Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Follicular

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Composite Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Follicular Lymphoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

All Drugs and Chemicals

Antineoplastic Agents

Antirheumatic Agents

Anti-Inflammatory Agents

Anti-Infective Agents

Antibodies

Antibodies, Monoclonal

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Pembrolizumab

Prednisone

Rituximab

Vincristine

Immunoglobulins

Cortisone

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Immune Checkpoint Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Tubulin Modulators

Antimitotic Agents

Patients receive pembrolizumab IV over 30 minutes on day 1 and prednisone PO on days 1-5. Patients also receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 2 of course 1 and on day 1 of subsequent courses. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Doxorubicin Hydrochloride

Laboratory Biomarker Analysis

Vincristine Sulfate

Stephen Smith

This pilot phase I trial studies the side effects of pembrolizumab and combination chemotherapy in treating patients with previously untreated diffuse large B-cell lymphoma or grade 3b follicular lymphoma. Monoclonal antibodies, such as pembrolizumab and rituximab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pembrolizumab together with combination chemotherapy may be with a better treatment for diffuse large B-cell lymphoma or follicular lymphoma.

PRIMARY OBJECTIVES:

I. To measure the toxicity profile of pembrolizumab (MK-3475) when co-administered with full-course RCHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone) in subjects with previously untreated diffuse large B-cell lymphoma (DLBCL).

SECONDARY OBJECTIVES:

I. To assess clinical outcomes including response rate, event-free survival, and overall survival after MK-3475 + RCHOP induction for subjects with previously untreated DLBCL.

TERTIARY OBJECTIVES:

I. To measure baseline expression of proteins in the programmed death-1 (PD-1) family on tumor cells and coexisting immune infiltrates, using archival tissue when available.

II. To measure peripheral blood T cell subsets before and after treatment using flow cytometry, and to measure baseline vitamin D (25-hydroxy, total).

III. To explore relationships with these parameters and likelihood of response to therapy and outcomes.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and prednisone orally (PO) on days 1-5. Patients also receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 2 of course 1 and on day 1 of subsequent courses. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of the study treatment, patients are followed up to 5 years.

Pembrolizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Diffuse Large B-cell Lymphoma or Grade 3b Follicular Lymphoma

MK-3475 in Combination With Standard RCHOP Therapy for Previously Untreated Diffuse Large B-Cell Lymphoma

Tissue-based assays for tumor and immune infiltrate will be conducted centrally when archival tissue is available. These analyses will seek to identify alterations in T-cell subsets for comparison with historical studies, and exploration of association with treatment outcomes achieved with study therapy.

The Primary Outcome measures toxicity, with particular attention to Events of Clinical Interest when adding MK-3475 to standard RCHOP therapy. The sample size of 30 patients will permit the estimation of a 40% incidence of grade 3-5 clinically relevant toxicity.

Statistical analysis will entail descriptive statistics, and survival analysis including Kaplan-Meier estimates, log-rank testing of univariate prognostic factors, Cox proportional hazards analysis, as well as T-testing and regression analysis for comparing continuous variables in correlative study data.

Tumor imaging at baseline and 4-6 weeks, +/-7 days, after 6 courses of induction therapy with MK-3475 + RCHOP to determine remission status. Response will be measured according to 2014 Criteria ("The Lugano Classification").

National Cancer Institute (NCI)

University of Washington

Patients will receive pembrolizumab IV over 30 minutes on day 1 and prednisone PO on days 1-5. Patients also receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 2 of course 1 and on day 1 of subsequent courses. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Cyclophosphamide: Given IV

Doxorubicin Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pembrolizumab: Given IV

Prednisone: Given PO

Rituximab: Given IV

Vincristine Sulfate: Given IV

Treatment (Pembrolizumab, Combination Chemotherapy)

Patients receive pembrolizumab IV over 30 minutes on day 1 and prednisone PO on days 1-5. Patients also receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 2 of course 1 and on day 1 of subsequent courses. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Cyclophosphamide: Given IV

Doxorubicin Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pembrolizumab: Given IV

Prednisone: Given PO

Rituximab: Given IV

Vincristine Sulfate: Given IV

Age, Categorical

Age, Continuous

Sex: Female, Male

Race

Race/Ethnicity, Customized

United States

Region of Enrollment

Dr. Stephen Smith

Number of Participants With a Grade 3 or Higher Toxicity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

Treatment-related Mortality

Event-free Survival

Overall Survival

Response Rate Measured by Tumor Imaging

Changes in T-cell Subsets

Overall Study

Symptoms and General Pathology

Behaviors and Mental Disorders

Nervous System Diseases

Syndrome

Lymphoma, Mantle-Cell

Lymphoma, B-Cell, Marginal Zone

Aggression

Dementia

Aberrant Motor Behavior in Dementia

Behavioral Symptoms

Mantle Cell Lymphoma

Marginal Zone Lymphoma

Richter Syndrome

Lenalidomide

Angiogenesis Inhibitors

Growth Inhibitors

Patients receive ALX148 IV over 1 hour once on days 1, 8, 15 and 22, or days 1 and 15, or day 1 depending on dose level. Patients also receive rituximab IV over 4-6 hours on days 1, 8, 15 and 22 of cycle 1, then on day 1 of cycles 2-6, and lenalidomide PO QD on days 1-21 of cycles 1-6. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

CD47 Antagonist ALX148

Paolo Strati, MD

Paolo Strati

This phase I/II trial finds out the best dose, possible benefits and/or side effects of ALX148 in combination with rituximab and lenalidomide in treating patients with indolent and aggressive B-cell non-Hodgkin lymphoma. Immunotherapy with ALX148, may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs, such as lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Rituximab is a monoclonal antibody that binds to a protein called CD20 found on B-cells, and may kill cancer cells. Giving ALX148 in combination with rituximab and lenalidomide may help to control the disease.

PRIMARY OBJECTIVES:

I. To evaluate safety and tolerability, and to determine the recommended phase II dose (RP2D) and schedule of CD47 antagonist ALX148 (ALX148) in combination with rituximab and lenalidomide in patients with relapsed or refractory B-non-Hodgkin lymphomas (NHLs) (both indolent and aggressive histology) in phase I.

II. To evaluate the efficacy of the combination of ALX148, rituximab and lenalidomide at the RP2D (determined in phase I) in patients with previously untreated and high tumor burden indolent B-NHL in phase II.

SECONDARY OBJECTIVE:

I. To evaluate other toxicity and efficacy measures of the combination of ALX148, rituximab and lenalidomide.

EXPLORATORY OBJECTIVE:

I. To determine the pharmacodynamic effects and investigate biomarkers of response and resistance.

OUTLINE: This is a phase I, dose-escalation study of ALX148 followed by a phase II study.

Patients receive ALX148 intravenously (IV) over 1 hour once on days 1, 8, 15 and 22, or days 1 and 15, or day 1 depending on dose level. Patients also receive rituximab IV over 4-6 hours on days 1, 8, 15 and 22 of cycle 1, then on day 1 of cycles 2-6, and lenalidomide orally (PO) daily once (QD) on days 1-21 of cycles 1-6. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 7 and 30 days, then up to 3 years.

ALX148, Rituximab and Lenalidomide for the Treatment of Indolent and Aggressive B-cell Non-Hodgkin Lymphoma

A Phase I/II Open Label, Single Center, Study of the Combination of ALX148, Rituximab and Lenalidomide in Patients With Indolent and Aggressive B-Cell Non-Hodgkin Lymphoma

Response will be assessed by the investigator based on the 2014 Cheson Lugano criteria. The number and percentage of subjects with a CR at the end of treatment will be tabulated. The CR rate will be estimated with its exact 95% confidence interval (CI).

Will be assessed by the investigator based on Cheson, Lugano 2014. The number and percentage of subjects with an ORR will be tabulated. The best ORR will be recorded and summarized using exact method for 95% CI.

Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.

Safety summaries will include tabulations in the form of tables and listings. The frequency (number and percentage) of treatment-emergent AEs will be reported. Additional AE summaries will include AE frequency by AE severity and by relationship to study drug. Clinically significant abnormal laboratory values will be summarized.

M.D. Anderson Cancer Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Pembrolizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Diffuse Large B-cell Lymphoma or Grade 3b Follicular Lymphoma	NCT02541565	Composite Lymph... Grade 3b Follic... Stage I Diffuse... Stage I Follicu... Stage II Diffus... Stage II Follic... Stage III Diffu... Stage III Folli... Stage IV Diffus... Stage IV Follic...	Cyclophosphamid... Doxorubicin Hyd... Laboratory Biom... Pembrolizumab Prednisone Rituximab Vincristine Sul...	18 Years -	University of Washington
ALX148, Rituximab and Lenalidomide for the Treatment of Indolent and Aggressive B-cell Non-Hodgkin Lymphoma	NCT05025800	Aggressive B-Ce... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Composite Lymph... Indolent B-Cell... Refractory Aggr... Refractory Foll... Refractory Grad... Refractory High... Refractory Mant... Refractory Marg... Refractory Prim... Refractory Tran... Refractory Tran... Richter Syndrom...	CD47 Antagonist... Lenalidomide Rituximab	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for composite lymphoma