Symptoms and General Pathology

All Conditions

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Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Recurrence

Lymphoma

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Disease Attributes

Lymphosarcoma

Mantle Cell Lymphoma

Follicular Lymphoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

All Drugs and Chemicals

Immunomodulating Agents

Administrated with IL-2 programmed CD19.CAR-T cells on day 0,1,2 in the lympho-depleted patients

Administrated with IL-7/IL-15 programmed CD19.CAR-T cells on day 0,1,2 in the lympho-depleted patients

Retroviral vector-transduced autologous T cells to express CD19-specific CARs

CD19.CAR-T cells

Qingzhu Jia, M.D.

Qingzhu Jia, MD

Bo Zhu, M.D., Ph.D.

The goal of this clinical trial is to study how approaches for manufacturing chimeric antigen receptor (CAR)-modified T (CAR-T) cells affect their in vivo persistence and therapeutic efficacy against B lymphoma. Recently, cancer immunotherapy, treatments aiming to arm patients with immunity specifically against cancer cells, has emerged as a promising therapeutic strategy. Among the many emerging immunotherapeutic approaches, clinical trials utilizing CARs against B cell malignancies have demonstrated remarkable potential. CARs combine the variable region of an antibody with T-cell signaling moieties to confer T-cell activation with the targeting specificity of an antibody. Thus, CARs are not MHC-restricted so they are not vulnerable to MHC down regulation by tumors. However, defined by the activation and contraction program of their mother cells, the persistency and function of CAR-T cells are also restricted by the protocol of manufacturing. Previous clinical studies largely utilized interleukin-2 (IL-2) for the ex vivo expansion of CAR-T cells, which preferentially generate CAR-T cells with characteristics of terminally differentiated effector cells. Our preliminary data indicated that two common gamma chain cytokines, IL-7 and IL-15, can help to selectively expand CAR-T cells with various memory phenotypes. CAR-T Cells prepared under this condition resulted in improved therapeutic efficacy in preclinical animal models. This clinical investigation is to test a hypothesis whether IL-7/IL-15-programmed anti-CD19 CAR-T cells persist longer in lymphoma patients after infusion and whether the persistency of CAR-T cells can lead to improved anti-lymphoma efficacy.

Primary Objectives

1. To determine the safety and feasibility of CD19.CAR-T cells manufactured through IL-7/IL-15-mediated expansion or IL-2-mediated expansion
2. To determine in vivo dynamics and persistency of IL-7/IL-15 programmed CD19.CAR-T cells.
3. To determine the efficacy of IL-7/IL-15 programmed CD19.CAR-T cells in treating patients with CD19-positive lymphoma

Secondary Objectives

1. To determine whether the IL-7/IL-15 programmed CD19.CAR-T cells are superior to the IL-2 programmed cells as measured by their in vivo persistence post infusion
2. To determine whether the IL-7/IL-15 programmed CD19.CAR-T cells are superior to the IL-2 programmed cells as measured by their efficacy in lymphoma therapy
3. To assess the dynamics of intratumoral infiltration of CD19.CAR-T cells.
4. To correlate the subsets and differentiation of CD19.CAR-T cells to observed anti-tumor efficacy

Memory-enriched CAR-T Cells Immunotherapy for B Cell Lymphoma

A Two-Arm, Single-Center, Open-Label Pilot Study of IL-2 Programmed or IL-7/IL-15 Programmed Anti-CD19:TCRz:CD28 T-cells in Patient With CD19-Positive Lymphoma That is Resistant or Refractory to Chemotherapy

Xuzhou Medical University

Hrain Biotechnology Co., Ltd.

Shanghai Changzheng Hospital

Xinqiao Hospital of Chongqing

Director of Department of Cancer

Composite Lymphoma

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

Infections

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Communicable Diseases

Lymphoma, T-Cell

Acquired Immunodeficiency Syndrome

HIV Infections

Immunologic Deficiency Syndromes

Hodgkin Disease

Virus Diseases

Burkitt Lymphoma

Plasmablastic Lymphoma

Lymphoma, Large-Cell, Immunoblastic

Epstein-Barr Virus Infections

Herpesviridae Infections

DNA Virus Infections

Tumor Virus Infections

Hodgkin Lymphoma

Lymphoma, Large-cell, Immunoblastic

Dermatologic Agents

Amino Acids

Etoposide

Cytarabine

Melphalan

Etoposide phosphate

Podophyllotoxin

Carmustine

Mechlorethamine

Nitrogen Mustard Compounds

Antimetabolites

Antiviral Agents

Keratolytic Agents

Phenylalanine

Alanine

Patients receive BEAM regimen administered as standard of care comprising carmustine on day -6, cytarabine BID on days -5 to -2, etoposide BID on days -5 to -2, and melphalan on day -1. Patients undergo infusion of lentivirus vector CCR5 shRNA/TRIM5alpha/TAR decoy-transduced autologous CD34-positive hematopoietic progenitor cells over 1 hour.

Undergo infusion of lentivirus vector CCR5 shRNA/TRIM5alpha/TAR decoy-transduced autologous CD34-positive hematopoietic progenitor cells

Autologous Hematopoietic Stem Cell Transplantation

300 mg/m2 on Day -6, as part of BEAM and R-BEAM regimens.

100 mg/m2 BID on Days -5 through -2, as part of BEAM and R-BEAM regimens.

VP-16: 100 mg/m2 BID on Days -5 through -2, as part of BEAM and R-BEAM regimens.

Lentivirus Vector CCR5 shRNA/TRIM5alpha/TAR Decoy-transduced Autologous CD34-positive Hematopoietic Progenitor Cells

140 mg/m2 on Day -1, as part of BEAM and R-BEAM regimens.

Peripheral Blood Stem Cell Transplantation

Mehrdad Abedi

This phase I/II trial studies the side effects and best dose of gene therapy in treating patients with human immunodeficiency virus (HIV)-related lymphoma that did not respond to therapy or came back after an original response receiving stem cell transplant. In gene therapy, small stretches of deoxyribonucleic acid (DNA) called "anti-HIV genes" are introduced into the stem cells in the laboratory to make the gene therapy product used in this study. The type of anti-HIV genes and therapy in this study may make the patient's immune cells more resistant to HIV-1 and prevent new immune cells from getting infected with HIV-1.

PRIMARY OBJECTIVE:

I. Safety, defined as timely engraftment (the collective establishment of a persistent absolute neutrophil count of at least 500 cells/mm\^3 and platelet count of 20,000 cells/mm\^3 without transfusion for 3 consecutive measurements of laboratory values obtained on different days) by one month post-transplant, in the absence of any grade 3 and 4 non-hematopoietic organ toxicity that can be attributed (possibly, probably, or definitely) to lentiviral transduced stem cell transplant, excluding alopecia, or any clonal expansion and excluding expected toxicities that are associated with the pre-transplant conditioning regimen.

SECONDARY OBJECTIVES:

I. To determine efficacy of the candidate product, defined as establishment of \> 5% mononuclear blood cells expressing anti-HIV genes in the peripheral blood at 3 months post-transplant.

II. To determine the presence, quantity, and duration of gene modified HIV-1 resistant peripheral blood cells and gut mucosal immune cells.

III. To study the integration sites of vector sequences in circulating cells. IV. To study progression-free survival. V. To study overall survival. VI. To study complete response rate and duration. VII. To study partial response rate and duration. VIII. To study time to neutrophil engraftment (first measurement of 3 consecutive laboratory values on different days) of absolute neutrophil count \[ANC\] \>= 500 cells/mm\^3).

IX. To study time to platelet engraftment (first measurement of 3 consecutive measurements laboratory values obtained on different days) of platelets \>= 20,000 cells/mm\^3 without platelet transfusions 7 days prior).

X. To study hematologic function at day 100 (ANC \> 1500, hemoglobin \[Hb\] \> 10 g/dl without transfusion and platelets \> 100,000) XI. To study CD4 recovery at the conclusion of the trial. XII. To study safety in terms of toxicities, infections, transfusions, and infusion-related reactions.

XIII. To study HIV-1 viral load over time. XIV. To study persistence of vector-transduced cells over time.

EXPLORATORY OBJECTIVE:

I. To evaluate the presence and the magnitude of expansion of HIV-1 resistant immune cells in the peripheral blood and gut mucosa of transplanted participants, subsequent to withholding anti-retroviral therapy (ART).

OUTLINE: This is a dose-escalation study of lentivirus vector CCR5 shRNA/TRIM5alpha/TAR decoy-transduced autologous CD34-positive hematopoietic progenitor cells.

Patients receive BEAM or BEAM-R regimen administered as standard of care comprising carmustine on day -6, cytarabine twice daily (BID) on days -5 to -2, etoposide BID on days -5 to -2, and melphalan on day -1. Patients with B-cell lymphoma also receive rituximab on day -6 before chemotherapy and on days 21 and 28 post-transplant as standard of care. Patients undergo intravenous (IV) infusion of lentivirus vector CCR5 shRNA/TRIM5alpha/TAR decoy-transduced autologous CD34-positive hematopoietic progenitor cells over 1 hour.

After completion of study treatment, patients are followed up at days 7, 14, 21, 28, 42, 60, 90, 120, 180, 240, 300, 360, 420, 480, 520, 600, 660, and 720, and then yearly for at least 15 years.

Gene Therapy in Treating Patients With Human Immunodeficiency Virus-Related Lymphoma Receiving Stem Cell Transplant

A Phase I Study of Stem Cell Gene Therapy for HIV Mediated by Lentivector Transduced, Pre-Selected CD34+ Cells

Presence and the magnitude of expansion of HIV-1 resistant immune cells in the peripheral blood and gut mucosa of transplanted participants, subsequent to withholding ART

Timely engraftment is defined as a persistent an absolute neutrophil count (ANC) of at least 500 cells/mm3 and a platelet count of at least 20,000 cells/mm3 for at least 3 days

To determine efficacy of the candidate product, defined as establishment of \> 5% mononuclear blood cells expressing anti-HIV genes

To determine the presence, quantity, and duration of gene modified HIV-1 resistant peripheral blood cells and gut mucosal immune cells

Summarized descriptively. Continuous measures will be summarized by mean (standard deviation \[SD\]) and median (range), with log transformation if necessary for skewed measures, as would be typical for cell counts.

Single genome sequencing of HIV gp120 and HIV pol will be performed to understand sequence evolution following transplantation and detection of minority resistance variants.

Time-to-event data will be presented graphically by Kaplan-Meier plots and summarized by estimated median time to event (if that is estimable from the data) with 95% confidence interval.

The length of time from the start of treatment until death

A complete response is the complete disappearance of any disease, as determined by imaging

Complete response is defined as the absence of any disease on imaging or by exam; progressive disease is defined as new lesions or new evidence of disease

Will be assessed following the Lugano Classification. In the absence of evident disease progression, response will be assessed formally at 3, 6, 12 and 24 months post transplant per study calendar.

First measurement of 3 consecutive laboratory values obtained on different days) of ANC \> 500 cells/mm3

.

First measurement of 3 consecutive laboratory values obtained on different days) of platelets \> 20,000 cells/mm3 without platelet transfusions 7 days prior

At six months post-transplant, or later, ART will be voluntarily withheld for a 12 week period only for participants who have a CD4 count of 300 or higher with no detectable viral load. for participants in which the CD4 T-cell count has not risen to ≥ 300 cells/mm3 at the time of the planned ART interruption, ART will continue until the T-cell count has risen to ≥ 300 cells/mm3.

To study safety in terms of the frequency of toxicities, infections, transfusions, and infusion-related reactions

Vector stability analysis will be performed via qPRC sequencing.

California Institute for Regenerative Medicine (CIRM)

AIDS Malignancy Consortium

Patients receive BEAM regimen administered as standard of care comprising carmustine on day -6, cytarabine BID on days -5 to -2, etoposide BID on days -5 to -2, and melphalan on day -1. Patients undergo infusion of lentivirus vector CCR5 shRNA/TRIM5alpha/TAR decoy-transduced autologous CD34-positive hematopoietic progenitor cells over 1 hour.

Autologous Hematopoietic Stem Cell Transplantation: Undergo infusion of lentivirus vector CCR5 shRNA/TRIM5alpha/TAR decoy-transduced autologous CD34-positive hematopoietic progenitor cells

Carmustine: 300 mg/m2 on Day -6, as part of BEAM and R-BEAM regimens.

Cytarabine: 100 mg/m2 BID on Days -5 through -2, as part of BEAM and R-BEAM regimens.

Etoposide: VP-16: 100 mg/m2 BID on Days -5 through -2, as part of BEAM and R-BEAM regimens.

Laboratory Biomarker Analysis: Correlative studies

Lentivirus Vector CCR5 shRNA/TRIM5alpha/TAR Decoy-transduced Autologous CD34-positive Hematopoietic Progenitor Cells: Undergo infusion of lentivirus vector CCR5 shRNA/TRIM5alpha/TAR decoy-transduced autologous CD34-positive hematopoietic progenitor cells

Melphalan: 140 mg/m2 on Day -1, as part of BEAM and R-BEAM regimens.

Peripheral Blood Stem Cell Transplantation: Undergo infusion of lentivirus vector CCR5 shRNA/TRIM5alpha/TAR decoy-transduced autologous CD34-positive hematopoietic progenitor cells

Treatment (Anti-HIV Gene Transduced CD34+ Cells): 1:0 Ratio

Patients receive BEAM regimen administered as standard of care comprising carmustine on day -6, cytarabine BID on days -5 to -2, etoposide BID on days -5 to -2, and melphalan on day -1. Patients undergo infusion of lentivirus vector CCR5 shRNA/TRIM5alpha/TAR decoy-transduced autologous CD34-positive hematopoietic progenitor cells over 1 hour.

Autologous Hematopoietic Stem Cell Transplantation: Undergo infusion of lentivirus vector CCR5 shRNA/TRIM5alpha/TAR decoy-transduced autologous CD34-positive hematopoietic progenitor cells

Treatment (Anti-HIV Gene Transduced CD34+ Cells): 1:1 Ratio

Treatment (Anti-HIV Gene Transduced CD34+ Cells): 5:1 Ratio

Treatment (Anti-HIV Gene Transduced CD34+ Cells)

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Bone Marrow Biopsy status

Participants received Stem Cell Gene Therapy

Deukwoo Kwon

Percentage of Participants Who Achieve a Timely Engraftment

Proportion of Study Participants Who Achieve Greater Than 5% Mononuclear Blood Cells Expressing Anti-HIV Genes in Peripheral Blood

Proportion of Study Participants With Gene Modified HIV-1 Resistant Peripheral Blood Cells and Gut Mucosal Immune Cells

Quantity of Gene Modified HIV-1 Resistant Peripheral Blood Cells and Gut Mucosal Immune Cells

Integration Sites of Vector Sequences in Circulating Cells

Progression-free Survival

Number of Participants With a Complete Response

Number of Days From the First Documentation of a Complete Response Until the First Day of Relapse

Partial Response Rate and Duration

Time to Neutrophil Engraftment

Time to Platelet Engraftment

Number of Participants With an Absolute Neutrophil Count of at Least 1500 Cells/mm3, Hemoglobin of at Least 10 g/dL, and Platelets Greater Than 100,000.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Memory-enriched CAR-T Cells Immunotherapy for B Cell Lymphoma	NCT02652910	Recurrent Adult... Recurrent Folli... Recurrent Mantl... Stage III Adult... Stage III Folli... Stage III Mantl... Stage IV Adult ... Stage IV Follic... Stage IV Mantle...	CD19.CAR-T cell...	18 Years - 70 Years	Xinqiao Hospital of Chongqing
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
Gene Therapy in Treating Patients With Human Immunodeficiency Virus-Related Lymphoma Receiving Stem Cell Transplant	NCT02797470	HIV Infection Mature T-Cell a... Plasmablastic L... Recurrent Adult... Recurrent Adult... Recurrent Burki... Recurrent Folli... Stage III Folli... Stage III Mantl... Stage IV Follic... Stage IV Mantle...	Autologous Hema... Carmustine Cytarabine Etoposide Laboratory Biom... Lentivirus Vect... Melphalan Peripheral Bloo...	18 Years -	AIDS Malignancy Consortium

Spots Global Cancer Trial Database for stage iii follicular lymphoma