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Lymphoma, Non-HodgkinPhase 1NCT03019055

Study of CAR-20/19-T Cells in Patients With Relapsed Refractory B Cell

A Phase 1 study testing CAR-20/19-T cells (1.0 x10^5 CAR-20/19-T cells/kg), CAR-20/19-T cells (2.5 x10^5 CAR-20/19-T cells/kg) and CAR-20/19-T cells (7.5 x10^5 CAR-20/19-T cells/kg) in people with Lymphoma, Non-Hodgkin and Lymphoma, B-Cell, run by Medical College of Wisconsin at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a phase 1/1b, interventional single arm, open label, treatment study designed to evaluate the safety and feasibility of infusion of autologous T cells engineered to contain an anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) single chain variable fragment (scFv) coupled… Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
CAR-20/19-T cells (1.0 x10^5 CAR-20/19-T cells/kg), CAR-20/19-T cells (2.5 x10^5 CAR-20/19-T cells/kg) and CAR-20/19-T cells (7.5 x10^5 CAR-20/19-T cells/kg)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
1 siteUnited States
Study dates
16 Oct 2017to 24 Aug 2021
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of B-cell non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL) / small lymphocytic leukemia (SLL): Patients must be aged≥18 years with relapsed, refractory disease and no available curative options that meet clinical criteria to initiate treatment.
  • Patients with B-cell NHL or CLL/SLL must have either CD19 or CD20 positive disease on most recent biopsy performed (a repeat biopsy is not mandatory for this study except as noted below). A minimum of 5% CD19 or CD20 positivity by immunohistochemistry or flow cytometry on prior or repeat biopsy is required.
  • Absolute CD3+ T cell count ≥50/mm^3.
  • MRI brain and Lumbar Puncture with cerebral spinal fluid (CSF) analysis by cytology and flow cytometry without evidence of central nervous system (CNS) involvement only in patients with history of CNS involvement.
  • Measurable disease must have been documented within 4 weeks of the time of consent defined as the following by disease specific subtype:
  • B-cell NHL: Active disease defined as nodal lesions greater than 20 mm in the long axis or extranodal lesions >10 mm in long and short axis or bone marrow involvement that is biopsy proven.
Show all 25Show fewer
  • CLL/SLL: Active disease by either bone marrow, peripheral flow cytometry, or CT and/or positron emission tomography (PET) imaging with nodal disease.
  • Patients should have failed at least two lines of a standard treatment and meet disease specific criteria detailed below:
  • CLL/SLL: measurable disease as defined above that has relapsed after at least one line of chemo-immunotherapy and progressed or intolerant to ibrutinib monotherapy.
  • CD19 or CD20 positive B cell NHL limited to the following histologies: Advanced Stage III or IV Follicular Lymphoma, Diffuse Large B cell Lymphoma and associated subtypes (e.g. aggressive B-cell lymphoma, T-cell/histocyte rich B-cell lymphoma, primary mediastinal B-cell lymphoma, Epstein Barr virus positive diffuse large B-cell lymphoma, transformed lymphoma such as transformed follicular or marginal zone lymphoma, and Richter's transformation) and Mantle cell lymphoma. Specific criteria include:
  • Patients must have active, measurable disease after two lines of cytotoxic chemotherapy of which one must be anthracycline containing.
  • Must have received Rituximab or another CD20 antibody and at minimum two chemotherapy regimens appropriate for their disease.
  • Either failed autologous transplant or ineligible to receive autologous transplant
  • Karnofsky performance score ≥70. See Appendix A for scales.
  • Normal Baseline Neurological Evaluation: Mini-Mental Status Exam Score 24-30.
  • Adequate hepatic function, defined as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <5 x upper limit of normal (ULN); serum bilirubin and alkaline phosphatase <5 x ULN, or considered not clinically significant as per the clinical PIs discretion (e.g. Gilbert's or indirect hyperbilirubinemia) or felt to be due to underlying disease.
  • Adequate renal function, defined as creatinine clearance>60 ml/min
  • Able to provide written informed consent.
  • Agree to practice birth control during the study.
  • Adequate cardiac function as indicated by New York Heart Association (NYHA) classification I or II AND left ventricular ejection fraction of ≥35% (by echocardiogram or MUGA) and adequate pulmonary function as indicated by room air oxygen saturation of ≥92%.
  • Expected survival >12 weeks.
  • Negative urine or serum pregnancy test in females of child bearing potential at study entry and again within 48 hours' prior lymphodepleting chemotherapy.
  • Patients with prior blinatumomab treatment require repeat biopsy post-blinatumomab treatment that demonstrates CD19 or CD20 positive disease.
  • Meet criteria for regarding fertility and contraception.
  • Central line access will be required for CAR-20/19-T cell infusion.

Who cannot join

  • Positive beta-human chorionic gonadotropin in females of child-bearing potential.
  • Patients with known systemic allergy to bovine or murine products.
  • Known prior positive serology for human anti-mouse antibody (HAMA).
  • Confirmed active human immunodeficiency virus (HIV), Hepatitis B or C infection.
  • History of significant autoimmune disease OR active, uncontrolled autoimmune phenomenon: such as systemic lupus erythematous, Wegner's glomerulonephritis, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura (AIHA, ITP) requiring steroid therapy defined as >20 mg of prednisone or equivalent daily.
  • Presence of ≥grade 3 non-hematologic toxicities as per CTCAE version 5.0 from any previous treatment unless it is felt to be due to underlying disease.
Show all 27Show fewer
  • Concurrent use of investigational therapeutic agents or enrollment on another therapeutic clinical trial at any institution. Minimum of ≥4 weeks required from administration of any other investigational agents on other clinical trials prior to enrollment on this CAR-T protocol.
  • Refusal to participate in the long-term follow-up protocol.
  • Patients with active CNS involvement by malignancy on MRI or by lumbar puncture.
  • Patients with prior CNS disease that has been effectively treated will be eligible providing treatment was >4 weeks before enrollment and a remission documented within 8 weeks of planned CAR-T cell infusion by MRI brain and CSF analysis.
  • Previous recipients of allogeneic hematopoietic stem cell transplantation (AHCT) are excluded if they are <100 days' post-transplant, have evidence of active graft-versus-host-disease (GVHD) of any grade, or are currently on immunosuppression.
  • Previous CAR-T cell therapy directed at either CD19 or CD20 within 100 days of planned CAR-20/19-T cell infusion (does not include re-enrollment)
  • Patients with prior CAR-T treatment against CD19 or CD20 must have repeat biopsy confirming a minimum of 5% CD19 or CD20 positivity by immunohistochemistry or flow cytometry.
  • Anti-CD20 antibody treatment within 4 weeks of cell infusion.
  • Anti-CD19 antibody treatment within 4 weeks of cell infusion.
  • Cytotoxic chemotherapy other than lymphodepletion within 14 days of CAR-T cell infusion.
  • Cytotoxic chemotherapy treatment within 14 days or steroid treatment (other than replacement dose steroids) within 7 days prior to apheresis collection for CAR-T cells.
  • Patients post solid organ transplant who develop high grade lymphomas or leukemias.
  • Concurrent active malignancy other than basal or squamous cell carcinomas of the skin.
  • Special Criteria for regarding Fertility and Contraception
  • Female subjects of reproductive potential (women who have reached menarche or women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, or have not undergone a sterilization procedure [hysterectomy or bilateral oophorectomy]) must have a negative serum or urine pregnancy test performed as part of eligibility criteria and again within 48 hours of initiation of lymphodepleting chemotherapy.
  • Due to the high-risk level of this study, while enrolled, all subjects must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization). Additionally, if participating in sexual activity that could lead to pregnancy, the study subject must agree to use reliable and double barrier methods of contraception during the follow-up period of the protocol.
  • Acceptable birth control includes a combination of two of the following methods:
  • Condoms* (male or female) with or without a spermicidal agent.
  • Diaphragm or cervical cap with spermicide
  • Intrauterine device (IUD)
  • Hormonal-based contraception Subjects who are not of reproductive potential (women who are premenarche or have been post-menopausal for at least 24 consecutive months or have undergone hysterectomy tubal ligation, salpingectomy, and/or bilateral oophorectomy or men who have documented azoospermia) are eligible without requiring the use of contraception.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Froedtert Hospital & Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

Other trials in United States

About this study

Official title: Phase 1/1b Study of Redirected Autologous T Cells Engineered to Contain an Anti CD19 and Anti CD20 scFv Coupled to CD3ζ and 4-1BB Signaling Domains in Patients With Relapsed and/or Refractory CD19 or CD20 Positive B Cell Malignancies

This is a phase 1/1b, interventional single arm, open label, treatment study designed to evaluate the safety and feasibility of infusion of autologous T cells engineered to contain an anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) single chain variable fragment (scFv) coupled to cluster of differentiation CD3ζ (CD3ζ) and co-stimulatory domain 4-1BB (4-1BB) signaling domains in patients with relapsed and/or refractory CD19 or CD20 positive B cell malignancies

Read the detailed description

This is a single center, single arm, open label phase I/1b study to demonstrate the feasibility of manufacturing CAR-T cells expressing tandem receptors against both CD20 and CD19 (CAR-20/19-T) in a completely closed system using the CliniMACS Prodigy device and then determine the safety of this dual targeted CAR in a first-in-human study of patients with relapsed and refractory B cell malignancies. Secondary outcomes will include response rates, and observed toxicities of the treatment, specifically the development of cytokine release syndrome (CRS), an inflammatory storm that has been seen with previous CAR-T therapies.

Being tested
CAR-20/19-T cells (1.0 x10^5 CAR-20/19-T cells/kg), CAR-20/19-T cells (2.5 x10^5 CAR-20/19-T cells/kg), CAR-20/19-T cells (7.5 x10^5 CAR-20/19-T cells/kg), CAR-20/19-T cells (2.5 x10^6 CAR-20/19-T cells/kg)
Keywords
CAR-T, Chimeric antigen receptor T-cell therapy, CAR Therapy
Medical subject headings
Lymphoma, Non-Hodgkin, Lymphoma, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CAR-20/19-T cells (1.0 x10^5 CAR-20/19-T cells/kg)Biological

    CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.

    Phase 1 Dose Level 0: 2.5 x10^5 CAR-20/19-T cells/kg (starting dose level)

  • CAR-20/19-T cells (2.5 x10^5 CAR-20/19-T cells/kg)Biological

    CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.

    Phase 1 Dose Level 1: 7.5 x10^5 CAR-20/19-T cells/kg

  • CAR-20/19-T cells (7.5 x10^5 CAR-20/19-T cells/kg)Biological

    CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.

    Phase 1 Dose Level 2: 2.5 x10^6 CAR-20/19-T cells/kg (goal cell dose)

    Phase 1b Expansion Dose Level: 2.5 x 10^6 cells/kg (single infusion)

  • CAR-20/19-T cells (2.5 x10^6 CAR-20/19-T cells/kg)Biological

    CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.

Study groups in NCT03019055
Study groupRoleWhat they receive
CAR-20/19-T cells (1.0 x10^5 CAR-20/19-T cells/kg)ExperimentalDose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.
Receives: Biological: CAR-20/19-T cells (1.0 x10^5 CAR-20/19-T cells/kg)
CAR-20/19-T cells (2.5 x10^5 CAR-20/19-T cells/kg)ExperimentalDose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.
Receives: Biological: CAR-20/19-T cells (2.5 x10^5 CAR-20/19-T cells/kg)
CAR-20/19-T cells (7.5 x10^5 CAR-20/19-T cells/kg)ExperimentalDose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.
Receives: Biological: CAR-20/19-T cells (7.5 x10^5 CAR-20/19-T cells/kg)
CAR-20/19-T cells (2.5 x10^6 CAR-20/19-T cells/kg)ExperimentalDose Escalation Phase: CAR-20/19-T transduced with a lentiviral vector to express an anti CD19 and anti CD20 tandem receptor coupled to CD3ζ and 4-1BB signaling domains will be administered by IV injection. Patients will receive one of four dose levels based the study protocol. Cells will be given over 2 days, 30% of cells infused on Day 0 and 70% of cells infused on Day 1 in the Phase 1 portion and as a single infusion in the Phase 1b portion.
Receives: Biological: CAR-20/19-T cells (2.5 x10^6 CAR-20/19-T cells/kg)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Adverse Events After CAR 20/19-T Cell Infusion

    This measure is the number of adverse events with grade 3 to 5 severity per Common Terminology Criteria for Adverse Events (ver. 4.03) occurring within the first 28 days following infusion.

    Measured: 28 days after infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jan 2017 (estimated)
  2. Study start16 Oct 2017
  3. Primary completion1 Oct 2019
  4. Study completion24 Aug 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
The study is divided into two phases. Phase 1 and Phase 1b. Phase 1: consists of 2 cohorts; dose escalation and dose expansion. The CAR-T cells were given over 2 days. In the phase 1 portion, there will be a dose escalation cohort to determine the safe CAR-20/19-T cell dose in patients with CLL/SLL and NHL. Once the desired dose has been identified there will be a 6 patient dose expansion phase at the specified dose level. Phase 1b: In the Phase 1b portion of the study, we will test the safety of unfractionated CAR-T cells utilizing the safe dose identified in the phase 1 portion (2.5 x 10\^6 cells/kg).
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03019055
Sponsor's protocol ID
PRO00028724
Status last verified
Jul 2023
First submitted
5 Jan 2017
Last updated
27 Jul 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Zurko JC, Fenske TS, Johnson BD, Bucklan D, Szabo A, Xu H, Chaney K, Hamadani M, Hari P, Shah NN. Long-term outcomes and predictors of early response, late relapse, and survival for patients treated with bispecific LV20.19 CAR T-cells. Am J Hematol. 2022 Dec;97(12):1580-1588. doi: 10.1002/ajh.26718. Epub 2022 Sep 20.

    PubMed 36068950

  • Knight JM, Szabo A, Arapi I, Wu R, Emmrich A, Hackett E, Sauber G, Yim S, Johnson B, Hari P, Schneider D, Dropulic B, Cusatis RN, Cole SW, Hillard CJ, Shah NN. Patient-reported outcomes and neurotoxicity markers in patients treated with bispecific LV20.19 CAR T cell therapy. Commun Med (Lond). 2022 May 12;2(1):49. doi: 10.1038/s43856-022-00116-5. eCollection 2022.

    PubMed 35603278

  • 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.

    PubMed 34515338

  • Shah NN, Johnson BD, Schneider D, Zhu F, Szabo A, Keever-Taylor CA, Krueger W, Worden AA, Kadan MJ, Yim S, Cunningham A, Hamadani M, Fenske TS, Dropulic B, Orentas R, Hari P. Bispecific anti-CD20, anti-CD19 CAR T cells for relapsed B cell malignancies: a phase 1 dose escalation and expansion trial. Nat Med. 2020 Oct;26(10):1569-1575. doi: 10.1038/s41591-020-1081-3. Epub 2020 Oct 5.

    PubMed 33020647

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CAR-20/19-T cells (1.0 x10^5 CAR-20/19-T cells/kg), CAR-20/19-T cells (2.5 x10^5 CAR-20/19-T cells/kg) and CAR-20/19-T cells (7.5 x10^5 CAR-20/19-T cells/kg) in people with Lymphoma, Non-Hodgkin and Lymphoma, B-Cell, run by Medical College of Wisconsin at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Adverse Events After CAR 20/19-T Cell Infusion (time frame: 28 days after infusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03019055, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2023.

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