NCT01318317

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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
8

participants targeted

Target at below P25 for phase_1

Timeline
10mo left

Started Sep 2011

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress95%
Sep 2011Feb 2027

First Submitted

Initial submission to the registry

March 16, 2011

Completed
2 days until next milestone

First Posted

Study publicly available on registry

March 18, 2011

Completed
6 months until next milestone

Study Start

First participant enrolled

September 19, 2011

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 3, 2013

Completed
8.2 years until next milestone

Results Posted

Study results publicly available

December 21, 2021

Completed
5.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 24, 2027

Expected
Last Updated

May 5, 2026

Status Verified

April 1, 2026

Enrollment Period

2 years

First QC Date

March 16, 2011

Results QC Date

September 21, 2021

Last Update Submit

April 22, 2026

Conditions

Recurrent Grade 1 Follicular LymphomaRecurrent Grade 2 Follicular LymphomaRecurrent Grade 3 Follicular LymphomaRecurrent Mantle Cell LymphomaRecurrent Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (3)

  • Number of Participants With Dose Limiting Toxicities (DLTs)

    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.

    Within 28 days of T-cell infusion

  • Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) Detection Above Background

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

    28 days post T cell infusion

  • Number of Days of Quantifiable CD19 CAR Post T-cell Infusion

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

    28 days post T cell infusion

Secondary Outcomes (2)

  • Failure to Engraft

    Within 21 days post T-cell infusion

  • Progression-free Survival at 1 Year

    Up to 1 year

Study Arms (1)

Treatment (cellular adoptive immunotherapy following PBSCT)

EXPERIMENTAL

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 TransplantationBiological: FilgrastimBiological: Genetically Engineered Lymphocyte TherapyOther: Laboratory Biomarker AnalysisProcedure: Peripheral Blood Stem Cell TransplantationDrug: PlerixaforBiological: Rituximab

Interventions

Genetically Engineered Lymphocyte TherapyBIOLOGICAL

Receive ex vivo expanded autologous TCM-enriched CD8+ T cells expressing CD19-specific CAR

Treatment (cellular adoptive immunotherapy following PBSCT)
Peripheral Blood Stem Cell TransplantationPROCEDURE

Undergo autologous PBSCT

Also known as: 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
Treatment (cellular adoptive immunotherapy following PBSCT)
Laboratory Biomarker AnalysisOTHER

Correlative studies

Treatment (cellular adoptive immunotherapy following PBSCT)
PlerixaforDRUG

Given IV

Also known as: AMD 3100, JM-3100, Mozobil, SDZ SID 791
Treatment (cellular adoptive immunotherapy following PBSCT)
RituximabBIOLOGICAL

Given IV

Also known as: 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
Treatment (cellular adoptive immunotherapy following PBSCT)
Autologous Hematopoietic Stem Cell TransplantationPROCEDURE

Undergo autologous PBSCT

Also known as: AHSCT, Autologous, Autologous Hematopoietic Cell Transplantation, Autologous Stem Cell Transplant, Autologous Stem Cell Transplantation, Stem Cell Transplantation, Autologous
Treatment (cellular adoptive immunotherapy following PBSCT)
FilgrastimBIOLOGICAL

Given IV

Also known as: Filgrastim-aafi, G-CSF, Neupogen, Nivestym, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tevagrastim
Treatment (cellular adoptive immunotherapy following PBSCT)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Related Publications (2)

  • Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

    PMID: 34515338DERIVED

  • Wang X, Popplewell LL, Wagner JR, Naranjo A, Blanchard MS, Mott MR, Norris AP, Wong CW, Urak RZ, Chang WC, Khaled SK, Siddiqi T, Budde LE, Xu J, Chang B, Gidwaney N, Thomas SH, Cooper LJ, Riddell SR, Brown CE, Jensen MC, Forman SJ. Phase 1 studies of central memory-derived CD19 CAR T-cell therapy following autologous HSCT in patients with B-cell NHL. Blood. 2016 Jun 16;127(24):2980-90. doi: 10.1182/blood-2015-12-686725. Epub 2016 Apr 26.

    PMID: 27118452DERIVED

MeSH Terms

Conditions

Lymphoma, FollicularLymphoma, Mantle-CellLymphoma, Non-Hodgkin

Interventions

Stem Cell TransplantationFilgrastimGranulocyte Colony-Stimulating FactorPeripheral Blood Stem Cell Transplantationplerixaforferric pyrophosphateRituximabCT-P10

Condition Hierarchy (Ancestors)

LymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Cell TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsTransplantationSurgical Procedures, OperativeColony-Stimulating FactorsGlycoproteinsGlycoconjugatesCarbohydratesHematopoietic Cell Growth FactorsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsProteinsBiological FactorsHematopoietic Stem Cell TransplantationAntibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsSerum GlobulinsGlobulins

Results Point of Contact

Title
Dr. Lwaliw Popplewell
Organization
City of Hope
lpopplewell@coh.org
626-359-8111

Study Officials

  • Elizabeth L Budde, MD,PhD

    City of Hope Medical Center

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 16, 2011

First Posted

March 18, 2011

Study Start

September 19, 2011

Primary Completion

October 3, 2013

Study Completion (Estimated)

February 24, 2027

Last Updated

May 5, 2026

Results First Posted

December 21, 2021

Record last verified: 2026-04

Locations

US(1)