known history of active TB (Bacillus Tuberculosis).
22. Prior allogeneic stem cell transplant within last 5 years or active graft vs. host disease (GVHD).
23. Patients with grade 2 or higher peripheral neuropathy

Contacts and Locations

Study Contact

Stephanie Ladd, BS

CONTACT

954-895-0576

stephanie.ladd@yale.edu

Julie Holub

CONTACT

Julie.holub@yale.edu

Principal Investigator

Tarsheen Sethi, MD

PRINCIPAL_INVESTIGATOR

Yale University

Study Locations (Sites)

Yale Smilow Cancer Hospital

New Haven, Connecticut, 06510

United States

Dana Farber Cancer Institute

Boston, Massachusetts, 02115

United States

Collaborators and Investigators

Sponsor: Yale University

Tarsheen Sethi, MD, PRINCIPAL_INVESTIGATOR, Yale University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-07-10

Study Completion Date2028-07-30

Study Record Updates

Study Start Date2023-07-10

Study Completion Date2028-07-30

Terms related to this study

Keywords Provided by Researchers

Relapsed
Refractory
CD30 positive
Peripheral T-cell lymphoma
Cutaneous T-cell lymphoma
Pembrolizumab
Brentuximab

Additional Relevant MeSH Terms

T-Cell Lymphoma