Genetically Engineered Lymphocyte Therapy After Peripheral Blood Stem Cell Transplant in Treating Patients With High-Risk, Intermediate-Grade, B-cell Non-Hodgkin Lymphoma

• Sponsor: City of Hope Medical Center (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01318317
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 8
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 131.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This phase I/II trial studies the side effects and best dose of genetically engineered lymphocyte therapy and to see how well it works after peripheral blood stem cell transplant (PBSCT) in treating patients with high-risk, intermediate-grade, B-cell non-Hodgkin lymphoma (NHL). Genetically engineered lymphocyte therapy may stimulate the immune system in different ways and stop cancer cells from growing. Giving rituximab together with chemotherapy before a PBSCT stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as filgrastim (G-CSF), or plerixafor helps stem cells move from the bone marrow to the blood so they can be collected and stored. More chemotherapy or radiation therapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Giving genetically engineered lymphocyte therapy after PBSCT may be an effective treatment for NHL.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Non-Hodgkin Lymphoma	Procedure: Autologous Hematopoietic Stem Cell Transplantation; Biological: Filgrastim; Biological: Genetically Engineered Lymphocyte Therapy; Other: Laboratory Biomarker Analysis; Procedure: Peripheral Blood Stem Cell Transplantation; Drug: Plerixafor; Biological: Rituximab	Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To assess the safety of cellular immunotherapy utilizing ex vivo expanded autologous central memory T cell (TCM)-enriched cluster of differentiation (CD)8+ T cells genetically-modified to express a CD19-specific chimeric antigen receptor (CAR) in conjunction with a standard myeloablative autologous hematopoietic stem cell transplantation (aHSCT) for research participants with high-risk intermediate grade B-lineage non-Hodgkin lymphomas who have relapsed after primary therapy, or who did not achieve complete remission with primary therapy. (Phase I) II. To determine the maximum tolerated dose (MTD) on dose limiting toxicities (DLTs) and to describe the full toxicity profile. (Phase I) III. To determine the rate of research participants receiving TCM-enriched CD8+ T cells genetically-modified to express a CD19-specific CAR for which the transferred cells are detected in the circulation 28 days (+/- 3 days) by woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) quantitative (Q)-polymerase chain reaction (PCR). (Phase II)

SECONDARY OBJECTIVES:

1. To determine the tempo, magnitude, and duration of engraftment of the transferred T cell product as it relates to the number of cells infused. (Phase II) II. To study the impact of this therapeutic intervention on the development of CD19+ B-cell precursors in the bone marrow as a surrogate for the in vivo effector function of transferred CD19-specific T cells. (Phase II) III. To describe the progression-free and overall survival of treated research participants on this protocol. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of genetically engineered lymphocyte therapy followed by a phase II study.

Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with filgrastim and/or plerixafor. Some patients may also receive rituximab intravenously (IV) within 4 weeks of transplant. Patients receive standard myeloablative conditioning followed by autologous PBSCT. Patients then undergo infusion of ex vivo expanded autologous TCM-enriched CD8+ T cells expressing CD19-specific CAR on day 2 or 3 after transplant.

After completion of study treatment, patients are followed up periodically for at least 15 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Study of Cellular Immunotherapy Using Central Memory-Enriched CD8+ T Cells Lentivirally Transduced to Express A CD19-Specific Chimeric Immunoreceptor Following Peripheral Blood Stem Cell Transplantation for Patients With High-Risk Intermediate Grade B-Lineage Non-Hodgkin Lymphoma
• Actual Study Start Date: Sep 19, 2011
• Actual Primary Completion Date: Oct 3, 2013
• Anticipated Study Completion Date: Aug 23, 2022

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (cellular adoptive immunotherapy following PBSCT) Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with G-CSF and/or plerixafor. Some patients may also receive rituximab IV within 4 weeks of transplant. Patients receive standard myeloablative conditioning followed by autologous PBSCT. Patients then undergo infusion of ex vivo expanded autologous TCM-enriched CD8+ T cells expressing CD19-specific CAR on day 2 or 3 after transplant.

Procedure: Autologous Hematopoietic Stem Cell Transplantation; Undergo autologous PBSCT; Other Names: AHSCT Autologous Autologous Hematopoietic Cell Transplantation Autologous Stem Cell Transplant Autologous Stem Cell Transplantation Stem Cell Transplantation, Autologous ; Biological: Filgrastim; Given IV; Other Names: Filgrastim-aafi G-CSF Neupogen Nivestym r-metHuG-CSF Recombinant Methionyl Human Granulocyte Colony Stimulating Factor rG-CSF Tevagrastim ; Biological: Genetically Engineered Lymphocyte Therapy; Receive ex vivo expanded autologous TCM-enriched CD8+ T cells expressing CD19-specific CAR; Other: Laboratory Biomarker Analysis; Correlative studies; Procedure: Peripheral Blood Stem Cell Transplantation; Undergo autologous PBSCT; Other Names: PBPC transplantation PBSCT Peripheral Blood Progenitor Cell Transplantation PERIPHERAL BLOOD STEM CELL TRANSPLANT Peripheral Stem Cell Support Peripheral Stem Cell Transplant Peripheral Stem Cell Transplantation ; Drug: Plerixafor; Given IV; Other Names: AMD 3100 JM-3100 Mozobil SDZ SID 791 ; Biological: Rituximab; Given IV; Other Names: ABP 798 BI 695500 C2B8 Monoclonal Antibody Chimeric Anti-CD20 Antibody CT-P10 IDEC-102 IDEC-C2B8 IDEC-C2B8 Monoclonal Antibody MabThera Monoclonal Antibody IDEC-C2B8 PF-05280586 Rituxan Rituximab ABBS Rituximab Biosimilar ABP 798 Rituximab Biosimilar BI 695500 Rituximab Biosimilar CT-P10 Rituximab Biosimilar GB241 Rituximab Biosimilar IBI301 Rituximab Biosimilar JHL1101 Rituximab Biosimilar PF-05280586 Rituximab Biosimilar RTXM83 Rituximab Biosimilar SAIT101 Rituximab Biosimilar SIBP-02 rituximab biosimilar TQB2303 rituximab-abbs RTXM83 Truxima

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Dose Limiting Toxicities (DLTs) [Within 28 days of T-cell infusion]

   Number of DLTs per dose level are reported. A DLT is defined as: Any grade 3 or higher toxicity, with the exception of expected adverse events; and designated as definitely or probably related (level of attribution) to the infusion of the TCM cells; and occurring within 28 days of T-cell infusion; Any toxicity requiring the use of steroids to ablate side effects attributable to the infusion of the TCM cells, and occurring within 28 days of T-cell infusion; Any toxicity which is a lower grade, but that increases in grade to a grade 3 or higher as a direct result of the TCM, and occurring within 28 days of T-cell infusion; Any grade 2 or greater autoimmune toxicity, and occurring within 28 days of T-cell infusion.

2. Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) Detection Above Background [28 days post T cell infusion]

   Peak expansion of WPRE is expressed in CAR copy number/mL of blood is summarized with median and range

3. Number of Days of Quantifiable CD19 CAR Post T-cell Infusion [28 days post T cell infusion]

   WPRE persistence of quantifiable CD19 CAR summarized with mean and standard deviation

Secondary Outcome Measures

1. Failure to Engraft [Within 21 days post T-cell infusion]

   Count of participants who fail to engraft post transplant.

2. Progression-free Survival at 1 Year [Up to 1 year]

   Estimated using the Kaplan-Meier methods. Progression is defined using the revised IWG response criteria, as any new lesion or increase by ≥50% of previously involved sites from nadir.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• City of Hope (COH) pathology review confirms that research participant's diagnostic material is consistent with history of intermediate grade B-cell NHL (e.g., diffuse B-cell lymphoma, mantle cell lymphoma, transformed follicular lymphoma)

• History of relapse after achieving first remission with primary therapy, or failure to achieve remission with primary therapy

• Life expectancy > 16 weeks

• Karnofsky performance scale (KPS) >= 70%

• Negative serum pregnancy test for women of childbearing potential

• Research participant has an indication to be considered for autologous stem cell transplantation

Exclusion Criteria:

• Fails to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I/II study; evidence of understanding includes passing the Protocol Comprehensive Screening given by the Research Subject Advocate (RSA); a legal guardian may substitute for the research participant

• Any standard contraindications to myeloablative HSCT per standard of care practices at COH

• Dependence on corticosteroids

• Currently enrolled in another investigational therapy protocol

• Human immunodeficiency virus (HIV) seropositive based on testing performed within 4 weeks of enrollment

• History of allogeneic HSCT or prior autologous HSCT

• Active autoimmune disease requiring systemic immunosuppressive therapy

• Research participant(s) who are to receive radioimmunotherapy (Zevalin-based)-based conditioning regimens

• Research participant(s) with known active hepatitis B or C infection

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Medical Center	Duarte	California	United States	91010

Sponsors and Collaborators

• City of Hope Medical Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Leslie L Popplewell, City of Hope Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 10, 2014

More Information

Publications

None provided.

• Responsible Party: City of Hope Medical Center
• ClinicalTrials.gov Identifier: NCT01318317
• Other Study ID Numbers: 09174; NCI-2011-00344; 09174; P30CA033572; P50CA107399
• First Posted: Mar 18, 2011
• Last Update Posted: Jul 26, 2022
• Last Verified: Jun 1, 2022

• Additional relevant MeSH terms: Lymphoma; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Lymphoma, Mantle-Cell; Recurrence; Plerixafor; Rituximab; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Lenograstim

Study Results

Participant Flow

Pre-assignment Detail	Three additional participants underwent leukapheresis, however, two were ineligible for transplant and the third refused additional treatment and therefore were not assigned a dose level.

Arm/Group Title	Dose Level 0 (25 x 10^6 CAR+ T-cells)	Dose Level 1 (50 x 10^6 CAR+ T-cells)	Dose Level 2 (100 x 10^6 CAR+ T-cells)
Arm/Group Description	Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with Granulocyte-Colony Stimulating Factor (G-CSF) and/or plerixafor. All patients receive rituximab IV within 4 weeks of transplantation. Patients receive standard myeloablative conditioning followed by autologous Peripheral Blood Stem Cell Transplant (PBSCT). Patients then undergo infusion of ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR) on day 2 or 3 after transplantation.	Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with Granulocyte-Colony Stimulating Factor (G-CSF) and/or plerixafor. All patients receive rituximab IV within 4 weeks of transplantation. Patients receive standard myeloablative conditioning followed by autologous Peripheral Blood Stem Cell Transplant (PBSCT). Patients then undergo infusion of ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR) on day 2 or 3 after transplantation.	Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with Granulocyte-Colony Stimulating Factor (G-CSF) and/or plerixafor. All patients receive rituximab IV within 4 weeks of transplantation. Patients receive standard myeloablative conditioning followed by autologous Peripheral Blood Stem Cell Transplant (PBSCT). Patients then undergo infusion of ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR) on day 2 or 3 after transplantation.
Period Title: Overall Study
STARTED	1	4	3
COMPLETED	1	4	3
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Dose Level 0 (25 x 10^6 CAR+ T-cells)	Dose Level 1 (50 x 10^6 CAR+ T-cells)	Dose Level 2 (100 x 10^6 CAR+ T-cells)	Total
Arm/Group Description	Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with Granulocyte-Colony Stimulating Factor (G-CSF) and/or plerixafor. Some patients may also receive rituximab IV within 4 weeks of transplantation. Patients receive standard myeloablative conditioning followed by autologous Peripheral Blood Stem Cell Transplant (PBSCT). Patients then undergo infusion of ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR) on day 2 or 3 after transplantation.	Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with Granulocyte-Colony Stimulating Factor (G-CSF) and/or plerixafor. Some patients may also receive rituximab IV within 4 weeks of transplantation. Patients receive standard myeloablative conditioning followed by autologous Peripheral Blood Stem Cell Transplant (PBSCT). Patients then undergo infusion of ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR) on day 2 or 3 after transplantation.	Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with Granulocyte-Colony Stimulating Factor (G-CSF) and/or plerixafor. Some patients may also receive rituximab IV within 4 weeks of transplantation. Patients receive standard myeloablative conditioning followed by autologous Peripheral Blood Stem Cell Transplant (PBSCT). Patients then undergo infusion of ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR) on day 2 or 3 after transplantation.	Total of all reporting groups
Overall Participants	1	4	3	8
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	75	60	58	62
Sex: Female, Male (Count of Participants)
Female	0 0%	3 75%	1 33.3%	4 50%
Male	1 100%	1 25%	2 66.7%	4 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	1 100%	4 100%	3 100%	8 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	1 100%	4 100%	3 100%	8 100%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	1 100%	4 100%	3 100%	8 100%
Disease histology (Count of Participants)
Diffuse Large B-Cell Lymphoma	1 100%	3 75%	3 100%	7 87.5%
Mantle Cell Lymphoma	0 0%	1 25%	0 0%	1 12.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Dose Limiting Toxicities (DLTs)
Description	Number of DLTs per dose level are reported. A DLT is defined as: Any grade 3 or higher toxicity, with the exception of expected adverse events; and designated as definitely or probably related (level of attribution) to the infusion of the TCM cells; and occurring within 28 days of T-cell infusion; Any toxicity requiring the use of steroids to ablate side effects attributable to the infusion of the TCM cells, and occurring within 28 days of T-cell infusion; Any toxicity which is a lower grade, but that increases in grade to a grade 3 or higher as a direct result of the TCM, and occurring within 28 days of T-cell infusion; Any grade 2 or greater autoimmune toxicity, and occurring within 28 days of T-cell infusion.
Time Frame	Within 28 days of T-cell infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Level 0 (25 x 10^6 CAR+ T-cells)	Dose Level 1 (50 x 10^6 CAR+ T-cells)	Dose Level 2 (100 x 10^6 CAR+ T-cells)
Arm/Group Description	Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with Granulocyte-Colony Stimulating Factor (G-CSF) and/or plerixafor. Some patients may also receive rituximab IV within 4 weeks of transplantation. Patients receive standard myeloablative conditioning followed by autologous Peripheral Blood Stem Cell Transplant (PBSCT). Patients then undergo infusion of ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR) on day 2 or 3 after transplantation.	Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with Granulocyte-Colony Stimulating Factor (G-CSF) and/or plerixafor. Some patients may also receive rituximab IV within 4 weeks of transplantation. Patients receive standard myeloablative conditioning followed by autologous Peripheral Blood Stem Cell Transplant (PBSCT). Patients then undergo infusion of ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR) on day 2 or 3 after transplantation.	Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with Granulocyte-Colony Stimulating Factor (G-CSF) and/or plerixafor. Some patients may also receive rituximab IV within 4 weeks of transplantation. Patients receive standard myeloablative conditioning followed by autologous Peripheral Blood Stem Cell Transplant (PBSCT). Patients then undergo infusion of ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR) on day 2 or 3 after transplantation.
Measure Participants	1	4	3
Count of Participants [Participants]	0 0%	0 0%	0 0%

2. Primary Outcome

Title	Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) Detection Above Background
Description	Peak expansion of WPRE is expressed in CAR copy number/mL of blood is summarized with median and range
Time Frame	28 days post T cell infusion

Outcome Measure Data

Analysis Population Description

1 participant in dose level 1 did not have any whole blood samples to analyze. Overall median was reported due to small samples sizes in each dose level.

Arm/Group Title	Treatment (Cellular Adoptive Immunotherapy Following PBSCT)
Arm/Group Description	Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with Granulocyte-Colony Stimulating Factor (G-CSF) and/or plerixafor. Some patients may also receive rituximab IV within 4 weeks of transplantation. Patients receive standard myeloablative conditioning followed by autologous Peripheral Blood Stem Cell Transplant (PBSCT). Patients then undergo infusion of ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR) on day 2 or 3 after transplantation. peripheral blood stem cell transplantation (PBSCT): Undergo autologous PBSCT filgrastim: Given IV polymerase chain reaction: Correlative studies rituximab: Given IV genetically engineered lymphocyte therapy: Receive ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR) laboratory biomarker analysis: Correlative studies plerixafor: Given IV autologous hematopoietic stem cell transplantation: Undergo autologous PBSCT
Measure Participants	7
Median (Full Range) [CAR copy number/mL]	280

3. Primary Outcome

Title	Number of Days of Quantifiable CD19 CAR Post T-cell Infusion
Description	WPRE persistence of quantifiable CD19 CAR summarized with mean and standard deviation
Time Frame	28 days post T cell infusion

Outcome Measure Data

Analysis Population Description

1 participant in dose level 1 did not have any whole blood samples to analyze. Overall mean was reported due to small samples sizes in each dose level.

Arm/Group Title	Treatment (Cellular Adoptive Immunotherapy Following PBSCT)
Arm/Group Description	Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with Granulocyte-Colony Stimulating Factor (G-CSF) and/or plerixafor. Some patients may also receive rituximab IV within 4 weeks of transplantation. Patients receive standard myeloablative conditioning followed by autologous Peripheral Blood Stem Cell Transplant (PBSCT). Patients then undergo infusion of ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR) on day 2 or 3 after transplantation. peripheral blood stem cell transplantation (PBSCT): Undergo autologous PBSCT filgrastim: Given IV polymerase chain reaction: Correlative studies rituximab: Given IV genetically engineered lymphocyte therapy: Receive ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR) laboratory biomarker analysis: Correlative studies plerixafor: Given IV autologous hematopoietic stem cell transplantation: Undergo autologous PBSCT
Measure Participants	7
Mean (Standard Deviation) [days]	18.25 (12.1)

4. Secondary Outcome

Title	Failure to Engraft
Description	Count of participants who fail to engraft post transplant.
Time Frame	Within 21 days post T-cell infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Level 0 (25 x 10^6 CAR+ T-cells)	Dose Level 1 (50 x 10^6 CAR+ T-cells)	Dose Level 2 (100 x 10^6 CAR+ T-cells)
Arm/Group Description	Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with Granulocyte-Colony Stimulating Factor (G-CSF) and/or plerixafor. Some patients may also receive rituximab IV within 4 weeks of transplantation. Patients receive standard myeloablative conditioning followed by autologous Peripheral Blood Stem Cell Transplant (PBSCT). Patients then undergo infusion of ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR) on day 2 or 3 after transplantation.	Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with Granulocyte-Colony Stimulating Factor (G-CSF) and/or plerixafor. Some patients may also receive rituximab IV within 4 weeks of transplantation. Patients receive standard myeloablative conditioning followed by autologous Peripheral Blood Stem Cell Transplant (PBSCT). Patients then undergo infusion of ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR) on day 2 or 3 after transplantation.	Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with Granulocyte-Colony Stimulating Factor (G-CSF) and/or plerixafor. Some patients may also receive rituximab IV within 4 weeks of transplantation. Patients receive standard myeloablative conditioning followed by autologous Peripheral Blood Stem Cell Transplant (PBSCT). Patients then undergo infusion of ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR) on day 2 or 3 after transplantation.
Measure Participants	1	4	3
Count of Participants [Participants]	0 0%	0 0%	0 0%

5. Secondary Outcome

Title	Progression-free Survival at 1 Year
Description	Estimated using the Kaplan-Meier methods. Progression is defined using the revised IWG response criteria, as any new lesion or increase by ≥50% of previously involved sites from nadir.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Cellular Adoptive Immunotherapy Following PBSCT)
Arm/Group Description	Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with Granulocyte-Colony Stimulating Factor (G-CSF) and/or plerixafor. Some patients may also receive rituximab IV within 4 weeks of transplantation. Patients receive standard myeloablative conditioning followed by autologous Peripheral Blood Stem Cell Transplant (PBSCT). Patients then undergo infusion of ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR) on day 2 or 3 after transplantation. peripheral blood stem cell transplantation (PBSCT): Undergo autologous PBSCT filgrastim: Given IV polymerase chain reaction: Correlative studies rituximab: Given IV genetically engineered lymphocyte therapy: Receive ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR) laboratory biomarker analysis: Correlative studies plerixafor: Given IV autologous hematopoietic stem cell transplantation: Undergo autologous PBSCT
Measure Participants	8
Number (95% Confidence Interval) [percentage of participants]	50 5000%

Adverse Events

Time Frame	During and after treatment, up to 38 months
Arm/Group Title	Dose Level 0 (25 x 10^6 CAR+ T-cells)		Dose Level 1 (50 x 10^6 CAR+ T-cells)		Dose Level 2 (100 x 10^6 CAR+ T-cells)
Arm/Group Description	Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with Granulocyte-Colony Stimulating Factor (G-CSF) and/or plerixafor. Some patients may also receive rituximab IV within 4 weeks of transplantation. Patients receive standard myeloablative conditioning followed by autologous Peripheral Blood Stem Cell Transplant (PBSCT). Patients then undergo infusion of ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR) on day 2 or 3 after transplantation.		Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with Granulocyte-Colony Stimulating Factor (G-CSF) and/or plerixafor. Some patients may also receive rituximab IV within 4 weeks of transplantation. Patients receive standard myeloablative conditioning followed by autologous Peripheral Blood Stem Cell Transplant (PBSCT). Patients then undergo infusion of ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR) on day 2 or 3 after transplantation.		Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with Granulocyte-Colony Stimulating Factor (G-CSF) and/or plerixafor. Some patients may also receive rituximab IV within 4 weeks of transplantation. Patients receive standard myeloablative conditioning followed by autologous Peripheral Blood Stem Cell Transplant (PBSCT). Patients then undergo infusion of ex vivo expanded autologous central memory (TCM)-enriched CD8+ T cells expressing CD19-specific chimeric antigen receptor (CAR) on day 2 or 3 after transplantation.
All Cause Mortality
	Dose Level 0 (25 x 10^6 CAR+ T-cells)		Dose Level 1 (50 x 10^6 CAR+ T-cells)		Dose Level 2 (100 x 10^6 CAR+ T-cells)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		1/4 (25%)		1/3 (33.3%)
Serious Adverse Events
	Dose Level 0 (25 x 10^6 CAR+ T-cells)		Dose Level 1 (50 x 10^6 CAR+ T-cells)		Dose Level 2 (100 x 10^6 CAR+ T-cells)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		2/4 (50%)		3/3 (100%)
Cardiac disorders
Atrial fibrillation	0/1 (0%)		1/4 (25%)		0/3 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant, and unspecified (incl cysts and polyps)- Other	0/1 (0%)		0/4 (0%)		1/3 (33.3%)
Nervous system disorders
Stroke	0/1 (0%)		0/4 (0%)		1/3 (33.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/1 (0%)		0/4 (0%)		1/3 (33.3%)
Pulmonary edema	0/1 (0%)		1/4 (25%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Dose Level 0 (25 x 10^6 CAR+ T-cells)		Dose Level 1 (50 x 10^6 CAR+ T-cells)		Dose Level 2 (100 x 10^6 CAR+ T-cells)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		4/4 (100%)		3/3 (100%)
Blood and lymphatic system disorders
Anemia	1/1 (100%)		4/4 (100%)		3/3 (100%)
Febrile neutropenia	1/1 (100%)		2/4 (50%)		3/3 (100%)
Cardiac disorders
Pericardial effusion	0/1 (0%)		0/4 (0%)		1/3 (33.3%)
Sinus bradycardia	0/1 (0%)		1/4 (25%)		1/3 (33.3%)
Sinus tachycardia	1/1 (100%)		4/4 (100%)		2/3 (66.7%)
Gastrointestinal disorders
Abdominal distension	1/1 (100%)		1/4 (25%)		0/3 (0%)
Abdominal pain	1/1 (100%)		2/4 (50%)		2/3 (66.7%)
Constipation	1/1 (100%)		2/4 (50%)		2/3 (66.7%)
Dental caries	0/1 (0%)		1/4 (25%)		0/3 (0%)
Diarrhea	1/1 (100%)		4/4 (100%)		3/3 (100%)
Dry mouth	0/1 (0%)		1/4 (25%)		2/3 (66.7%)
Fecal incontinence	0/1 (0%)		0/4 (0%)		1/3 (33.3%)
Flatulence	1/1 (100%)		2/4 (50%)		0/3 (0%)
Mucositis oral	1/1 (100%)		3/4 (75%)		2/3 (66.7%)
Nausea	1/1 (100%)		4/4 (100%)		3/3 (100%)
Oral pain	0/1 (0%)		0/4 (0%)		1/3 (33.3%)
Rectal hemorrhage	0/1 (0%)		0/4 (0%)		1/3 (33.3%)
Rectal pain	0/1 (0%)		1/4 (25%)		0/3 (0%)
Rectal ulcer	0/1 (0%)		0/4 (0%)		1/3 (33.3%)
Typhlitis	0/1 (0%)		1/4 (25%)		0/3 (0%)
Vomiting	1/1 (100%)		3/4 (75%)		3/3 (100%)
General disorders
Chills	1/1 (100%)		1/4 (25%)		1/3 (33.3%)
Fatigue	1/1 (100%)		4/4 (100%)		3/3 (100%)
Fever	1/1 (100%)		3/4 (75%)		3/3 (100%)
Injection site reaction	0/1 (0%)		1/4 (25%)		0/3 (0%)
Pain	0/1 (0%)		2/4 (50%)		1/3 (33.3%)
Edema limbs	1/1 (100%)		2/4 (50%)		2/3 (66.7%)
Infusion related reaction	0/1 (0%)		1/4 (25%)		1/3 (33.3%)
Localized edema	0/1 (0%)		1/4 (25%)		0/3 (0%)
Non-cardiac chest pain	0/1 (0%)		1/4 (25%)		0/3 (0%)
Infections and infestations
Catheter related infection	0/1 (0%)		0/4 (0%)		1/3 (33.3%)
Eye infection	0/1 (0%)		1/4 (25%)		0/3 (0%)
Infections and infestations - Other, specify	0/1 (0%)		1/4 (25%)		0/3 (0%)
Upper respiratory infection	0/1 (0%)		1/4 (25%)		1/3 (33.3%)
Soft tissue infection	1/1 (100%)		0/4 (0%)		0/3 (0%)
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications - Other, specify	0/1 (0%)		0/4 (0%)		1/3 (33.3%)
Vascular access complication	0/1 (0%)		1/4 (25%)		0/3 (0%)
Investigations
Alanine aminotransferase increased	0/1 (0%)		2/4 (50%)		2/3 (66.7%)
Alkaline phosphatase increased	0/1 (0%)		0/4 (0%)		1/3 (33.3%)
Aspartate aminotransferase increased	1/1 (100%)		3/4 (75%)		3/3 (100%)
Blood bilirubin increased	0/1 (0%)		0/4 (0%)		1/3 (33.3%)
Cholesterol high	0/1 (0%)		1/4 (25%)		0/3 (0%)
Creatinine increased	0/1 (0%)		3/4 (75%)		3/3 (100%)
Lymphocyte count decreased	1/1 (100%)		4/4 (100%)		3/3 (100%)
Lymphocyte count increased	0/1 (0%)		2/4 (50%)		0/3 (0%)
Neutrophil count decreased	1/1 (100%)		4/4 (100%)		3/3 (100%)
Platelet count decreased	1/1 (100%)		4/4 (100%)		3/3 (100%)
Weight loss	0/1 (0%)		2/4 (50%)		3/3 (100%)
White blood cell decreased	1/1 (100%)		4/4 (100%)		3/3 (100%)
Metabolism and nutrition disorders
Anorexia	1/1 (100%)		4/4 (100%)		3/3 (100%)
Dehydration	0/1 (0%)		2/4 (50%)		1/3 (33.3%)
Hypercalcemia	0/1 (0%)		0/4 (0%)		1/3 (33.3%)
Hyperglycemia	0/1 (0%)		2/4 (50%)		0/3 (0%)
Hyperkalemia	0/1 (0%)		0/4 (0%)		1/3 (33.3%)
Hypermagnesemia	0/1 (0%)		1/4 (25%)		0/3 (0%)
Hypernatremia	0/1 (0%)		0/4 (0%)		1/3 (33.3%)
Hypertriglyceridemia	0/1 (0%)		1/4 (25%)		1/3 (33.3%)
Hypoalbuminemia	1/1 (100%)		4/4 (100%)		3/3 (100%)
Hypocalcemia	1/1 (100%)		4/4 (100%)		0/3 (0%)
Hypoglycemia	1/1 (100%)		3/4 (75%)		2/3 (66.7%)
Hypokalemia	1/1 (100%)		3/4 (75%)		2/3 (66.7%)
Hypomagnesemia	0/1 (0%)		1/4 (25%)		1/3 (33.3%)
Hyponatremia	1/1 (100%)		4/4 (100%)		3/3 (100%)
Hypophosphatemia	0/1 (0%)		2/4 (50%)		1/3 (33.3%)
Musculoskeletal and connective tissue disorders
Back pain	0/1 (0%)		1/4 (25%)		2/3 (66.7%)
Bone pain	0/1 (0%)		2/4 (50%)		0/3 (0%)
Myalgia	0/1 (0%)		1/4 (25%)		0/3 (0%)
Neck pain	0/1 (0%)		0/4 (0%)		1/3 (33.3%)
Pain in extremity	1/1 (100%)		2/4 (50%)		1/3 (33.3%)
Generalized muscle weakness	1/1 (100%)		1/4 (25%)		0/3 (0%)
Nervous system disorders
Dizziness	1/1 (100%)		1/4 (25%)		1/3 (33.3%)
Dysgeusia	1/1 (100%)		0/4 (0%)		0/3 (0%)
Headache	1/1 (100%)		3/4 (75%)		3/3 (100%)
Paresthesia	0/1 (0%)		0/4 (0%)		2/3 (66.7%)
Peripheral sensory neuropathy	0/1 (0%)		1/4 (25%)		1/3 (33.3%)
Presyncope	0/1 (0%)		1/4 (25%)		0/3 (0%)
Psychiatric disorders
Anxiety	0/1 (0%)		3/4 (75%)		2/3 (66.7%)
Confusion	0/1 (0%)		2/4 (50%)		0/3 (0%)
Insomnia	1/1 (100%)		2/4 (50%)		2/3 (66.7%)
Restlessness	1/1 (100%)		2/4 (50%)		1/3 (33.3%)
Renal and urinary disorders
Hematuria	0/1 (0%)		2/4 (50%)		1/3 (33.3%)
Proteinuria	0/1 (0%)		2/4 (50%)		0/3 (0%)
Renal colic	0/1 (0%)		0/4 (0%)		1/3 (33.3%)
Urinary frequency	0/1 (0%)		1/4 (25%)		0/3 (0%)
Urinary incontinence	0/1 (0%)		1/4 (25%)		0/3 (0%)
Bladder spasm	0/1 (0%)		1/4 (25%)		0/3 (0%)
Urinary tract obstruction	0/1 (0%)		0/4 (0%)		1/3 (33.3%)
Urinary tract pain	0/1 (0%)		1/4 (25%)		1/3 (33.3%)
Reproductive system and breast disorders
Breast pain	0/1 (0%)		2/4 (50%)		0/3 (0%)
Testicular pain	0/1 (0%)		0/4 (0%)		1/3 (33.3%)
Vaginal pain	0/1 (0%)		1/4 (25%)		0/3 (0%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	0/1 (0%)		1/4 (25%)		0/3 (0%)
Atelectasis	0/1 (0%)		1/4 (25%)		0/3 (0%)
Cough	1/1 (100%)		2/4 (50%)		3/3 (100%)
Dyspnea	0/1 (0%)		2/4 (50%)		1/3 (33.3%)
Epistaxis	1/1 (100%)		0/4 (0%)		0/3 (0%)
Hypoxia	0/1 (0%)		1/4 (25%)		0/3 (0%)
Nasal congestion	0/1 (0%)		0/4 (0%)		3/3 (100%)
Pharyngolaryngeal pain	0/1 (0%)		1/4 (25%)		0/3 (0%)
Pleural effusion	0/1 (0%)		2/4 (50%)		1/3 (33.3%)
Pneumonitis	0/1 (0%)		1/4 (25%)		0/3 (0%)
Sore throat	0/1 (0%)		1/4 (25%)		1/3 (33.3%)
Voice alteration	0/1 (0%)		1/4 (25%)		0/3 (0%)
Wheezing	0/1 (0%)		0/4 (0%)		1/3 (33.3%)
Pharyngeal mucositis	0/1 (0%)		1/4 (25%)		0/3 (0%)
Skin and subcutaneous tissue disorders
Alopecia	0/1 (0%)		3/4 (75%)		0/3 (0%)
Dry skin	1/1 (100%)		0/4 (0%)		0/3 (0%)
Erythema multiforme	0/1 (0%)		0/4 (0%)		1/3 (33.3%)
Pruritus	0/1 (0%)		0/4 (0%)		1/3 (33.3%)
Rash maculo-papular	1/1 (100%)		3/4 (75%)		2/3 (66.7%)
Skin and subcutaneous tissue disorders - Other, specify	0/1 (0%)		0/4 (0%)		1/3 (33.3%)
Skin hyperpigmentation	0/1 (0%)		1/4 (25%)		0/3 (0%)
Scalp pain	0/1 (0%)		0/4 (0%)		1/3 (33.3%)
Surgical and medical procedures
Surgical and medical procedures - Other, specify	0/1 (0%)		0/4 (0%)		1/3 (33.3%)
Vascular disorders
Hypertension	1/1 (100%)		4/4 (100%)		3/3 (100%)
Lymphedema	0/1 (0%)		1/4 (25%)		0/3 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.