Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Lymphoma, T-Cell, Cutaneous

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Peripheral T-cell Lymphoma

Cutaneous T-cell Lymphoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Pembrolizumab

Immunomodulating Agents

Immunoglobulins

Brentuximab Vedotin

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Immunotoxins

Immunoconjugates

Immunologic Factors

All subjects are scheduled to receive up to 16 cycles of combinatorial treatment with brentuximab + pembrolizumab, followed by up to 19 additional cycles of pembrolizumab monotherapy.

After receiving 35 total doses of pembrolizumab (i.e. scheduled for 16 doses in the combinatorial setting and 8 doses as monotherapy), a subject's pembrolizumab treatment will be complete.

Brentuximab vedotin is an antibody-drug conjugate medication used to treat relapsed or refractory Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL), a type of T cell non-Hodgkin lymphoma. It selectively targets tumor cells expressing the CD30 antigen, a defining marker of Hodgkin lymphoma and ALCL.

Brentuximab vedotin

Pembrolizumab is a humanized antibody used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cervical cancer, and certain types of breast cancer.

Maxime Oriol, BS

Julie Holub

Kylie Boyhen

Tarsheen Sethi, MD

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 \~65%. Pembrolizumab and brentuximab will be administered for 16 cycles in patients with responsive disease. Pembrolizumab will be continued for an additional 19 cycles (total 35 cycles). Response assessments will occur at pre-specified intervals. Dose adjustments for specific toxicities with either drugs are detailed in the protocol. Based on statistical analysis 43 subjects will need to be accrued to evaluate for disease response based on historical control.

CD30- Positive Peripheral T cell (PTCL) and Cutaneous T cell Lymphomas (CTCL):

T-cell Non-Hodgkin Lymphoma (NHL) includes a clinically heterogeneous group of mature T-cell lymphomas accounting for 10-12% of all NHL. Peripheral T- cell Lymphoma (PTCL) present with clinically aggressive disease with a poor outcome \[with the exception of ALK+ Anaplastic Large Cell Lymphomas (ALCL)\] and patients experience a high incidence of relapsed/ refractory disease that poses a therapeutic challenge.

Despite progress in the past decade in understanding the biology of T-cell lymphomas, with the use of next generation sequencing and molecular profiling of archived tissue samples, there is yet an unmet need in therapeutic options. Amidst the wide range of T-cell lymphoma histologies, PTCL NOS is the most common histological subtype followed by ALCL, angioimmunoblastic lymphoma (AITL) and cutaneous T-cell lymphoma (CTCL). The other histological subtypes (Enteropathy associated T-cell Lymphoma, hepatosplenic T cell lymphoma, NK/T cell lymphoma etc.) account for \<5% of T-cell subtypes. Unfortunately, the rare subtypes of T-cell Lymphoma are usually excluded from later phase trials due to their dismal prognosis.

Therapeutic Challenge in Relapsed/ Refractory PTCL and CTCL:

For patients with disease relapse following upfront chemotherapy, stem cell transplantation (SCT) is an option. However, this type of aggressive approach is only feasible in a minority of patients. Despite the advances in the therapeutic arsenal, most of these agents have a modest response rate of 20-30%. More than half of these patients who do respond initially, will ultimately relapse. Conventional chemotherapy in combination with novel agents has been under clinical evaluation with minor improvements in response rates compared with historical controls. Therefore, the urge to optimize therapy by incorporating newer treatments such as novel agents that have a more targeted approach continues to be critically important.

CTCL presents as a chronic disease with a poor prognosis in advanced stage disease. While recently approved agents have expanded the treatment repertoire for CTCL, there is still a need for additional agents as median response with current options averaging about a year(1).

In this context, the efficacy of the novel combination of CD30 directed antibody Brentuximab and PD-1 inhibitor Pembrolizumab in PTCL and CTCL is not known.

All subjects are scheduled to receive up to 16 cycles of combinatorial treatment with brentuximab + pembrolizumab, followed by up to 19 additional cycles of pembrolizumab monotherapy

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

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

As assessed by the Lugano criteria for PTCL(16) and the global response score for CTCL(17)

As assessed by using the NCI Common Terminology Criteria for Adverse Events version 5 (CTCAE v5) for grading

Defined as the time from enrollment to earliest of progression, death or follow-up

Defined as the time from enrollment to death or last follow-up

Defined as interval from initiation of chemotherapy to premature discontinuation for any reason.

Defined as the interval from response initiation (when either CR or PR is first determined) to progression or death, whichever occurs first.

Defined as the time from treatment initiation to tumor progression.

Merck Sharp & Dohme LLC

Sethi

MD, MSCI, Assistant Professor of Medicine

Symptoms and General Pathology

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Leukemia

Leukemia, B-Cell

Leukemia, Lymphoid

Hematologic Diseases

Chronic Disease

Disease Attributes

Chronic Lymphocytic Leukemia

Follicular Lymphoma

B-cell Lymphoma

Marginal Zone Lymphoma

Diffuse Large B-Cell Lymphoma

Gray Zone Lymphoma

Chronic Graft Versus Host Disease

Antirheumatic Agents

Bendamustine Hydrochloride

Rituximab

Antineoplastic Agents, Alkylating

Alkylating Agents

Brentuximab Vedotin in Combination with Bendamustine and Rituximab

Brentuximab vedotin IV over 30 minutes on day 1.Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Brentuximab

Bendamustine IV over 30-60 minutes on days 1-2. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Bendamustine

Rituximab IV on day 2. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Daniel O. Persky, MD

This phase II trial studies how well brentuximab vedotin, bendamustine, and rituximab work in treating patients with B-cell non-Hodgkin lymphoma that has returned after a period of improvement or has not responded to previous treatment. Monoclonal antibody-drug conjugates, such as brentuximab vedotin, use antibody to target chemotherapy in cancer cells. Drugs used in chemotherapy, such as bendamustine, work in different ways to kill cancer cells. Monoclonal antibodies, such as rituximab, kill the cancer cells directly, but also harness the immune system to kill the cancer cells. Adding brentuximab to rituximab may improve response rates in CD30 positive, CD20 positive Relapsed Refactory NHL.

PRIMARY OBJECTIVES:

I. Complete response (CR) rate and overall response rate (ORR) for patients with relapsed aggressive high-risk non-Hodgkin lymphoma (NHL) treated with brentuximab vedotin, bendamustine and rituximab (S-BR).

SECONDARY OBJECTIVES:

I. To estimate 2-year progression-free survival (PFS). II. To evaluate rate of positron emission tomography (PET)-CR and correlation to 2 year PFS.

III. To evaluate the toxicity of six cycles of S-BR. IV. To evaluate mobilization, stem cell collection, engraftment in patients that proceed to salvage autologous stem cell transplant (ASCT).

SCIENTIFIC OBJECTIVES:

I. To evaluate percentage of tumor cells that are positive or negative for cluster of differentiation (CD)30 by immunohistochemistry (IHC), the subcellular location of CD30 (membrane or cytoplasmic only with absence of membrane expression), intensity of scoring, and correlating with clinical outcomes.

II. To evaluate gene expression profiling (GEP) by Nanostring Technology and comparing expression levels of target genes in CD30 membrane positive, CD30 cytoplasmic only positive or CD30 negative tumor cells.

III. To evaluate correlation between mutations identified through next generation sequencing (NGS) including ribonucleic acid (RNA) sequencing of the tumor transcriptome, and correlating to GEP and CD30 IHC, and correlating to clinical outcomes.

IV. To evaluate the levels of soluble CD30 at baseline and in response to treatment.

SCHEDULE:

Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1, bendamustine IV over 30-60 minutes on days 1-2, and rituximab IV on day 2. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years.

Brentuximab Vedotin, Bendamustine, and Rituximab in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

Phase II Study of Brentuximab Vedotin in Combination With Bendamustine and Rituximab, in Patients With CD30 Positive, Relapsed or Refractory B Cell Non-Hodgkin Lymphoma (NHL)

Subcellular location or CD30 (membrane or cytoplasmic only), intensity of scoring, and association with progression-free survival will be evaluated. These relationships will be assessed using a Cox proportional hazards model. Expression levels of target genes based on CD30 location will be assessed using two sample independent t tests, with adjustment for multiple comparisons to protect the false discovery rate.

The relationship between mutations identified through next generation sequencing, gene expression profiling, CD30 IHC and progression-free survival will be assessed using a Cox proportional hazards models.

The complete response rate will be estimated as the proportion of patients with response, with a 95% exact confidence interval.

The overall response rate will be estimated as the proportion of patients with response, with a 95% exact confidence interval.

PFS will be estimated using the Kaplan-Meier estimate, with stratification by allogeneic stem cell transplantation status.

The complete response rate by PET/CT will be estimated with the 95% exact confidence interval.

The proportion of patients with treatment-emergent AEs will be tabulated, including by causality, seriousness, severity/grade, and whether the AE resulted in death or discontinuation of treatment.

Brentuximab vedotin pharmacokinetics in combination therapy will be measured and correlated to single agent data.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pembrolizumab and Brentuximab Vedotin in Subjects With Relapsed/Refractory T-cell Lymphoma	NCT05313243	T-Cell Lymphoma	Brentuximab ved... Pembrolizumab	18 Years -	Yale University
Brentuximab Vedotin, Bendamustine, and Rituximab in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma	NCT02623920	Diffuse Large B... Mediastinal Lar... Grey Zone Lymph... High Grade B Ce... Follicular Lymp... Marginal Zone L... Small Lymphocyt...	Brentuximab Bendamustine Rituximab	18 Years -	University of Arizona
Pembrolizumab and Brentuximab Vedotin in Subjects With Relapsed/Refractory T-cell Lymphoma	NCT05313243	T-Cell Lymphoma	Brentuximab ved... Pembrolizumab	18 Years -	Yale University

Spots Global Cancer Trial Database for brentuximab

Every month we try and update this database with for brentuximab cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for brentuximab

Every month we try and update this database with for brentuximab cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for brentuximab cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.