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Recurrent Transformed Chronic Lymphocytic LeukemiaPhase 2NCT05672173

Lisocabtagene Maraleucel, Nivolumab and Ibrutinib for the Treatment of Richter's Transformation

A Phase 2 study testing Biopsy, Biospecimen Collection and Bone Marrow Biopsy in people with Recurrent Transformed Chronic Lymphocytic Leukemia and Refractory Transformed Chronic Lymphocytic Leukemia, run by City of Hope Medical Center at 2 sites in United States.

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 phase II trial tests how well adding lisocabtagene maraleucel (liso-cel) to nivolumab and ibrutinib works in treating patients with Richter's transformation. Liso-cel is in a class of medications called autologous cellular immunotherapy, a type of medication prepared by using cells from patient's own blood. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biopsy, Biospecimen Collection and Bone Marrow Biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
2 sitesUnited States
Study dates
2 Jun 2023to 24 Aug 2027
Phase
Phase 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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Documented informed consent of the participant
  • Agreement for confirmatory pre-treatment tumor biopsy
  • If a patient does not have an easily accessible lymph node to biopsy without excessive risk in the opinion of the investigator, archival biopsy material reviewed by a hematopathologist at the enrolling site for study eligibility and baseline correlatives may be acceptable with approval from the Study principal investigator (PI)
  • Age: >= 18 years
  • Eastern cooperative oncology group (ECOG) <= 2
  • Histologically confirmed Richter's Transformation (RT)
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  • Relapsed / refractory following >=2 prior lines of systemic therapy; OR refractory to first-line chemoimmunotherapy; OR relapsed within 12 months of first line chemoimmunotherapy; OR relapsed after first line of chemoimmunotherapy and not eligible for hematopoietic stem cell transplantation due to comorbidities or age
  • Eligible to receive liso-cel and ibrutinib per package inserts
  • Fully recovered from the acute toxic effects (except alopecia) to <= Grade 1 to prior anti-cancer therapy
  • Absolute neutrophil count (ANC) >= 750/mm^3 unless there is bone marrow involvement
  • Platelets >= 75,000/mm^3 unless there is bone marrow involvement
  • Total bilirubin =< 1.5 X ULN (unless has Gilbert's disease)
  • Aspartate aminotransferase (AST) =< 2.5 x ULN
  • Alanine aminotransferase (ALT) =< 2.5 x ULN
  • Creatinine clearance of >= 30 mL/min per 24 hour urine test or the Cockcroft-Gault formula
  • International Normalized Ratio (INR) OR Prothrombin (PT) =< 1.5 x ULN
  • Activated Partial Thromboplastin Time (aPTT) =< 1.5 x ULN
  • Left ventricular ejection fraction (LVEF) >= 40%
  • Note: To be performed within 28 days prior to Day 1 of protocol therapy.
  • Seronegative for HCV*, active HBV (Surface Antigen Negative), and syphilis (RPR)
  • If positive, Hepatitis C RNA quantitation must be performed OR
  • If seropositive for HCV or HBV, nucleic acid quantitation must be performed. Viral load must be undetectable
  • Meets other institutional and federal requirements for infectious disease titer requirements
  • Note: Infectious disease testing to be performed within 28 days prior to Day 1 of protocol therapy
  • Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
  • If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Agreement by females and males of childbearing potential* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 5 months after the last dose of protocol therapy
  • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

Who cannot join

  • Subjects who previously received PD1 or PD-L1 inhibitor therapy
  • Autologous stem cell transplant within 3 months prior to Day 1 of protocol therapy
  • Allogeneic stem cell transplant within 3 months prior to Day 1 of protocol therapy and no active graft versus host disease (GVHD) or need for immunosuppressants
  • Chemotherapy, radiation therapy, immunotherapy within 14 days prior to Day 1 of protocol therapy
  • Strong CYP3A inducers within 14 days prior to Day 1 of protocol therapy
  • Warfarin within 5 days prior to Day 1 of protocol therapy
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  • Current requirement for oxygen supplementation
  • Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. Physiologic replacement of steroids (prednisone =< 7.5 mg /day or equivalent) is allowed throughout the study. Use of "bridging" steroids, to control disease, after leukapheresis and until 3 days prior to CAR T cell infusion, is allowed
  • Subjects with lymphoma only involving the central nervous system
  • Class III/IV cardiovascular disability according to the New York Heart Association (NYHA) Classification
  • Subjects with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of screening
  • Subjects with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, including seizure disorder
  • Subjects with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
  • Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
  • History of stroke or intracranial hemorrhage within 6 months prior to screening
  • History of other malignancies, except for malignancy surgically resected (or treated with other modalities) with curative intent, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; non-muscle invasive bladder cancer; malignancy treated with curative intent with no known active disease present for >= 3 years
  • Clinically significant uncontrolled illness
  • Active infection requiring antibiotics
  • Known history of immunodeficiency virus (HIV)
  • Females only: Pregnant or breastfeeding
  • Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis) not requiring systemic treatment, well controlled asthma and/or mild allergic rhinitis (seasonal allergies) are eligible
  • Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • City of Hope Medical Center

    Duarte, California, 91010

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: Phase 2 Study of the Combination of Lisocabtagene Maraleucel, Nivolumab, and Ibrutinib in Richter's Transformation

This phase II trial tests how well adding lisocabtagene maraleucel (liso-cel) to nivolumab and ibrutinib works in treating patients with Richter's transformation. Liso-cel is in a class of medications called autologous cellular immunotherapy, a type of medication prepared by using cells from patient's own blood. It works by causing the body's immune system (a group of cells, tissues, and organs that protects the body from attack by bacteria, viruses, cancer cells and other substances that cause disease) to fight the cancer cells. Nivolumab is in a class of medications called monoclonal antibodies. It works by helping the immune system to slow or stop the grown of cancer. Ibrutinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop the spread of cancer cells. Giving ibrutinib and nivolumab with Liso-cel may kill more cancer cells in patients with Richter's transformation.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Evaluate the complete response (CR) rate after cycle 3 following lisocabtagene maraleucel (liso-cel) in combination with nivolumab and ibrutinib to treat patients with Richter's transformation (RT).

II. Assess the Unacceptable toxicities (UT) rate within the first 28 days during cycle 1 following liso-cel infusion. (Safety lead-in only)

SECONDARY OBJECTIVES:

  1. Assess the safety of liso-cel, nivolumab and ibrutinib to treat patients with RT.

II. Estimate the best CR rate. III. Estimate the best overall response rate (ORR). IV. Estimate duration of response (DOR) at 2 years. V. Assess minimal residual disease (MRD) post liso-cel in participants with CLL at baseline.

VI. Estimate progression free survival (PFS) at 2 years. VII. Estimate overall survival (OS) at 2 years.

EXPLORATORY OBJECTIVES:

  1. Evaluate predictive biomarkers of response (genetic and immune) in peripheral blood, apheresis product, infusion product and circulating tumor (ct)DNA.

II. Evaluate the ability of MRD assessed by ctDNA analysis to predict PFS. III. Evaluate changes in the lymph node microenvironment during nivolumab therapy, with an optional pre-CAR T cell infusion lymph node biopsy.

IV. Evaluate the effect of liso-cel on CD19 expression on tumor cells at disease progression.

OUTLINE:

Patients receive ibrutinib orally (PO), nivolumab intravenously (IV), fludarabine IV, cyclophosphamide IV, and liso-cel IV on study. Patients also undergo apheresis, positron emission tomography (PET)/computed tomography (CT), collection of blood samples, and bone marrow biopsy on study. Patients may receive low-moderate intensity chemotherapy in combination with the study induction therapy per treating physician discretion with approval of study principal investigator.

Being tested
Biopsy, Biospecimen Collection, Bone Marrow Biopsy, Computed Tomography, Cyclophosphamide

What participants receive

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

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo tumor biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood specimen collection

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy and/or aspiration

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo PET/CT

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • IbrutinibDrug

    Also called BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

    Given PO

  • Lisocabtagene MaraleucelBiological

    Also called Anti-CD19-CAR Genetically Engineered Autologous T Lymphocytes JCAR017, Anti-CD19-CAR Genetically Engineered Autologous T-lymphocytes JCAR017, Autologous Anti-CD19-EGFRt-4-1BB-zeta-modified CAR CD8+ and CD4+ T-lymphocytes JCAR017, Breyanzi

    Given IV

  • NivolumabBiological

    Also called BMS-936558, CMAB819, MDX-1106, NIVO

    Given IV

  • PheresisProcedure or surgery

    Also called Apheresed, Apheresis, Blood Component Removal, Collection, Apheresis/Leukapheresis

    Undergo apheresis

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan

    Undergo PET/CT

Study groups in NCT05672173
Study groupRoleWhat they receive
Treatment (nivolumab, ibrutinib, chemotherapy, liso-cel)ExperimentalPatients receive ibrutinib PO, nivolumab IV, fludarabine IV, cyclophosphamide IV, and liso-cel IV on study. Patients also undergo apheresis, PET/CT, biospecimen collection, and bone marrow biopsy on study. Patients may receive low-moderate intensity chemotherapy in combination with the study induction therapy per treating physician discretion with approval of study principal investigator.
Receives: Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Ibrutinib; Biological: Lisocabtagene Maraleucel; Biological: Nivolumab; Procedure: Pheresis; Procedure: Positron Emission Tomography

What is being measured

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

  1. Complete Response (CR)

    After cycle 3, the rate and associated 95% binomial exact confidence interval will be estimated.

    Measured: Up to 2 years

  2. Unacceptable Toxicity (UT)

    Toxicities will be summarized by organ, severity, time of onset and characteristic. UT will be described individually and summarized by count and rate/percentage.

    Measured: Up to 28 days post CAR T cell infusion

Secondary outcomes (7)

  1. Toxicity

    Toxicities will be summarized by organ, severity, time of onset and characteristic. Assessed per ASTCT Consensus Criteria

    Measured: Up to 2 years

  2. Best Complete Response (CR)

    Defined as the proportion of patients that achieve CR at any time from start of protocol treatment to any disease progression or start of new anticancer treatment.

    Measured: Up to 2 years

  3. Overall Response Rate (ORR)

    Defined as the proportion of patients that achieve a best response of CR or partial response (PR) from start of protocol treatment prior to any disease progression or start of new anticancer treatment.

    Measured: Up to 2 years

  4. Duration of Response (DOR)

    Defined as the time from the first documented CR or PR through disease relapse, progression or death. Data for those patients without CR/ PR, disease progression, relapse or death will be captured at last follow up or start of non-protocol anticancer therapy. Those patients that do not achieve CR/PR will be excluded. Kaplan-Meier product limit method with log-log transformation for the confidence interval will be used to estimate the DOR.

    Measured: Up to 2 years

  5. Minimal Residual Disease (MRD)

    Evaluated in the peripheral blood and bone marrow using ClonoSEQ analysis. MRD at baseline will be summarized by descriptive analysis.

    Measured: Up to 2 years

  6. Progression Free Survival (PFS)

    Data for patients without disease relapse/ progression or death will be collected at the last follow-up or at start of non-protocol anticancer therapy. Kaplan-Meier product limit method with log-log transformation for the confidence interval will be used to estimate the PFS.

    Measured: From start of protocol treatment through disease relapse/ progression or death, assessed up to 2 years

  7. Overall Survival (OS)

    Data for alive patients will be collected at last follow up. Kaplan-Meier product limit method with log-log transformation for the confidence interval will be used to estimate the OS.

    Measured: From the start of protocol treatment through death due to any cause, assessed up to 2 years

Timeline

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

  1. First posted5 Jan 2023
  2. Study start2 Jun 2023
  3. Primary completion24 Aug 2027 (estimated)
  4. Study completion24 Aug 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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05672173
Sponsor's protocol ID
22040
Other IDs
NCI-2022-10247, 22040, P30CA033572
Status last verified
Sep 2026
First submitted
3 Jan 2023
Last updated
1 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biopsy, Biospecimen Collection and Bone Marrow Biopsy in people with Recurrent Transformed Chronic Lymphocytic Leukemia and Refractory Transformed Chronic Lymphocytic Leukemia, run by City of Hope Medical Center at 2 sites 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 28 inclusion and 23 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 1 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 2 sites 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 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?

Complete Response (CR) (time frame: Up to 2 years). The study lists 2 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 NCT05672173.

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 1 Oct 2026.

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