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Chronic Lymphocytic LeukemiaPhase 1/2NCT03960840

Phase I/II Study of Rapcabtagene Autoleucel in CLL, 3L+ DLBCL, r/r ALL and 1L HR LBCL

A Phase 1/2 study testing Rapcabtagene autoleucel single agent and Ibrutinib in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Novartis Pharmaceuticals at 37 sites in 8 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This is a phase I/II study to evaluate the feasibility, safety and preliminary antitumor efficacy of rapcabtagene autoleucel (also known as YTB323). Rapcabtagene autoleucel will be investigated in combination with ibrutinib in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and as single agent in… Read more about this study

Who is it for?
Ages 18 to 100 years
What is being tested?
Rapcabtagene autoleucel single agent and Ibrutinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
218 participants
Where
37 sitesin 8 countries
Study dates
26 Jun 2019to 24 Jul 2027
Phase
Phase 1/2
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 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ECOG performance status 0-1 for ALL and DLBCL
  • ECOG performance status 0-2 for 1L HR LBCL at screening
  • CLL or SLL diagnosis according to iwCLL criteria
  • CLL/SLL in SD or PR after at least 6 months of ibrutinib, either as second or subsequent line of therapy
  • DLBCL diagnosis by local histopathology
  • DLBCL relapsed or refractory after 2 or more lines of therapy, including autologous hematopoietic stem cell transplantation (HSCT)
Show all 13Show fewer
  • Refractory or relapsed CD19-positive ALL
  • ALL with morphologic disease in the bone marrow
  • 1L HR LBCL - Considered to be high-risk based on at least 1 of the following at diagnosis:
  • IPI score of 3, 4 or 5
  • MYC and BCL2 and/or BCL6 rearrangement (DH/TH lymphoma)
  • Participants must have received 2 cycles of frontline therapy for LBCL with R-CHOP or Pola-R-CHP or DA-EPOCH-R. Participants with DH/TH lymphoma must have received at least one cycle (the most recent) DA-EPOCH-R.
  • Participants must have a positive PET per Lugano classification (Deauville PET score of 4 or 5 and an overall response of PR/SD) after 2 cycles of frontline CIT. Note: Patient's with Deauville PET score of 5 and overall response of PD, or with Deauville PET score of 1, 2, or 3 and overall response of CR, are not eligible for this trial.

Who cannot join

  • Prior CD19-directed therapy
  • Prior administration of a genetically engineered cellular product
  • Prior allogeneic HSCT
  • Richter's transformation
  • For 1L HR LBCL: Richter's transformation, Burkitt lymphoma, primary DLBCL of CNS, DLBCL associated with chronic inflammation, intravascular large B-cell lymphoma, ALK- positive large B-cell lymphoma, HHV8 positive LBCL, DLBCL leg type or EBV positive DLBCL, NOS.
  • Active CNS lymphoma
Show all 9Show fewer
  • For 1L HR LBCL: Active or prior history CNS involvement by malignancy
  • Targeted small molecule or kinase inhibitor within 2 weeks from leukapheresis
  • Other protocol-defined inclusion/exclusion may apply.

Trial locations and contacts

37 sites in 8 countries.

37 sites in 8 countries

United States12 sites

  • St Davids South Austin Medical Ctr

    Austin, Texas, 78704

  • Mass Gen Hosp Cancer Center

    Boston, Massachusetts, 02114

  • Uni of Chi Medi Ctr Hema and Onco

    Chicago, Illinois, 60637

  • Uni Of TX MD Anderson Cancer Cntr

    Houston, Texas, 77030

  • University of California LA

    Los Angeles, California, 90095

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Tennessee Oncology

    Nashville, Tennessee, 37203

  • University of Pennsylvania Clinical

    Philadelphia, Pennsylvania, 19104

  • Sarah Cannon Research Institute

    San Antonio, Texas, 78229

  • Stanford University Medical Center

    Stanford, California, 94305-5826

  • H Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

  • University of Kansas Cancer Center

    Westwood, Kansas, 66205

Other trials in United States

Spain10 sites

  • Novartis Investigative Site

    Badalona, Barcelona, 08916

  • Novartis Investigative Site

    Barcelona, 08035

  • Novartis Investigative Site

    Barcelona, 08041

  • Novartis Investigative Site

    Córdoba, 14004

  • Novartis Investigative Site

    L'Hospitalet de Llobregat, Barcelona, 08907

  • Novartis Investigative Site

    Madrid, 28009

  • Novartis Investigative Site

    Madrid, 28041

  • Novartis Investigative Site

    Salamanca, 37007

  • Novartis Investigative Site

    Seville, 41013

  • Novartis Investigative Site

    Valencia, 46010

Other trials in Spain

France4 sites

  • Novartis Investigative Site

    Marseille, 13273

  • Novartis Investigative Site

    Paris, 75475

  • Novartis Investigative Site

    Pierre-Bénite, 69495

  • Novartis Investigative Site

    Rennes, 35033

Other trials in France

Italy3 sites

  • Novartis Investigative Site

    Bergamo, BG, 24127

  • Novartis Investigative Site

    Milan, MI, 20132

  • Novartis Investigative Site

    Rozzano, MI, 20089

Other trials in Italy

Japan3 sites

  • Novartis Investigative Site

    Bunkyo Ku, Tokyo, 1138677

  • Novartis Investigative Site

    Fukuoka, 8128582

  • Novartis Investigative Site

    Sapporo, Hokkaido, 0608648

Other trials in Japan

Australia2 sites

  • Novartis Investigative Site

    Melbourne, Victoria, 3000

  • Novartis Investigative Site

    Melbourne, Victoria, 3004

Other trials in Australia

Germany2 sites

  • Novartis Investigative Site

    Frankfurt am Main, Hesse, 60590

  • Novartis Investigative Site

    Leipzig, Saxony, 04103

Other trials in Germany

Austria1 site

  • Novartis Investigative Site

    Vienna, 1090

Other trials in Austria

About this study

Official title: Phase I/II, Open Label, Multicenter Study of Rapcabtagene Autoleucel in Adult Patients With CLL/SLL, 3L+ DLBCL, r/r ALL and 1L HR LBCL

This is a phase I/II study to evaluate the feasibility, safety and preliminary antitumor efficacy of rapcabtagene autoleucel (also known as YTB323). Rapcabtagene autoleucel will be investigated in combination with ibrutinib in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and as single agent in diffuse large B-cell lymphoma (3L+ DLBCL), adult acute lymphoblastic leukemia (ALL) and 1st Line High Risk Large B-Cell Lymphoma (1L HR LBCL).

Read the detailed description

This clinical trial is phase I/II open label, multi-center study of rapcabtagene autoleucel.

The Phase I part of the study comprises three independent treatment arms:

  • Rapcabtagene autoleucel in combination with ibrutinib in adult CLL/SLL participants with SD or PR after at least 6 months of second or subsequent line ibrutinib therapy. As of 05-May-2021, this arm had completed enrollment.
  • Rapcabtagene autoleucel single agent in adult DLBCL participants having failed two or more lines of chemotherapy and either having progressed (or relapsed) after autologous HSCT or being ineligible for or not consenting to the procedure.
  • Rapcabtagene autoleucel single agent in adult relapsed/refractory ALL participants

The Phase II part of the study comprises two independent cohorts:

  • Rapcabtagene autoleucel single agent in adult 3L + DLBCL participants having failed two or more lines of chemoimmunotherapy and either having progressed (or relapsed) after autologous HSCT or being ineligible for or not consenting to the procedure. This is an extension of the Phase I r/r DLBCL treatment arm to support Phase II objectives
  • Rapcabtagene autoleucel single agent in newly diagnosed, adult 1L HR LBCL participants defined as IPI 3-5 and/or DH/TH disease who have completed 2 cycles of CIT and have a response of PR/SD (with a Deauville score of 4-5).

In the Phase I part of the trial, the 3L+ DLBCL and ALL arms consist of two parts: a dose escalation part to evaluate feasibility, characterize safety and identify the recommended dose (RD) of rapcabtagene autoleucel, and may be followed by a dose expansion part to further characterize safety, study rapcabtagene autoleucel cellular kinetics and assess preliminary antitumor activity. Once the RD of rapcabtagene autoleucel is determined for each arm, the corresponding expansion part may commence.

In the Phase II part of the trial, approximately 70 additional participants will be enrolled in a 3L+ DLBCL cohort treated at the recommended dose (RD). Including the 3L+ DLBCL participants who were treated at the RD from the Phase I part, it is planned to have in total a cohort of approximately 100 participants included in the primary efficacy analysis based on the efficacy analysis set. In addition, a separate cohort in 1LHR LBCL will be included, with approximately 50-60 participants planned for the primary efficacy analysis based on the efficacy analysis set.

Participants will be followed under the current treatment protocol for safety and efficacy within this trial for a minimum of 2 years before being transferred to the long-term follow-up trial. Once the study is complete, participants will be enrolled in a post-study long term follow-up for lentiviral vector safety for up to 15 years. This post-study long term follow-up for lentiviral vector safety will continue under a separate destination protocol.

Being tested
Rapcabtagene autoleucel single agent, Ibrutinib
Keywords
CAR-T, Ibrutinib, CLL, DLBCL, ALL, BLRM, YTB323, Rapcabtagene autoleucel
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Large B-Cell, Diffuse, Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

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

  • Rapcabtagene autoleucel single agentBiological

    Single infusion of rapcabtagene autoleucel

  • IbrutinibDrug

    Tablets or capsules for oral daily use

Study groups in NCT03960840
Study groupRoleWhat they receive
CLL/SLLExperimentalDose escalation of rapcabtagene autoleucel in combination with ibrutinib
Receives: Biological: Rapcabtagene autoleucel single agent; Drug: Ibrutinib
3L+ DLBCLExperimentalDose escalation and expansion of rapcabtagene autoleucel single agent in 3L+ DLBCL
Receives: Biological: Rapcabtagene autoleucel single agent
Adult ALLExperimentalDose escalation of rapcabtagene autoleucel single agent in adult ALL
Receives: Biological: Rapcabtagene autoleucel single agent
1L HR LBCLExperimentalRapcabtagene autoleucel single agent in 1L HR LBCL
Receives: Biological: Rapcabtagene autoleucel single agent

What is being measured

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

  1. Phase 1: Dose recommendation: Incidence and nature of Dose Limiting Toxicities (Dose Escalation part only)

    Measured: 28 days

  2. Phase 1: Safety: Incidence and severity of AEs and SAEs, including changes in laboratory values, ECG and vital signs

    Measured: 24 months

  3. Phase 1: Tolerability: Ibrutinib dose modifications in the CLL/SLL arm

    Measured: 24 months

  4. Phase 1: Manufacture success: Number of patients infused with planned target dose

    Measured: 24 months

  5. Phase 2: Complete Response Rate (CRR) as assessed by local Investigator

    CRR defined as best overall response (BOR) of CR after rapcabtagene autoleucel infusion as per Lugano criteria for 3L+ Diffuse Large B-Cell Lymphoma (DLBCL) and 1L High Risk Large B-Cell (HR LBCL)

    Measured: 24 months

Secondary outcomes (29)

  1. Phase 1: Complete Response (CR)/Partial Response (CR) in CLL/SLL

    per international workshop on Chronic Lymphocytic Leukemia (iwCLL) response criteria

    Measured: 24 months

  2. Phase 1: BOR of CR/PR per Lugano criteria in 3L+ DLBCL

    Measured: 24 months

  3. Phase 1: Duration of response (DOR) in CLL/SLL and 3L+ DLBCL

    DOR as assessed by time from first achievement of CR/PR after rapcabtagene autoleucel infusion until first documented disease progression or death due to any cause

    Measured: 24 months

  4. Phase 1: BOR in ALL as assessed by an Independent Review Committee (IRC)

    BOR of CR/CRi by 3 months after rapcabtagene autoleucel infusion as per IRC assessment.

    Measured: month 3

  5. Phase 1: DOR in ALL as assessed by an Independent Review Committee

    DOR, defined as the time from achievement of CR or CRi to relapse or death due to any cause

    Measured: 24 months

  6. Phase 1: EFS in ALL as assessed by an Independent Review Committee

    EFS, defined as the date from rapcabtagene autoleucel infusion to the earliest date of relapse after CR/CRi, treatment failure (defined as failure to achieve CR/CRi within 12 weeks of infusion), or death due to any cause

    Measured: 24 months

  7. Phase 1: BOR in ALL as assessed by local Investigator

    BOR of CR/CRi

    Measured: 24 months

  8. Phase 1: DOR in ALL as assessed by local Investigator

    DOR, defined as the time from achievement of CR or CRi to relapse or death due to any cause.

    Measured: 24 months

  9. Phase 1: EFS in ALL as assessed by local Investigator

    EFS, defined as the date from rapcabtagene autoleucel infusion to the earliest date of relapse after CR/CRi, treatment failure (defined as failure to achieve CR/CRi within 12 weeks of infusion), or death due to any cause

    Measured: 24 months

  10. Phase 1: Overall survival in adult ALL

    OS defined as time from the date of infusion to the date of death due to any reason

    Measured: 24 months

  11. Phase 1: MRD negative status by flow cytometry in adult ALL

    Measured: 24 months

  12. Phase 1: Quality of life in adult ALL patients enrolled in the expansion part by use of Electronic Patient Reported Outcomes (ePRO) as per EORTC QLQ-C30 questionnaire

    Measured: 24 months

  13. Phase 1: Quality of life in adult ALL patients enrolled in the expansion part by use of Electronic Patient Reported Outcomes (ePRO) as per EQ-5D-3 questionnaire

    Measured: 24 months

  14. Phase 1/2: Cellular kinetics

    CAR transgene levels by quantitative polymerase chain reaction (qPCR) in peripheral blood, bone marrow and lymph nodes

    Measured: 24 months

  15. Phase 1/2: Immunogenicity

    Cellular and humoral responses to the CAR transgene

    Measured: 24 months

  16. Phase 2: Overall response rate (ORR)

    ORR defined as BOR of CR/PR as per Lugano criteria in 3L+ DLBCL and 1L HR LBCL

    Measured: 24 months

  17. Phase 2: Complete Response Rate (CRR)

    CRR at months 3, 6 in 3L+ DLBCL

    Measured: months 3, 6

  18. Phase 2: Complete Response Rate (CRR)

    CRR at months 6, 12 in 1L HR LBCL

    Measured: months 6, 12

  19. Phase 2: Duration of response (DOR)

    DOR defined as time from first CR/PR to first documented progression or death due to any cause in 3L+ DLBCL and 1L HR LBCL

    Measured: 24 months

  20. Phase 2: Progression-free survival (PFS)

    PFS defined as time from rapcabtagene autoleucel infusion to first documented progression or death due to any cause in 3L+ DLBCL and 1L HR LBCL

    Measured: 24 months

  21. Phase 2: Event-free survival (EFS)

    EFS defined as time from rapcabtagene autoleucel infusion to first documented progression, start of new anti-lymphoma therapy, biopsy-proven residual disease on or after month 6, or death due to any cause in 1L HR LBCL

    Measured: 24 months

  22. Phase 2: Overall survival (OS)

    OS defined as time from date of rapcabtagene autoleucel infusion to date of death due to any cause in 3L+ DLBCL and 1L HR LBCL

    Measured: 24 months

  23. Phase 2: Complete Response Rate (CRR) in subgroups 1) IPI 4-5 or DH/TH and 2) IPI 3 and not DH/TH

    CRR at months 6, 12 in 1L HR LBCL

    Measured: months 6, 12

  24. Phase 2: Overall response rate (ORR) in subgroups 1) IPI 4-5 or DH/TH and 2) IPI 3 and not DH/TH

    ORR defined as BOR of CR/PR as per Lugano criteria 1L HR LBCL

    Measured: 24 months

  25. Phase 2: Duration of response (DOR) in subgroups 1) IPI 4-5 or DH/TH and 2) IPI 3 and not DH/TH

    DOR defined as time from first CR/PR to first documented progression or death due to any cause in 1L HR LBCL

    Measured: 24 months

  26. Phase 2: Progression-free survival (PFS) in subgroups 1) IPI 4-5 or DH/TH and 2) IPI 3 and not DH/TH

    PFS defined as time from rapcabtagene autoleucel infusion to first documented progression or death due to any cause in 1L HR LBCL

    Measured: 24 months

  27. Phase 2: Event-free survival (EFS) in subgroups 1) IPI 4-5 or DH/TH and 2) IPI 3 and not DH/TH

    EFS defined as time from rapcabtagene autoleucel infusion to first documented progression, start of new anti-lymphoma therapy, biopsy-proven residual disease on or after month 6, or death due to any cause in 1L HR LBCL

    Measured: 24 months

  28. Phase 2: Overall survival (OS) in subgroups 1) IPI 4-5 or DH/TH and 2) IPI 3 and not DH/TH

    OS defined as time from date of rapcabtagene autoleucel infusion to date of death due to any cause in 1L HR LBCL

    Measured: 24 months

  29. Phase 2: Manufacturing vein to door time

    Time from apheresis completion until return of rapcabtagene autoleucel product to the clinic or hospital

    Measured: 24 months

Timeline

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

  1. First posted23 May 2019
  2. Study start26 Jun 2019
  3. Primary completion30 Jun 2027 (estimated)
  4. Study completion24 Jul 2027 (estimated)

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
218 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03960840
Sponsor's protocol ID
CYTB323A12101
Status last verified
Oct 2026
First submitted
21 May 2019
Last updated
29 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Rapcabtagene autoleucel single agent and Ibrutinib in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Novartis Pharmaceuticals at 37 sites in 8 countries.

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 13 inclusion and 9 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: under way, not looking for participants, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 37 sites in United States, Spain, France, Italy, Japan and 3 more countries. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

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?

Phase 1: Dose recommendation: Incidence and nature of Dose Limiting Toxicities (Dose Escalation part only) (time frame: 28 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 NCT03960840.

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 29 Oct 2026.

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