B-Cell Non-Hodgkin LymphomaPhase 1NCT06879340
Evaluating the Safety and Efficacy of DuoCAR20.19.22-D95 in Adult Patients With Relapsed or Refractory B-cell Malignancies
A Phase 1 study testing DuoCAR20.19.22-D95, Fludarabine (Conditional therapy) and Cyclophosphamide (Conditional therapy) in people with B-Cell Non-Hodgkin Lymphoma and B-cell Acute Lymphoblastic Leukemia, run by University of Kansas Medical Center at 1 site in United States.
Trial summary
This multicenter phase 1 trial with "3 + 3" dose escalation design seeks to examine the feasibility and safety of the administration of autologous T cells that have been modified through the introduction of chimeric antigen receptors targeting the B cell surface antigens CD19/20/22 following administration of a… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- B-Cell Non-Hodgkin Lymphoma, B-cell Acute Lymphoblastic Leukemia
- What is being tested?
- DuoCAR20.19.22-D95, Fludarabine (Conditional therapy) and Cyclophosphamide (Conditional therapy)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Mar 2025to Mar 2040
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability of participant to understand this study, and participant willingness to sign a written informed consent
- Women of childbearing potential must have a negative serum pregnancy test 48 hours prior to the start of preparatory regimen
- Patients must have histologically confirmed aggressive B-Cell NHL or ALL as stated below:
- Patients with relapsed or refractory B-Cell ALL i. Demonstration of one or more antigens of interest (CD19, CD20, CD22) in most recent disease evaluation prior to study entry and within 30 days of study entry.
- Patients with relapsed/refractory disease in blood, marrow, and extramedullary sites including CSF will be eligible when there is immunophenotypic evidence of CD19 and/or CD20 and/or CD22 expression
- Primary refractory disease at study entry defined as: A morphologic complete response has never been achieved prior to study entry.
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- Early first relapse at study entry defined as: Disease recurrence by morphologic assessment after duration of first remission at ≤ 18 months
- Relapsed Refractory disease (first or later relapse) at study entry defined as: Morphologic complete response was not achieved after initiation of a second-line (or later) systemic therapy
- Second or greater relapse at study entry defined as: Any disease recurrence following a second or later complete response (with treatment history including two or more lines of systemic therapy)
- Additional considerations beyond above criteria:
- Patients with relapsed or refractory disease after allogeneic stem cell transplantation must be >100 days from HSCT to be eligible for study participation. Furthermore, post-HSCT immunosuppressive medications must be discontinued for at least 4 weeks prior to study entry
- Prior CAR-T therapy is permissible if ≥ 3 months from therapy completion
- Morphological disease in the bone marrow Note: Morphologic disease is defined as blasts being at least 5% in the bone marrow.
- Histologically confirmed aggressive B cell NHL, including the following types defined by WHO 2008 after 2 or more lines of prior therapy:
- DLBCL not otherwise specified; T cell/histiocyte rich large B cell lymphoma; DLBCL associated with chronic inflammation; Epstein-Barr virus (EBV)+ DLBCL of the elderly; Primary cutaneous DLBCL, leg type; OR ii. Primary mediastinal (thymic) large B cell lymphoma iii. Follicular lymphoma 3b and transformation of follicular lymphoma to DLBCL will also be included iv. High-grade B cell lymphoma v. Chemotherapy-refractory disease, defined as one or more of the following:
- Refractory disease is defined as progressive or stable disease as the best response to the most recent prior therapy or relapse within 12 months of autologous stem cell transplantation. Two prior lines of therapy are required for LBCL eligibility. The second line therapy may be chemotherapy based, autologous stem cell transplantation, or CAR-T.
- Relapsed or refractory disease after allogeneic transplant provided patient is at least 100 days from stem cell transplant at the time of enrollment and off of immunosuppressive medications for at least 4 weeks prior to enrollment
- Patients must have received 2 or more lines of adequate prior therapy including at a minimum:
- anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20- negative and
- an anthracycline containing chemotherapy regimen
- for patients with transformed FL must have received prior chemotherapy for follicular lymphoma and subsequently have chemorefractory disease after transformation to DLBCL vi. Prior CAR T therapy permissible if ≥ 3 months from the therapy vii. At least 1 measurable lesion according to the revised IWG Response Criteria for Malignant Lymphoma (Cheson 2007). Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy C. Relapsed or refractory indolent non-Hodgkin lymphoma i. Histologically confirmed indolent non-Hodgkin lymphoma, including grade 1-3b follicular lymphoma or nodal or extranodal marginal zone lymphoma (both per WHO 2016 classification criteria) ii. Relapsed or refractory disease (per Lugano criteria) after two or more previous lines of therapy, iii. Previous lines of therapy to include an anti-CD20 monoclonal antibody combined with an alkylating agent iv. Prior CAR T therapy permissible if ≥ 3 months from the therapy v. At least 1 measurable lesion according to the revised IWG Response Criteria for Malignant Lymphoma (Cheson 2007). Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy vi. Relapsed or refractory disease after allogeneic transplant provided patient is at least 100 days from stem cell transplant at the time of enrollment and off of immunosuppressive medications for at least 4 weeks prior to enrollment D. Relapsed or Refractory Mantle-Cell Lymphoma i. Histologically confirmed mantle-cell lymphoma with either cyclin D1 overexpression or presence of the translocation (T11:14) ii. Disease that is either relapsed or refractory to at least 2 prior lines of previous regimens for mantle-cell lymphoma iii. Previous therapy must have included anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 monoclonal antibody, and BTK inhibitor therapy
- Prior CAR T therapy permissible if ≥ 3 months from the therapy
- At least 1 measurable lesion according to the revised IWG Response Criteria for Malignant Lymphoma (Cheson 2007). Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy
- Relapsed or refractory disease after allogeneic transplant provided patient is ≥ 3 months from stem cell transplant at the time of enrollment and off of immunosuppressive medications for at least 4 weeks prior to enrollment
- Meet institutional criteria for leukapheresis procedure or have availability of previously- collected and stored leukapheresis product that satisfies minimum requirements
- Eastern cooperative oncology group (ECOG) performance status of 0 to 2.
- Adequate hematologic and organ function NOTE: Patients with established diagnosis of benign neutropenia are eligible to participate with ANC between 1000-1500 if in the opinion of treating physician the trial treatment does not pose excessive risk of infection to the patient.
- Adults ≥ 18 years of age, with no upper limit of age
- Life expectancy >2 months
- ≥ 3 months from prior CAR
- Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence or to use the forms of contraception listed in Child-Bearing Potential/Pregnancy section from the time of signing informed consent to at least 12 months following DuoCAR20.19.22-D95 infusion and until CAR positive viable T cells are no longer present by quantitative polymerase chain reaction (qPCR) on two consecutive tests. Men must agree not to donate sperm for the same time period.
Who cannot join
- Patients with CLL, Richter's transformation, and Burkitt lymphoma
- Active CNS involvement by malignancy - CNS3 disease, i.e., patients with WBC count in CSF ≥5 and having blasts in the CSF in patients with ALL or detection of NHL on CSF by flow cytometry or active CNS involvement on imaging)
- Chemotherapy other than lymphodepleting chemotherapy within 2 weeks of infusion
- Investigational medicinal product within the last 30 days prior to screening Note: Investigational therapies must not be used at any time while on study until the first progression following DuoCAR20.19.22-D95 CAR T infusion.
- The following medications are excluded:
- Steroids: Therapeutic doses of steroids must be stopped > 72 hours prior to leukapheresis and > 72 hours prior to DuoCAR20.19.22-D95 infusion. However, the following physiological replacement doses of steroids are allowed: <12 mg/m2/day hydrocortisone or equivalent
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- Immunosuppression: Any other immunosuppressive medication must be stopped ≥ 2 weeks prior to leukapheresis and ≥ 2 weeks prior to DuoCAR20.19.22-D95 infusion. This could include check point inhibitors (monoclonal antibodies and small molecule modulators).
- Antiproliferative therapies other than lymphodepleting chemotherapy within 2 weeks prior to infusion
- Short acting drugs used to treat leukemia or lymphoma (e.g., tyrosine kinase inhibitors, and hydroxyurea) must be stopped > 72 hour prior to leukapheresis and > 72 hours prior to DuoCAR20.19.22-D95 infusion
- Other cytotoxic drugs, including low dose daily or weekly maintenance chemotherapy, must not be given within 2 weeks prior to leukapheresis and within 2 weeks prior to DuoCAR20.19.22-D95 infusion.
- Antibody use including anti-CD20 therapy within 4 weeks prior to infusion or 5 half-lives of the respective antibody, whichever is longer. Note: Rituximab is excluded within 4 weeks prior to infusion.
- CNS disease prophylaxis or treatment must be stopped > 1 week prior to DuoCAR20.19.22-D95 infusion (e.g., intrathecal methotrexate)
- Prior radiation therapy within 2 weeks of infusion
- Active replication of or prior infection with hepatitis B or active hepatitis C (HCV RNA positive)
- HIV positive patients (excluding false positive HIV test resulting from the viral vector used in prior CAR T)
- Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g., blood culture positive ≤ 72 hours prior to infusion)
- Unstable angina and/or myocardial infarction within 6 months prior to screening
- Previous or concurrent malignancy with the following exceptions:
- Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to study entry)
- In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to the study
- A primary malignancy which has been completely resected and in complete remission for ≥ 5 years
- Simultaneously enrolled in any therapeutic clinical trial (except for long-term follow up studies)
- Current or anticipating use of other anti-neoplastic or investigational agents while participating in this study
- Either diagnosed with a psychiatric illness or under the impact of a social situation that would limit compliance with study requirements in the opinion of the investigator
- Is pregnant or breastfeeding
- Intolerance to the excipients of the cell product
- Cardiac arrhythmia not controlled with medical management
- Active COVID-19 (follow ASTCT guidelines)
- Presence of active grade 2 to 4 acute, extensive chronic graft-versus-host disease (GVHD) or that require systemic steroids
- Patients with active neurological auto immune or inflammatory disorders (e.g., Guillain-Barré Syndrome, Amyotrophic Lateral Sclerosis)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Kansas Cancer Center
Westwood, Kansas, 66205
Nurse Navigation, 913-945-7552, CTNurseNav@kumc.edu
Joseph McGuirk, DO
About this study
Official title: A Phase 1 Multicenter, Open Label Trial Evaluating the Safety and Efficacy of DuoCAR20.19.22-D95 in Adult Patients With Relapsed or Refractory B-cell Malignancies
This multicenter phase 1 trial with "3 + 3" dose escalation design seeks to examine the feasibility and safety of the administration of autologous T cells that have been modified through the introduction of chimeric antigen receptors targeting the B cell surface antigens CD19/20/22 following administration of a chemotherapy lymphodepletion regimen in adults with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) or Non-Hodgkin's lymphoma (NHL). The overall goals of this study are to estimate maximum tolerated dose (MTD) level, establish the overall safety profile and evaluate initial efficacy of administering duo-CAR-T cell treatment in this patient population.
Read the detailed description
Dose Escalation Cohort (Phase 1)
This will have 3 enrollment groups:
Group A: Participants with B-ALL (CAR pre-treated or CAR naïve), Group B: Participants with B-NHL (CAR pre-treated), Group C: Participants with B-NHL (CAR naïve)
The trial will begin with a phase I dose escalation evaluation in each of the three enrollment groups. Participants will be treated either at dose level 1 and dose level -1 or at dose level 1 and dose level 2 of CAR T cells. This phase will determine the MTD and /or RP2D for the subsequent Phase 2 study. The trial duration for an individual participant is 15 years from DUOCAR20.19.22-D95-CAR T cell infusion. Following infusion, DLT assessments will continue through end of Day 30 visit during Dose Escalation Phase 1. Efficacy and routine safety monitoring for Phase 1 cohort will occur at established protocol-defined intervals through Year 2 or until the start of a new treatment regimen, whichever occurs sooner. The observational long-term follow-up portion of the study will then become operative.
- Being tested
- DuoCAR20.19.22-D95, Fludarabine (Conditional therapy), Cyclophosphamide (Conditional therapy)
- Medical subject headings
- Lymphoma, B-Cell, Burkitt Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DuoCAR20.19.22-D95Drug
Patient derived autologous T cells, lentiviral transduced to generate, using the Miltenyi CliniMACS Prodigy® closed transduction system, a Duo-CAR-T cells targeting cell surface antigens CD19/20/22.
Fludarabine (Conditional therapy)Drug
Lymphodepletion chemotherapy
Cyclophosphamide (Conditional therapy)Drug
Lymphodepletion chemotherapy
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 (Dose Escalation) | Experimental | Lymphodepletion:
Fludarabine: Days -6 to -3 (4 days total) Cyclophosphamide: Days -6 and -5 (2 days total)
Investigational Treatment:
DuoCAR20.19.22-D95 will be infused on day # 0
Patients will receive lymphodepletion chemotherapy and receive the CAR T cell infusion on day 0 (or up to day +14 in extenuating clinical conditions). Patients will be hospitalized inpatient period of at least 7 days from the day of the CAR T infusion. Receives: Drug: DuoCAR20.19.22-D95; Drug: Fludarabine (Conditional therapy); Drug: Cyclophosphamide (Conditional therapy) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
The MTD is defined as the dose level immediately below that in which ≥ 2/6 participants experience a dose limiting toxicity (DLT).
Measured: Approximately 30 days
Recommended Phase 2 Dose (RP2D)
Determine using MTD and DLTs.
Measured: Approximately 30 days
Safety: Incidence of Serious Adverse Events/Adverse Events
Toxicities of DuoCAR20.19.22-D95 in combination with preceding lymphodepleting chemotherapy regimen As measured with CTCAE v 5.0,
Measured: Approximately 30 days
Treatment-related Mortality (TRM)
defined by the absence of progressive disease at the time of death.
Measured: Approximately 1 year
Presence of replication competent lentivirus (RCL) in peripheral blood samples
Measured with qPCR
Measured: Approximately 15 years
Secondary outcomes (8)
Efficacy of DuoCAR 20.19.22-D95
Overall response rate defined by CR/PR rate as determined by WHO defined bone marrow results in ALL and the Lugano response criteria in B-cell NHL.
Measured: up to 24 months
Safety related to DuoCAR20.19.22-D95
To assess long-term safety risks, per FDA guidelines pertaining to gene therapy, as measured by delayed adverse events of special interest potentially related to DuoCAR20.19.22-D95
Measured: Approximately 15 years
Pharmacology (Expansion kinetics)
Expansion kinetics of DuoCAR20.19.22-D95 over time as measured by PCR and/or flow cytometry, WinNonlin 8.4
Measured: 28 days
Manufacturing Feasibility of Miltenyi CliniMACS Prodigy (By number of participants)
To assess the Miltenyi CliniMACS Prodigy® closed transduction system for manufacturing feasibility of DuoCAR20.19.22-D95 throughout dose escalation and efficacy. For evaluation of feasibility, the number of participants which can successfully manufacture the targeted dose number will be determined and reported by dose level for the three enrollment groups.
Measured: 2 weeks
Blood DuoCAR20.19.22-D95 concentrations (PCR)
determined by PCR and/or flow cytometry
Measured: approximately 2 years
Blood DuoCAR20.19.22-D95 concentrations (Non-parametric PK parameters)
Non-parametric pharmacokinetic data analysis will be performed on resultant blood DuoCAR20.19.22-D95 concentration-time data using WinNonlin 8.4.
Measured: approximately 2 years
Blood DuoCAR20.19.22-D95 concentrations (time data)
The frequency (n,%) of observed concentrations below the lower limit of quantitation (LLOQ), reported as zero, will be described for each sampling timepoint
Measured: approximately 2 years
Blood DuoCAR20.19.22-D95 mean concentrations
Mean concentrations will be provided for blood DuoCAR20.19.22-D95 concentration-time data
Measured: approximately 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2025
- Study start31 Mar 2025
- Primary completionMar 2030 (estimated)
- Study completionMar 2040 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (62)Papers the sponsor has linked to this study.
- Other trials for B-Cell Non-Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by University of Kansas Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Kansas Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Joseph McGuirk, University of Kansas Medical Center
- Investigators
- Joseph McGuirk, D.O., Principal investigator, University of Kansas Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06879340
- Sponsor's protocol ID
- STUDY00161006
- Status last verified
- May 2026
- First submitted
- 3 Mar 2025
- Last updated
- 14 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Dioverti V, Boghdadly ZE, Shahid Z, Waghmare A, Abidi MZ, Pergam S, Boeckh M, Dadwal S, Kamboj M, Seo S, Chemaly RF, Papanicolaou GA. Revised Guidelines for Coronavirus Disease 19 Management in Hematopoietic Cell Transplantation and Cellular Therapy Recipients (August 2022). Transplant Cell Ther. 2022 Dec;28(12):810-821. doi: 10.1016/j.jtct.2022.09.002. Epub 2022 Sep 11.
PubMed 36103987Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S, Go WY, Eldjerou L, Gardner RA, Frey N, Curran KJ, Peggs K, Pasquini M, DiPersio JF, van den Brink MRM, Komanduri KV, Grupp SA, Neelapu SS. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019 Apr;25(4):625-638. doi: 10.1016/j.bbmt.2018.12.758. Epub 2018 Dec 25.
PubMed 30592986Wierda W, O'Brien S, Wen S, Faderl S, Garcia-Manero G, Thomas D, Do KA, Cortes J, Koller C, Beran M, Ferrajoli A, Giles F, Lerner S, Albitar M, Kantarjian H, Keating M. Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia. J Clin Oncol. 2005 Jun 20;23(18):4070-8. doi: 10.1200/JCO.2005.12.516. Epub 2005 Mar 14.
PubMed 15767647Hedger MP, Meinhardt A. Local regulation of T cell numbers and lymphocyte-inhibiting activity in the interstitial tissue of the adult rat testis. J Reprod Immunol. 2000 Oct-Nov;48(2):69-80. doi: 10.1016/s0165-0378(00)00071-1.
PubMed 11011073Muller SM, Ege M, Pottharst A, Schulz AS, Schwarz K, Friedrich W. Transplacentally acquired maternal T lymphocytes in severe combined immunodeficiency: a study of 121 patients. Blood. 2001 Sep 15;98(6):1847-51. doi: 10.1182/blood.v98.6.1847.
PubMed 11535520Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. doi: 10.1200/JCO.2006.09.2403. Epub 2007 Jan 22.
PubMed 17242396Barrington SF, Mikhaeel NG, Kostakoglu L, Meignan M, Hutchings M, Mueller SP, Schwartz LH, Zucca E, Fisher RI, Trotman J, Hoekstra OS, Hicks RJ, O'Doherty MJ, Hustinx R, Biggi A, Cheson BD. Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. J Clin Oncol. 2014 Sep 20;32(27):3048-58. doi: 10.1200/JCO.2013.53.5229.
PubMed 25113771Pulsipher MA, Han X, Maude SL, Laetsch TW, Qayed M, Rives S, Boyer MW, Hiramatsu H, Yanik GA, Driscoll T, Myers GD, Bader P, Baruchel A, Buechner J, Stefanski HE, Kalfoglou C, Nguyen K, Waldron ER, Thudium Mueller K, Maier HJ, Kari G, Grupp SA. Next-Generation Sequencing of Minimal Residual Disease for Predicting Relapse after Tisagenlecleucel in Children and Young Adults with Acute Lymphoblastic Leukemia. Blood Cancer Discov. 2022 Jan;3(1):66-81. doi: 10.1158/2643-3230.BCD-21-0095. Epub 2021 Dec 1.
PubMed 35019853Rossoff J, Baggott C, Prabhu S, Pacenta H, Phillips CL, Stefanski H, Talano JA, Moskop A, Margossian SP, Verneris MR, Myers GD, Karras N, Brown PA, Qayed M, Hermiston M, Satwani P, Krupski C, Keating AK, Wilcox R, Rabik CA, Fabrizio VA, Kunicki M, Chinnabhandar V, Goksenin AY, Curran KJ, Mackall CL, Laetsch TW, Schultz LM. Out-of-specification tisagenlecleucel does not compromise safety or efficacy in pediatric acute lymphoblastic leukemia. Blood. 2021 Nov 25;138(21):2138-2142. doi: 10.1182/blood.2021012392. No abstract available.
PubMed 34499715Laetsch TW, Myers GD, Baruchel A, Dietz AC, Pulsipher MA, Bittencourt H, Buechner J, De Moerloose B, Davis KL, Nemecek E, Driscoll T, Mechinaud F, Boissel N, Rives S, Bader P, Peters C, Sabnis HS, Grupp SA, Yanik GA, Hiramatsu H, Stefanski HE, Rasouliyan L, Yi L, Shah S, Zhang J, Harris AC. Patient-reported quality of life after tisagenlecleucel infusion in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukaemia: a global, single-arm, phase 2 trial. Lancet Oncol. 2019 Dec;20(12):1710-1718. doi: 10.1016/S1470-2045(19)30493-0. Epub 2019 Oct 9.
PubMed 31606419Gardner RA, Finney O, Annesley C, Brakke H, Summers C, Leger K, Bleakley M, Brown C, Mgebroff S, Kelly-Spratt KS, Hoglund V, Lindgren C, Oron AP, Li D, Riddell SR, Park JR, Jensen MC. Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Blood. 2017 Jun 22;129(25):3322-3331. doi: 10.1182/blood-2017-02-769208. Epub 2017 Apr 13.
PubMed 28408462Schneider D, Xiong Y, Wu D, Hu P, Alabanza L, Steimle B, Mahmud H, Anthony-Gonda K, Krueger W, Zhu Z, Dimitrov DS, Orentas RJ, Dropulic B. Trispecific CD19-CD20-CD22-targeting duoCAR-T cells eliminate antigen-heterogeneous B cell tumors in preclinical models. Sci Transl Med. 2021 Mar 24;13(586):eabc6401. doi: 10.1126/scitranslmed.abc6401.
PubMed 33762438Dekker L, Calkoen FG, Jiang Y, Blok H, Veldkamp SR, De Koning C, Spoon M, Admiraal R, Hoogerbrugge P, Vormoor B, Vormoor HJ, Visscher H, Bierings M, Van Der Vlugt M, Van Tinteren H, Nijstad AL, Huitema ADR, Van Der Elst KCM, Pieters R, Lindemans CA, Nierkens S. Fludarabine exposure predicts outcome after CD19 CAR T-cell therapy in children and young adults with acute leukemia. Blood Adv. 2022 Apr 12;6(7):1969-1976. doi: 10.1182/bloodadvances.2021006700.
PubMed 35134115Rogers PR, Song J, Gramaglia I, Killeen N, Croft M. OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4 T cells. Immunity. 2001 Sep;15(3):445-55. doi: 10.1016/s1074-7613(01)00191-1.
PubMed 11567634Gramaglia I, Jember A, Pippig SD, Weinberg AD, Killeen N, Croft M. The OX40 costimulatory receptor determines the development of CD4 memory by regulating primary clonal expansion. J Immunol. 2000 Sep 15;165(6):3043-50. doi: 10.4049/jimmunol.165.6.3043.
PubMed 10975814
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Multicenter, Open Label Trial Evaluating the Safety and Efficacy of DuoCAR20.19.22-D95 in Adult Patients With Relapsed or Refractory B-cell Malignancies
- ClinicalTrials.gov ID
- NCT06879340
- Acronym / sponsor ID
- STUDY00161006
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- University of Kansas Medical CenterUniversity, hospital or other
- Study start
- 31 Mar 2025 (actual)
- Primary completion
- Mar 2030 (estimated)
- Study completion
- Mar 2040 (estimated)
- First posted
- 17 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This multicenter phase 1 trial with "3 + 3" dose escalation design seeks to examine the feasibility and safety of the administration of autologous T cells that have been modified through the introduction of chimeric antigen receptors targeting the B cell surface antigens CD19/20/22 following administration of a chemotherapy lymphodepletion regimen in adults with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) or Non-Hodgkin's lymphoma (NHL). The overall goals of this study are to estimate maximum tolerated dose (MTD) level, establish the overall safety profile and evaluate initial efficacy of administering duo-CAR-T cell treatment in this patient population.
Detailed description
Dose Escalation Cohort (Phase 1)
This will have 3 enrollment groups:
Group A: Participants with B-ALL (CAR pre-treated or CAR naïve), Group B: Participants with B-NHL (CAR pre-treated), Group C: Participants with B-NHL (CAR naïve)
The trial will begin with a phase I dose escalation evaluation in each of the three enrollment groups. Participants will be treated either at dose level 1 and dose level -1 or at dose level 1 and dose level 2 of CAR T cells. This phase will determine the MTD and /or RP2D for the subsequent Phase 2 study. The trial duration for an individual participant is 15 years from DUOCAR20.19.22-D95-CAR T cell infusion. Following infusion, DLT assessments will continue through end of Day 30 visit during Dose Escalation Phase 1. Efficacy and routine safety monitoring for Phase 1 cohort will occur at established protocol-defined intervals through Year 2 or until the start of a new treatment regimen, whichever occurs sooner. The observational long-term follow-up portion of the study will then become operative.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Phase 1 (Dose Escalation) | Experimental | Drug: DuoCAR20.19.22-D95, Drug: Fludarabine (Conditional therapy), Drug: Cyclophosphamide (Conditional therapy)Lymphodepletion: Fludarabine: Days -6 to -3 (4 days total) Cyclophosphamide: Days -6 and -5 (2 days total) Investigational Treatment: DuoCAR20.19.22-D95 will be infused on day # 0 Patients will receive lymphodepletion chemotherapy and receive the CAR T cell infusion on day 0 (or up to day +14 in extenuating clinical conditions). Patients will be hospitalized inpatient period of at least 7 days from the day of the CAR T infusion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- Ability of participant to understand this study, and participant willingness to sign a written informed consent
- Women of childbearing potential must have a negative serum pregnancy test 48 hours prior to the start of preparatory regimen
- Patients must have histologically confirmed aggressive B-Cell NHL or ALL as stated below:
- Prior CAR T therapy permissible if ≥ 3 months from the therapy
- At least 1 measurable lesion according to the revised IWG Response Criteria for Malignant Lymphoma (Cheson 2007). Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy
Key exclusion criteria (30 listed)
- Patients with CLL, Richter's transformation, and Burkitt lymphoma
- Active CNS involvement by malignancy - CNS3 disease, i.e., patients with WBC count in CSF ≥5 and having blasts in the CSF in patients with ALL or detection of NHL on CSF by flow cytometry or active CNS involvement on imaging)
- Chemotherapy other than lymphodepleting chemotherapy within 2 weeks of infusion
- Investigational medicinal product within the last 30 days prior to screening Note: Investigational therapies must not be used at any time while on study until the first progression following DuoCAR20.19.22-D95 CAR T infusion.
- The following medications are excluded:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DuoCAR20.19.22-D95Patient derived autologous T cells, lentiviral transduced to generate, using the Miltenyi CliniMACS Prodigy® closed transduction system, a Duo-CAR-T cells targeting cell surface antigens CD19/20/22. | Drug | Phase 1 (Dose Escalation) |
| Fludarabine (Conditional therapy)Lymphodepletion chemotherapy | Drug | Phase 1 (Dose Escalation) |
| Cyclophosphamide (Conditional therapy)Lymphodepletion chemotherapy | Drug | Phase 1 (Dose Escalation) |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: Approximately 30 days
The MTD is defined as the dose level immediately below that in which ≥ 2/6 participants experience a dose limiting toxicity (DLT).
Recommended Phase 2 Dose (RP2D)
Time frame: Approximately 30 days
Determine using MTD and DLTs.
Safety: Incidence of Serious Adverse Events/Adverse Events
Time frame: Approximately 30 days
Toxicities of DuoCAR20.19.22-D95 in combination with preceding lymphodepleting chemotherapy regimen As measured with CTCAE v 5.0,
Treatment-related Mortality (TRM)
Time frame: Approximately 1 year
defined by the absence of progressive disease at the time of death.
Presence of replication competent lentivirus (RCL) in peripheral blood samples
Time frame: Approximately 15 years
Measured with qPCR
8 secondary outcomes
Efficacy of DuoCAR 20.19.22-D95
Time frame: up to 24 months
Safety related to DuoCAR20.19.22-D95
Time frame: Approximately 15 years
Pharmacology (Expansion kinetics)
Time frame: 28 days
Manufacturing Feasibility of Miltenyi CliniMACS Prodigy (By number of participants)
Time frame: 2 weeks
Blood DuoCAR20.19.22-D95 concentrations (PCR)
Time frame: approximately 2 years
Blood DuoCAR20.19.22-D95 concentrations (Non-parametric PK parameters)
Time frame: approximately 2 years
Blood DuoCAR20.19.22-D95 concentrations (time data)
Time frame: approximately 2 years
Blood DuoCAR20.19.22-D95 mean concentrations
Time frame: approximately 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2026.
- Background: PubMed 36103987Dioverti V, Boghdadly ZE, Shahid Z, Waghmare A, Abidi MZ, Pergam S, Boeckh M, Dadwal S, Kamboj M, Seo S, Chemaly RF, Papanicolaou GA. Revised Guidelines for Coronavirus Disease 19 Management in Hematopoietic Cell Transplantation and Cellular Therapy Recipients (August 2022). Transplant Cell Ther. 2022 Dec;28(12):810-821. doi: 10.1016/j.jtct.2022.09.002. Epub 2022 Sep 11.
- Background: PubMed 30592986Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S, Go WY, Eldjerou L, Gardner RA, Frey N, Curran KJ, Peggs K, Pasquini M, DiPersio JF, van den Brink MRM, Komanduri KV, Grupp SA, Neelapu SS. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019 Apr;25(4):625-638. doi: 10.1016/j.bbmt.2018.12.758. Epub 2018 Dec 25.
- Background: PubMed 15767647Wierda W, O'Brien S, Wen S, Faderl S, Garcia-Manero G, Thomas D, Do KA, Cortes J, Koller C, Beran M, Ferrajoli A, Giles F, Lerner S, Albitar M, Kantarjian H, Keating M. Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia. J Clin Oncol. 2005 Jun 20;23(18):4070-8. doi: 10.1200/JCO.2005.12.516. Epub 2005 Mar 14.
- Background: PubMed 11011073Hedger MP, Meinhardt A. Local regulation of T cell numbers and lymphocyte-inhibiting activity in the interstitial tissue of the adult rat testis. J Reprod Immunol. 2000 Oct-Nov;48(2):69-80. doi: 10.1016/s0165-0378(00)00071-1.
- Background: PubMed 11535520Muller SM, Ege M, Pottharst A, Schulz AS, Schwarz K, Friedrich W. Transplacentally acquired maternal T lymphocytes in severe combined immunodeficiency: a study of 121 patients. Blood. 2001 Sep 15;98(6):1847-51. doi: 10.1182/blood.v98.6.1847.
- Background: PubMed 17242396Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. doi: 10.1200/JCO.2006.09.2403. Epub 2007 Jan 22.
- Background: PubMed 25113771Barrington SF, Mikhaeel NG, Kostakoglu L, Meignan M, Hutchings M, Mueller SP, Schwartz LH, Zucca E, Fisher RI, Trotman J, Hoekstra OS, Hicks RJ, O'Doherty MJ, Hustinx R, Biggi A, Cheson BD. Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. J Clin Oncol. 2014 Sep 20;32(27):3048-58. doi: 10.1200/JCO.2013.53.5229.
- Background: PubMed 35019853Pulsipher MA, Han X, Maude SL, Laetsch TW, Qayed M, Rives S, Boyer MW, Hiramatsu H, Yanik GA, Driscoll T, Myers GD, Bader P, Baruchel A, Buechner J, Stefanski HE, Kalfoglou C, Nguyen K, Waldron ER, Thudium Mueller K, Maier HJ, Kari G, Grupp SA. Next-Generation Sequencing of Minimal Residual Disease for Predicting Relapse after Tisagenlecleucel in Children and Young Adults with Acute Lymphoblastic Leukemia. Blood Cancer Discov. 2022 Jan;3(1):66-81. doi: 10.1158/2643-3230.BCD-21-0095. Epub 2021 Dec 1.
- Background: PubMed 34499715Rossoff J, Baggott C, Prabhu S, Pacenta H, Phillips CL, Stefanski H, Talano JA, Moskop A, Margossian SP, Verneris MR, Myers GD, Karras N, Brown PA, Qayed M, Hermiston M, Satwani P, Krupski C, Keating AK, Wilcox R, Rabik CA, Fabrizio VA, Kunicki M, Chinnabhandar V, Goksenin AY, Curran KJ, Mackall CL, Laetsch TW, Schultz LM. Out-of-specification tisagenlecleucel does not compromise safety or efficacy in pediatric acute lymphoblastic leukemia. Blood. 2021 Nov 25;138(21):2138-2142. doi: 10.1182/blood.2021012392. No abstract available.
- Background: PubMed 31606419Laetsch TW, Myers GD, Baruchel A, Dietz AC, Pulsipher MA, Bittencourt H, Buechner J, De Moerloose B, Davis KL, Nemecek E, Driscoll T, Mechinaud F, Boissel N, Rives S, Bader P, Peters C, Sabnis HS, Grupp SA, Yanik GA, Hiramatsu H, Stefanski HE, Rasouliyan L, Yi L, Shah S, Zhang J, Harris AC. Patient-reported quality of life after tisagenlecleucel infusion in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukaemia: a global, single-arm, phase 2 trial. Lancet Oncol. 2019 Dec;20(12):1710-1718. doi: 10.1016/S1470-2045(19)30493-0. Epub 2019 Oct 9.
- Background: PubMed 28408462Gardner RA, Finney O, Annesley C, Brakke H, Summers C, Leger K, Bleakley M, Brown C, Mgebroff S, Kelly-Spratt KS, Hoglund V, Lindgren C, Oron AP, Li D, Riddell SR, Park JR, Jensen MC. Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Blood. 2017 Jun 22;129(25):3322-3331. doi: 10.1182/blood-2017-02-769208. Epub 2017 Apr 13.
- Background: PubMed 33762438Schneider D, Xiong Y, Wu D, Hu P, Alabanza L, Steimle B, Mahmud H, Anthony-Gonda K, Krueger W, Zhu Z, Dimitrov DS, Orentas RJ, Dropulic B. Trispecific CD19-CD20-CD22-targeting duoCAR-T cells eliminate antigen-heterogeneous B cell tumors in preclinical models. Sci Transl Med. 2021 Mar 24;13(586):eabc6401. doi: 10.1126/scitranslmed.abc6401.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Joseph McGuirk, D.O. principal investigator
University of Kansas Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DuoCAR20.19.22-D95, Fludarabine (Conditional therapy) and Cyclophosphamide (Conditional therapy) in people with B-Cell Non-Hodgkin Lymphoma and B-cell Acute Lymphoblastic Leukemia, run by University of Kansas Medical Center 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 31 inclusion and 30 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: looking for participants now, as of the sponsor's last update on 14 May 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) (time frame: Approximately 30 days). The study lists 5 primary outcomes in all. 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 NCT06879340, which also lists 62 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 14 May 2026.