Recurrent Acute Lymphoblastic LeukemiaPhase 1NCT05418088
Genetically Engineered Cells (Anti-CD19/CD20/CD22 CAR T-cells) for the Treatment of Relapsed or Refractory Lymphoid Malignancies
A Phase 1 study testing Anti-CD19/CD20/CD22 CAR T-Cells, Cyclophosphamide and Fludarabine Phosphate in people with Recurrent Acute Lymphoblastic Leukemia and Recurrent B Acute Lymphoblastic Leukemia, run by Sumithira Vasu at 2 sites in United States.
Trial summary
This phase I trial tests the safety, side effects and best infusion dose of genetically engineered cells called anti-CD19/CD20/CD22 chimeric antigen receptor (CAR) T-cells following a short course of chemotherapy with cyclophosphamide and fludarabine in treating patients with lymphoid cancers (malignancies) that have… Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Recurrent Acute Lymphoblastic Leukemia, Recurrent B Acute Lymphoblastic Leukemia, Recurrent B-Cell Prolymphocytic Leukemia
- What is being tested?
- Anti-CD19/CD20/CD22 CAR T-Cells, Cyclophosphamide and Fludarabine Phosphate
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 2 sitesUnited States
- Study dates
- 30 Jun 2022to 1 Jul 2027
- 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 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Adult subjects with relapsed or refractory non-Hodgkin lymphoma with lesions =< 5 cm, indolent lymphomas, chronic lymphocytic leukemia without Richter's transformation, or B-prolymphocytic leukemia (Cohort A)
- OR adult subjects with lymphoid blast crisis, acute lymphoblastic leukemia, chronic lymphocytic leukemia with Richter's transformation, non-Hodgkin lymphoma with lesions > 5 cm and/or lymphoblastic lymphoma, or non-Hodgkin lymphoma with circulating lymphoma cells, B-Prolymphocytic leukemia with lesions > 5 cm (not including splenomegaly (Cohort B).
- OR Pediatric subjects with Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma
- Subjects must have been treated with at least two lines of therapy. Disease must have either progressed after the last regimen or presented failure to achieve complete remission with the last regimen. B-PLL is defined as having greater than 55% prolymphocytes in the peripheral blood
- Subjects with relapsed/refractory CLL after at least 2 prior lines of appropriate therapy and must have previously received an approved BTK inhibitor and venetoclax
- Subjects with refractory high-grade B-cell lymphoma who relapse within 12 months of autologous stem cell transplant
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- Subjects with relapsed/refractory B-prolymphocytic leukemia who received at least 1- 2 prior lines of appropriate therapy and who have failed or are ineligible for allogeneic stem cell transplant
- Subjects with relapsed/refractory acute B-lymphoblastic leukemia who received at least 2 prior lines of appropriate therapy or who have failed or are ineligible for allogeneic stem cell transplant.
- The patient's lymphoid malignancy must be positive for at least one target antigen (CD19 and/or CD20 and/or CD22), either by immunohistochemistry or flow cytometry analysis on the last biopsy available or peripheral blood for circulating disease.
- Patients who received blinatumomab or inotuzumab are eligible.
- Patients who received prior CAR T-cells are eligible, (commercial CD 19 CAR-T cells or dual CAR-T cells), if it has been at least 30 days since previous CAR T cell therapy and <5% of circulating levels of CD3+ cells express the prior CAR by flow cytometry.
- Age >= 2 years
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2. For patients < 16 years, Performance score Lansky >= 50
- Total bilirubin =< 1.5 times the institutional upper limit of normal for age
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 3 X institutional upper limit of normal for age
- Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 X institutional upper limit of normal for age
- Creatinine clearance more than or equal to 50 ml/min calculated by the Cockcroft - Gault formula, or by Schwartz formula for patients < 18 years
- Subjects must have adequate pulmonary function as defined as pulse oximetry >= 92% on room air
- Subjects must have adequate cardiac function as defined as left ventricular ejection fraction >= 40% in the most recent echocardiogram
- Absolute lymphocyte count > 100/uL
- Subjects (or legal guardians) must have the ability to understand and the willingness to sign a written informed consent document
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of < 1% per year during the treatment period and for at least 6 months after the Anti-CD19/20/22 CAR-T cell infusion
- A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (< 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptive s that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices
- The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm
- With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 6 months after the Anti-CD19/20/22 CAR-T cell infusion. Men must refrain from donating sperm during this same period
- With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 6 months after the human anti-CD19 CAR-T cell infusion to avoid potential embryonal or fetal exposure. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
Who cannot join
- Autologous transplant within 6 weeks of planned CAR-T cell infusion
- Allogeneic stem cell transplant or donor lymphocyte infusion within 2 months of planned CAR-T cell infusion and patients must be off immunosuppressive agents. Patients with live vaccines given 28 days prior to lymphodepletion (LD) chemotherapy will be excluded
- Active graft versus host disease
- Active central nervous system or meningeal involvement by lymphoma or leukemia. Subjects with untreated brain metastases/central nervous system (CNS) disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with a history of CNS or meningeal involvement must be in a documented remission by CSF evaluation and contrast-enhanced magnetic resonance imaging (MRI) imaging for at least 90 days prior to registration
- Active malignancy, other than non-melanoma skin cancer or carcinoma in situ (e.g.cervix, bladder, breast). Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial (e.g.
- Low Gleason score prostate Cancer)
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- A minimum of 28 days must have elapsed between prior treatment with investigational agent(s) and the day of lymphocyte collection
- Human immunodeficiency virus (HIV)-seropositive patients are allowable, however must be on effective anti-retroviral therapy with undetectable viral load within 6 months of enrollment to be eligible for this trial
- Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant or breastfeeding women are excluded from this study because CAR-T cell therapy may be associated with the potential for teratogenic or abortifacient effects. Women of childbearing potential must have a negative serum pregnancy test. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with CAR-T cells, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study
- Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy
- Patients with a positive hepatitis B core antibody or surface antigen are at high risk for hepatitis B virus (HBV) reaction and will require entecavir/tenofivir prophylaxis or serial hepatitis B (Hep B) PCR monitoring at the direction of an infectious disease specialist. Duration of prophylaxis to correspond with detection of Anti-CD19/20/22 CAR T cells/viral vector copies in serum or continued evidence of B-cell aplasia such as reduced intravenous immunoglobulin therapy (IVIG) levels. No antiviral prophylaxis is indicated with hepatitis C positivity with negative PCR
- Patients with history of clinically relevant CNS pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease
- History of autoimmune disease (i.e. rheumatoid arthritis, systemic lupus erythematosus) with requirement of immunosuppressive medication within 6 months
- Live vaccines given in 28 days prior to lymphodepleting chemotherapy
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
The Ohio State University Comprehensive Cancer Center contact
United States2 sites, 2 recruiting
- Recruiting
Nationwide Children's Hospital
Columbus, Ohio, 43203
Kennedy Thompson, 614-722-5043, Kennedy.thompson@nationwidechildrens.org
Lori Jewell, BA, 614-722-6576, Lori.Jewell@nationwidechildrens.org
- Recruiting
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Sumithira Vasu, MD, 614-293-8197, Sumithira.Vasu@osumc.edu
Sumithira Vasu, MD
About this study
Official title: Phase I Clinical Trial of Anti-CD19/20/22 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Lymphoid Malignancies (Non-Hodgkin Lymphoma, Acute Lymphoblastic Leukemia, Chronic Lymphocytic Leukemia, B-Prolymphocytic Leukemia)
This phase I trial tests the safety, side effects and best infusion dose of genetically engineered cells called anti-CD19/CD20/CD22 chimeric antigen receptor (CAR) T-cells following a short course of chemotherapy with cyclophosphamide and fludarabine in treating patients with lymphoid cancers (malignancies) that have come back (recurrent) or do not respond to treatment (refractory). Lymphoid malignancies eligible for this trial are: non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and B-prolymphocytic leukemia (B-PLL). T-cells (a type of white blood cell) form part of the body's immune system. CAR-T is a type of cell therapy that is used with gene-based therapies. CAR T-cells are made by taking a patient's own T-cells and genetically modifying them with a virus so that they are recognized by a group of proteins called CD19/CD20/CD22 which are found on the surface of cancer cells. Anti-CD19/CD20/CD22 CAR T-cells can recognize CD19/CD20/CD22, bind to the cancer cells and kill them. Giving combination chemotherapy helps prepare the body before CAR T-cell therapy. Giving CAR-T after cyclophosphamide and fludarabine may kill more tumor cells.
Read the detailed description
PRIMARY OBJECTIVE:
- To determine the safety of the treatment of relapsed/refractory non-Hodgkin lymphoma, relapsed/refractory chronic lymphocytic leukemia, refractory B-prolymphocytic leukemia and relapsed/refractory acute lymphoblastic leukemia with chimeric antigen receptor T cells targeting CD19/20/22 and to find the recommended phase II dose for this cellular therapy.
SECONDARY OBJECTIVES:
- To describe the safety profile of the infusion of CAR-T cells targeting CD19/20/22 in relapsed/refractory Non-Hodgkin lymphoma, relapsed/refractory chronic lymphocytic leukemia, refractory B-prolymphocytic leukemia and in relapsed/refractory acute lymphoblastic leukemia.
II. To describe the toxicities related to infusion of CAR-T cells targeting CD19/20/22.
III. To describe the overall response rate and complete response rate of relapsed B cell malignancies treated with CAR-T cells targeting CD19/20/22.
IV. To describe the overall and progression free survival of patients with relapsed lymphoma, CLL, B-PLL and ALL treated with anti-CD19/20/22 CAR-T cells.
EXPLORATORY OBJECTIVES:
- To describe the persistence of anti-CD19/20/22 CAR-T cells, measured by flow cytometry and quantitative polymerase chain reaction (qPCR).
II. To describe the T cell subpopulations of the anti-CD19/20/22 CAR-T cell product before infusion.
III. To describe the changes in anti-CD19/20/22 CAR-T cells after infusion and their correlation with disease response and adverse events.
IV. To investigate the correlation between changes in cytokine plasma concentrations and changes in anti-CD19/20/22 CAR-T cell subpopulations over time.
- To investigate proteomic changes in anti-CD19/20/22 CAR-T cell subpopulations over time.
VI.To investigate whether antigen escape occurs in patients treated with anti-CD19/20/22 CAR-T.
OUTLINE: This is a phase I dose-escalation study of anti-CD19/CD20/CD22 CAR-T cells. Patients with NHL with lesions =< 5 cm, indolent lymphomas, CLL (without Richter's transformation), or B-PLL are assigned to Cohort A. Patients with ALL, CLL (with Richter's transformation), NHL with lesions > 5 cm and/or lymphoblastic lymphoma, or NHL with circulating lymphoma cells are assigned to Cohort B.
COHORT A:
LYMPHODEPLETIVE REGIMEN: Patients receive cyclophosphamide intravenously (IV) over 60 minutes on day -6 and fludarabine IV over 30 minutes on days -5 to -3 in the absence of disease progression or unacceptable toxicity.
CAR T-CELL THERAPY: Patients receive anti-CD19/CD20/CD22 CAR-T cells IV over 5-30 minutes on day 0.
Patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) and may undergo tissue biopsy during screening, undergo apheresis on study, and undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.
COHOHRT B:
LYMPHODEPLETIVE REGIMEN: Patients receive cyclophosphamide IV over 60 minutes on day -6 and fludarabine IV over 30 minutes on days -5 to -3 in the absence of disease progression or unacceptable toxicity.
CAR T-CELL THERAPY: Patients receive anti-CD19/CD20/CD22 CAR-T cells IV over 5-30 minutes on day 0 and 7.
Patients undergo ECHO or MUGA and may undergo tissue biopsy during screening, undergo apheresis on study, and undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.
COHORT C:
LYMPHODEPLETIVE REGIMEN: Patients receive cyclophosphamide IV on days -6 and -5 and fludarabine IV on days -6 to -3 in the absence of disease progression or unacceptable toxicity.
CAR T-CELL THERAPY: Patients receive anti-CD19/CD20/CD22 CAR-T cells IV over 5-30 minutes on day 0 and 7.
Patients undergo ECHO or MUGA and may undergo tissue biopsy during screening, undergo apheresis on study, and undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.
After completion of study treatment, patients in Cohort A are followed up on days 1-7, 14, 21, 30, 60, 90, at months 6, 24, 36, 48, and 60, and then annually for 6-15 years. Patients in Cohort B and Cohort C are followed up on days 9, 14, 21, 30, 60, 90, at months 6, 24, 36, 48, and 60, and then annually for 6-15 years.
- Conditions
- Recurrent Acute Lymphoblastic Leukemia, Recurrent B Acute Lymphoblastic Leukemia, Recurrent B-Cell Prolymphocytic Leukemia, Recurrent Chronic Lymphocytic Leukemia, Recurrent High Grade B-Cell Lymphoma, Recurrent Indolent Non-Hodgkin Lymphoma
- Being tested
- Anti-CD19/CD20/CD22 CAR T-Cells, Cyclophosphamide, Fludarabine Phosphate, Echocardiography, Multigated Acquisition Scan
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Burkitt Lymphoma, Leukemia, Prolymphocytic, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-CD19/CD20/CD22 CAR T-CellsBiological
Also called Anti-CD19/20/22 Chimeric Antigen Receptor T-Cells, CD19/CD20/CD22-targeted CAR-T Cells
Given IV
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida
Given IV
Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara
Given IV
EchocardiographyProcedure or surgery
Also called EC
Undergo echocardiography
Multigated Acquisition ScanProcedure or surgery
Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan
Undergo MUGA scan
BiopsyProcedure or surgery
Also called BIOPSY_TYPE, Bx
Undergo tissue biopsy
PheresisProcedure or surgery
Also called Apheresed, apheresis, Blood Component Removal, Collection
Undergo apheresis
Bone Marrow Aspiration and BiopsyProcedure or surgery
Undergo bone marrow aspiration and biopsy
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo blood sample collection
| Study group | Role | What they receive |
|---|---|---|
| Cohort A (lymphodepletion; anti-CD19/CD20/CD22 CAR-T cells) | Experimental | LYMPHODEPLETIVE REGIMEN: Patients receive cyclophosphamide IV over 60 minutes on day -6 and fludarabine IV over 30 minutes on days -5 to -3 in the absence of disease progression or unacceptable toxicity.
CAR T-CELL THERAPY: Patients receive anti-CD19/CD20/CD22 CAR-T cells IV over 5-30 minutes on day 0.
Patients undergo ECHO or MUGA and may undergo tissue biopsy during screening, undergo apheresis on study, and undergo bone marrow biopsy and aspiration and blood sample collection throughout the study. Receives: Biological: Anti-CD19/CD20/CD22 CAR T-Cells; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Procedure: Echocardiography; Procedure: Multigated Acquisition Scan; Procedure: Biopsy; Procedure: Pheresis; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Biospecimen Collection |
| Cohort B (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells) | Experimental | LYMPHODEPLETIVE REGIMEN: Patients receive cyclophosphamide IV over 60 minutes on day -6 and fludarabine IV over 30 minutes on days -5 to -3 in the absence of disease progression or unacceptable toxicity.
CAR T-CELL THERAPY: Patients receive anti-CD19/CD20/CD22 CAR-T cells IV over 5-30 minutes on day 0 and 7.
Patients undergo ECHO or MUGA and may undergo tissue biopsy during screening, undergo apheresis on study, and undergo bone marrow biopsy and aspiration and blood sample collection throughout the study. Receives: Biological: Anti-CD19/CD20/CD22 CAR T-Cells; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Procedure: Echocardiography; Procedure: Multigated Acquisition Scan; Procedure: Biopsy; Procedure: Pheresis; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Biospecimen Collection |
| Cohort C (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells) | Experimental | LYMPHODEPLETIVE REGIMEN: Patients receive cyclophosphamide IV on days -6 and -5 and fludarabine IV on days -6 to -3 in the absence of disease progression or unacceptable toxicity.
CAR T-CELL THERAPY: Patients receive anti-CD19/CD20/CD22 CAR-T cells IV over 5-30 minutes on day 0 and 7.
Patients undergo ECHO or MUGA and may undergo tissue biopsy during screening, undergo apheresis on study, and undergo bone marrow biopsy and aspiration and blood sample collection throughout the study. Receives: Biological: Anti-CD19/CD20/CD22 CAR T-Cells; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Procedure: Echocardiography; Procedure: Multigated Acquisition Scan; Procedure: Biopsy; Procedure: Pheresis; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Biospecimen Collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended phase II dose of anti-CD19/CD20/CD22 CAR-T cells for each study group (Cohort A, Cohort B, and Cohort C)
Measured: Up to 30 days after CAR T-cell infusion
Secondary outcomes (5)
Incidence of adverse events
Will be evaluated with descriptive statistics for the frequencies of adverse events of different grades.
Measured: Up to 12 months after completion of study treatment
Overall response rate
Will be evaluated with descriptive statistics with proportions used to describe response rates.
Measured: Up to 15 years
Complete response rate
Will be evaluated with descriptive statistics with proportions used to describe response rates.
Measured: Up to 15 years
Overall survival
Will be calculated using Kaplan Meier method, comparisons between groups will be done using the log rank test.
Measured: Up to 15 years
Progression-free survival
Will be calculated using Kaplan Meier method, comparisons between groups will be done using the log rank test.
Measured: From entry onto study until lymphoma progression or death from any cause, assessed up to 15 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2022
- Study start30 Jun 2022
- Primary completion1 Jul 2027 (estimated)
- Study completion1 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sumithira Vasu
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, Sumithira Vasu, Ohio State University Comprehensive Cancer Center
- Investigators
- Sumithira Vasu, MD, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05418088
- Sponsor's protocol ID
- OSU-21170
- Other IDs
- NCI-2022-02972, R01CA276374
- Status last verified
- May 2026
- First submitted
- 16 May 2022
- Last updated
- 29 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Clinical Trial of Anti-CD19/20/22 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Lymphoid Malignancies (Non-Hodgkin Lymphoma, Acute Lymphoblastic Leukemia, Chronic Lymphocytic Leukemia, B-Prolymphocytic Leukemia)
- ClinicalTrials.gov ID
- NCT05418088
- Acronym / sponsor ID
- OSU-21170
- Conditions
- Recurrent Acute Lymphoblastic Leukemia, Recurrent B Acute Lymphoblastic Leukemia, Recurrent B-Cell Prolymphocytic Leukemia, Recurrent Chronic Lymphocytic Leukemia, Recurrent High Grade B-Cell Lymphoma, Recurrent Indolent Non-Hodgkin Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- Sumithira VasuUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 30 Jun 2022 (actual)
- Primary completion
- 1 Jul 2027 (estimated)
- Study completion
- 1 Jul 2027 (estimated)
- First posted
- 14 Jun 2022 (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 phase I trial tests the safety, side effects and best infusion dose of genetically engineered cells called anti-CD19/CD20/CD22 chimeric antigen receptor (CAR) T-cells following a short course of chemotherapy with cyclophosphamide and fludarabine in treating patients with lymphoid cancers (malignancies) that have come back (recurrent) or do not respond to treatment (refractory). Lymphoid malignancies eligible for this trial are: non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and B-prolymphocytic leukemia (B-PLL). T-cells (a type of white blood cell) form part of the body's immune system. CAR-T is a type of cell therapy that is used with gene-based therapies. CAR T-cells are made by taking a patient's own T-cells and genetically modifying them with a virus so that they are recognized by a group of proteins called CD19/CD20/CD22 which are found on the surface of cancer cells. Anti-CD19/CD20/CD22 CAR T-cells can recognize CD19/CD20/CD22, bind to the cancer cells and kill them. Giving combination chemotherapy helps prepare the body before CAR T-cell therapy. Giving CAR-T after cyclophosphamide and fludarabine may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVE:
- To determine the safety of the treatment of relapsed/refractory non-Hodgkin lymphoma, relapsed/refractory chronic lymphocytic leukemia, refractory B-prolymphocytic leukemia and relapsed/refractory acute lymphoblastic leukemia with chimeric antigen receptor T cells targeting CD19/20/22 and to find the recommended phase II dose for this cellular therapy.
SECONDARY OBJECTIVES:
- To describe the safety profile of the infusion of CAR-T cells targeting CD19/20/22 in relapsed/refractory Non-Hodgkin lymphoma, relapsed/refractory chronic lymphocytic leukemia, refractory B-prolymphocytic leukemia and in relapsed/refractory acute lymphoblastic leukemia.
II. To describe the toxicities related to infusion of CAR-T cells targeting CD19/20/22.
III. To describe the overall response rate and complete response rate of relapsed B cell malignancies treated with CAR-T cells targeting CD19/20/22.
IV. To describe the overall and progression free survival of patients with relapsed lymphoma, CLL, B-PLL and ALL treated with anti-CD19/20/22 CAR-T cells.
EXPLORATORY OBJECTIVES:
- To describe the persistence of anti-CD19/20/22 CAR-T cells, measured by flow cytometry and quantitative polymerase chain reaction (qPCR).
II. To describe the T cell subpopulations of the anti-CD19/20/22 CAR-T cell product before infusion.
III. To describe the changes in anti-CD19/20/22 CAR-T cells after infusion and their correlation with disease response and adverse events.
IV. To investigate the correlation between changes in cytokine plasma concentrations and changes in anti-CD19/20/22 CAR-T cell subpopulations over time.
- To investigate proteomic changes in anti-CD19/20/22 CAR-T cell subpopulations over time.
VI.To investigate whether antigen escape occurs in patients treated with anti-CD19/20/22 CAR-T.
OUTLINE: This is a phase I dose-escalation study of anti-CD19/CD20/CD22 CAR-T cells. Patients with NHL with lesions =< 5 cm, indolent lymphomas, CLL (without Richter's transformation), or B-PLL are assigned to Cohort A. Patients with ALL, CLL (with Richter's transformation), NHL with lesions > 5 cm and/or lymphoblastic lymphoma, or NHL with circulating lymphoma cells are assigned to Cohort B.
COHORT A:
LYMPHODEPLETIVE REGIMEN: Patients receive cyclophosphamide intravenously (IV) over 60 minutes on day -6 and fludarabine IV over 30 minutes on days -5 to -3 in the absence of disease progression or unacceptable toxicity.
CAR T-CELL THERAPY: Patients receive anti-CD19/CD20/CD22 CAR-T cells IV over 5-30 minutes on day 0.
Patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) and may undergo tissue biopsy during screening, undergo apheresis on study, and undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.
COHOHRT B:
LYMPHODEPLETIVE REGIMEN: Patients receive cyclophosphamide IV over 60 minutes on day -6 and fludarabine IV over 30 minutes on days -5 to -3 in the absence of disease progression or unacceptable toxicity.
CAR T-CELL THERAPY: Patients receive anti-CD19/CD20/CD22 CAR-T cells IV over 5-30 minutes on day 0 and 7.
Patients undergo ECHO or MUGA and may undergo tissue biopsy during screening, undergo apheresis on study, and undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.
COHORT C:
LYMPHODEPLETIVE REGIMEN: Patients receive cyclophosphamide IV on days -6 and -5 and fludarabine IV on days -6 to -3 in the absence of disease progression or unacceptable toxicity.
CAR T-CELL THERAPY: Patients receive anti-CD19/CD20/CD22 CAR-T cells IV over 5-30 minutes on day 0 and 7.
Patients undergo ECHO or MUGA and may undergo tissue biopsy during screening, undergo apheresis on study, and undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.
After completion of study treatment, patients in Cohort A are followed up on days 1-7, 14, 21, 30, 60, 90, at months 6, 24, 36, 48, and 60, and then annually for 6-15 years. Patients in Cohort B and Cohort C are followed up on days 9, 14, 21, 30, 60, 90, at months 6, 24, 36, 48, and 60, and then annually for 6-15 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort A (lymphodepletion; anti-CD19/CD20/CD22 CAR-T cells) | Experimental | Biological: Anti-CD19/CD20/CD22 CAR T-Cells, Drug: Cyclophosphamide, Drug: Fludarabine Phosphate, Procedure: Echocardiography, Procedure: Multigated Acquisition Scan, Procedure: Biopsy, Procedure: Pheresis, Procedure: Bone Marrow Aspiration and Biopsy, Procedure: Biospecimen CollectionLYMPHODEPLETIVE REGIMEN: Patients receive cyclophosphamide IV over 60 minutes on day -6 and fludarabine IV over 30 minutes on days -5 to -3 in the absence of disease progression or unacceptable toxicity. CAR T-CELL THERAPY: Patients receive anti-CD19/CD20/CD22 CAR-T cells IV over 5-30 minutes on day 0. Patients undergo ECHO or MUGA and may undergo tissue biopsy during screening, undergo apheresis on study, and undergo bone marrow biopsy and aspiration and blood sample collection throughout the study. |
| Cohort B (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells) | Experimental | Biological: Anti-CD19/CD20/CD22 CAR T-Cells, Drug: Cyclophosphamide, Drug: Fludarabine Phosphate, Procedure: Echocardiography, Procedure: Multigated Acquisition Scan, Procedure: Biopsy, Procedure: Pheresis, Procedure: Bone Marrow Aspiration and Biopsy, Procedure: Biospecimen CollectionLYMPHODEPLETIVE REGIMEN: Patients receive cyclophosphamide IV over 60 minutes on day -6 and fludarabine IV over 30 minutes on days -5 to -3 in the absence of disease progression or unacceptable toxicity. CAR T-CELL THERAPY: Patients receive anti-CD19/CD20/CD22 CAR-T cells IV over 5-30 minutes on day 0 and 7. Patients undergo ECHO or MUGA and may undergo tissue biopsy during screening, undergo apheresis on study, and undergo bone marrow biopsy and aspiration and blood sample collection throughout the study. |
| Cohort C (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells) | Experimental | Biological: Anti-CD19/CD20/CD22 CAR T-Cells, Drug: Cyclophosphamide, Drug: Fludarabine Phosphate, Procedure: Echocardiography, Procedure: Multigated Acquisition Scan, Procedure: Biopsy, Procedure: Pheresis, Procedure: Bone Marrow Aspiration and Biopsy, Procedure: Biospecimen CollectionLYMPHODEPLETIVE REGIMEN: Patients receive cyclophosphamide IV on days -6 and -5 and fludarabine IV on days -6 to -3 in the absence of disease progression or unacceptable toxicity. CAR T-CELL THERAPY: Patients receive anti-CD19/CD20/CD22 CAR-T cells IV over 5-30 minutes on day 0 and 7. Patients undergo ECHO or MUGA and may undergo tissue biopsy during screening, undergo apheresis on study, and undergo bone marrow biopsy and aspiration and blood sample collection throughout the study. |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (27 listed)
- Adult subjects with relapsed or refractory non-Hodgkin lymphoma with lesions =< 5 cm, indolent lymphomas, chronic lymphocytic leukemia without Richter's transformation, or B-prolymphocytic leukemia (Cohort A)
- OR adult subjects with lymphoid blast crisis, acute lymphoblastic leukemia, chronic lymphocytic leukemia with Richter's transformation, non-Hodgkin lymphoma with lesions > 5 cm and/or lymphoblastic lymphoma, or non-Hodgkin lymphoma with circulating lymphoma cells, B-Prolymphocytic leukemia with lesions > 5 cm (not including splenomegaly (Cohort B).
- OR Pediatric subjects with Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma
- Subjects must have been treated with at least two lines of therapy. Disease must have either progressed after the last regimen or presented failure to achieve complete remission with the last regimen. B-PLL is defined as having greater than 55% prolymphocytes in the peripheral blood
- Subjects with relapsed/refractory CLL after at least 2 prior lines of appropriate therapy and must have previously received an approved BTK inhibitor and venetoclax
Key exclusion criteria (15 listed)
- Autologous transplant within 6 weeks of planned CAR-T cell infusion
- Allogeneic stem cell transplant or donor lymphocyte infusion within 2 months of planned CAR-T cell infusion and patients must be off immunosuppressive agents. Patients with live vaccines given 28 days prior to lymphodepletion (LD) chemotherapy will be excluded
- Active graft versus host disease
- Active central nervous system or meningeal involvement by lymphoma or leukemia. Subjects with untreated brain metastases/central nervous system (CNS) disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with a history of CNS or meningeal involvement must be in a documented remission by CSF evaluation and contrast-enhanced magnetic resonance imaging (MRI) imaging for at least 90 days prior to registration
- Active malignancy, other than non-melanoma skin cancer or carcinoma in situ (e.g.cervix, bladder, breast). Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial (e.g.
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 |
|---|---|---|
| Anti-CD19/CD20/CD22 CAR T-CellsAlso: Anti-CD19/20/22 Chimeric Antigen Receptor T-Cells, CD19/CD20/CD22-targeted CAR-T CellsGiven IV | Biological | Cohort A (lymphodepletion; anti-CD19/CD20/CD22 CAR-T cells), Cohort B (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells), Cohort C (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells) |
| CyclophosphamideAlso: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, CiclofosfamidaGiven IV | Drug | Cohort A (lymphodepletion; anti-CD19/CD20/CD22 CAR-T cells), Cohort B (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells), Cohort C (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells) |
| Fludarabine PhosphateAlso: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, FludaraGiven IV | Drug | Cohort A (lymphodepletion; anti-CD19/CD20/CD22 CAR-T cells), Cohort B (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells), Cohort C (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells) |
| EchocardiographyAlso: ECUndergo echocardiography | Procedure or surgery | Cohort A (lymphodepletion; anti-CD19/CD20/CD22 CAR-T cells), Cohort B (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells), Cohort C (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells) |
| Multigated Acquisition ScanAlso: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool ScanUndergo MUGA scan | Procedure or surgery | Cohort A (lymphodepletion; anti-CD19/CD20/CD22 CAR-T cells), Cohort B (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells), Cohort C (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells) |
| BiopsyAlso: BIOPSY_TYPE, BxUndergo tissue biopsy | Procedure or surgery | Cohort A (lymphodepletion; anti-CD19/CD20/CD22 CAR-T cells), Cohort B (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells), Cohort C (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells) |
| PheresisAlso: Apheresed, apheresis, Blood Component Removal, CollectionUndergo apheresis | Procedure or surgery | Cohort A (lymphodepletion; anti-CD19/CD20/CD22 CAR-T cells), Cohort B (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells), Cohort C (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells) |
| Bone Marrow Aspiration and BiopsyUndergo bone marrow aspiration and biopsy | Procedure or surgery | Cohort A (lymphodepletion; anti-CD19/CD20/CD22 CAR-T cells), Cohort B (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells), Cohort C (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells) |
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Specimen CollectionUndergo blood sample collection | Procedure or surgery | Cohort A (lymphodepletion; anti-CD19/CD20/CD22 CAR-T cells), Cohort B (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells), Cohort C (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells) |
Primary outcome
Recommended phase II dose of anti-CD19/CD20/CD22 CAR-T cells for each study group (Cohort A, Cohort B, and Cohort C)
Time frame: Up to 30 days after CAR T-cell infusion
5 secondary outcomes
Incidence of adverse events
Time frame: Up to 12 months after completion of study treatment
Overall response rate
Time frame: Up to 15 years
Complete response rate
Time frame: Up to 15 years
Overall survival
Time frame: Up to 15 years
Progression-free survival
Time frame: From entry onto study until lymphoma progression or death from any cause, assessed up to 15 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 29 May 2026.
- The JameslineLink provided by the sponsor.
- 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.
The Ohio State University Comprehensive Cancer Center contact
Sumithira Vasu, MD principal investigator
Ohio State University Comprehensive Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Anti-CD19/CD20/CD22 CAR T-Cells, Cyclophosphamide and Fludarabine Phosphate in people with Recurrent Acute Lymphoblastic Leukemia and Recurrent B Acute Lymphoblastic Leukemia, run by Sumithira Vasu 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 27 inclusion and 15 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 29 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 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 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?
Contact The Ohio State University Comprehensive Cancer Center (800-293-5066, OSUCCCClinicaltrials@osumc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recommended phase II dose of anti-CD19/CD20/CD22 CAR-T cells for each study group (Cohort A, Cohort B, and Cohort C) (time frame: Up to 30 days after CAR T-cell infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 May 2026.