Metabolically Fit CD19 CAR T-cell Therapy With CD34 Selection in Patients With CD19+ Relapsed/Refractory NHL, CLL/SLL
A Phase 1b Dose Escalation Study of Metabolically Fit CD19 Chimeric Antigen Receptor (CAR) T Cells With CD34 Selection Markers in Adult Patients With Relapsed or Refractory CD19 B-Cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years and older
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
Not stated in the study description — ask the study team about visits and procedures.
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study tests different doses of a CAR T-cell treatment, which uses changed immune cells to fight cancer. It is for adults with certain lymphomas or CLL/SLL whose cancer has come back or has not responded to treatment. The cancer must have a marker called CD19.
This is a single-center, nonrandomized, open-label dose-escalation study followed by dose-expansion of CD19- CD34t metabolically programmed CAR T-cell therapy in adult patients with relapsed or refractory CD19 B-cell non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Be age 18 or older and have a confirmed type of lymphoma or CLL/SLL allowed in the study.
- Have cancer that returned, did not respond, or worsened after earlier treatment, or could not tolerate treatment for CLL/SLL. The number and type of past treatments needed depend on the cancer type.
- Be able to care for yourself and be up and about at least half of the day. Have enough caregiver support for CAR T-cell treatment.
- Have cancer measuring at least 1.5 cm on a scan. For CLL without cancer measurable on scans, a bone marrow sample must show more than 5% CLL.
- Meet blood count, liver, kidney, heart, and oxygen level requirements. Some blood count and liver test exceptions are allowed.
- If you had treatment aimed at CD19 before, a tissue sample taken afterward must show enough CD19.
- If you have hepatitis B, hepatitis C, or HIV, meet the study’s treatment and virus test rules. Hepatitis B or C must not have caused liver damage.
- Understand and sign the consent form. Follow birth control rules if you or your partner could become pregnant, and have a negative pregnancy test if you could become pregnant.
Who can't join
- Being pregnant or breastfeeding.
- Active lymphoma in the brain or spinal cord. A past history may be allowed.
- Graft-versus-host disease, where donor cells attack your body after a stem cell transplant, unless it only mildly affects the skin or does not need medicine that weakens the immune system throughout the body.
- An infection that is not improving despite proper treatment.
- A stroke or bleeding inside the skull within the past 6 months, or a brain or nervous system condition that would make treatment side effects hard to assess.
- Another past cancer, unless you have been free of it for more than 1 year. Some skin cancers, early cancers limited to the cervix or breast, and treated prostate cancer are exceptions.
- Being unable to meet the study’s rules for stopping other lymphoma treatments before cell collection, preparation chemotherapy, and CAR T-cell treatment.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
Inclusion Criteria: Patients eligible for study participation must meet all of the following criteria: 1. Disease Related Criteria Participants must have histologic confirmation of one of the following: 1. CD19+ aggressive non-Hodgkin lymphoma including any of the following subtypes * Diffuse Large B-cell Lymphoma, not otherwise specified * DLBCL, germinal-center B-cell type (GCB) * DLBCL, activated B-cell type (ABC) * T-cell histiocyte-rich B-cell lymphomas (THRBCL) * Primary cutaneous DLBCL, leg type * Intravascular large B cell lymphoma * EBV+ DLBCL, NOS * DLBCL associated with chronic inflammation * HHV8+ DLBCL, NOS * High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement(double hit lymphoma) * High grade B-cell lymphoma, NOS * Primary mediastinal B-cell lymphoma * B-cell Lymphoma, unclassifiable with features intermediate between DLBCL and Hodgkin lymphoma, as well as with features intermediate between DLBCL and Burkitt lymphoma * Follicular lymphoma grade 3B * Transformation of indolent lymphoma (i.e. CLL, MZL, FL, Waldenstrom's lymphoma,etc) to -diffuse large B-cell lymphoma * Burkitt Lymphoma * Lymphomatoid granulomatosis 2. CD19+ indolent non-Hodgkin lymphoma including any of the following subtypes: * Follicular lymphoma (grade 1-3A) * Marginal zone lymphoma: Including splenic marginal zone lymphoma, nodal marginal zone lymphoma, and mucosa associated lymphoid tissue (MALT) lymphoma * Waldenstrom's Macrogloublinemia * Nodular lymphocyte predominant hodgkin lymphoma (with documented CD19 expression) 3. Mantle cell Lymphoma 4. Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL) 2. Prior Therapy Criteria Prior/Concurrent Therapy Related Criteria (dependent upon subtype - see below) 1. Aggressive lymphoma: patients will qualify if any of the following scenarios are met below (radiation does not count as a line of therapy) * Relapse or persistent disease after ≥ 2 lines of systemic therapy OR * Refractory disease or relapse within 12 months of completion of 1st line systemic therapy OR * Refractory disease or relapse ≥ 1 line of therapy but not a candidate for autologous stem cell transplant * Patients with Burkitt lymphoma will qualify after ≥ 1 line of therapy regardless of the timing of relapse 2. Indolent lymphoma: * Relapse or persistent disease after ≥ 2 lines of systemic therapy. (Neither single agent rituximab or radiation qualify as a line of therapy.) 3. Mantle cell lymphoma: * Relapse or persistent disease after ≥ 1 line of systemic therapy. Neither single agent rituximab or radiation qualify as a line of therapy. 4. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma * Evidence of progression or intolerance after ≥ 2 lines of therapy. The following will qualify as a line of therapy for CLL/SLL: * systemic chemoimmunotherapy (e.g. BR, FCR, etc), * BTK inhibitor, BCL-2 inhibitor, * or PI3 Kinase inhibitor. * Neither single agent rituximab/obinutuzumab or radiation qualify as a line of therapy. 3. Clinical/Laboratory Criteria 1. Participants must be at least 18 years old 2. Participants must have a performance status of 0-2 on the ECOG scale 3. Participants must have adequate caregiving support for CAR T-cell therapy as determined by the PI/Co-I. 4. Participants must have measurable disease on cross section imaging by PET-CT and/or CT scans alone that is at least 1.5 cm in the longest diameter and measurable in two perpendicular dimensions as defined by IWG criteria. If participants with CLL do not have measurable disease on imaging, a bone marrow biopsy showing \> 5% CLL involvement in the bone marrow will qualify for enrollment 5. Participants that have received prior CD19 targeted therapy in the past they must have a tissue biopsy after completion of CD19 targeted therapy noting CD19 expression by either flowcytometry or immunohistochemistry (IHC). CD19 expression must be sufficient per PI/Co-I 6. Adequate organ function * Bone marrow function as evidenced by the following (unless directly attributable to disease within the bone marrow) within 14 days prior to registration. * Platelet count ≥ 50,000 cells/mm3 * ANC ≥ 750 cells/mm3 * Absolute lymphocyte count ≥ 150 cells/ mm3 * Hepatic function as evidenced by the following within 14 days prior to registration. * Serum bilirubin ≤ 1.5 X ULN unless attributed to Gilbert's syndrome or hemolysis or lymphoma involvement * Cardiac * No clinically significant ECG findings per PI/Co-I * Pulmonary * Oxygen saturation \> 90% on room air * Renal function as evidenced by the following within 14 days prior to registration. * Serum creatinine ≤ 2 mg/dL or creatinine clearance (as estimated by Cockcroft Gault Equation) ≥ 60 mL/min 7. Participants with hepatitis B virus infection must have undetectable viral load and on suppressive therapy within 14 days prior to registration and no evidence of HBV related hepatic damage. 8. Participants with Hepatitis C infection must have complete eradication therapy completed, have no evidence of HCV related damage and have undetectable viral load within 14 days of registration. 9. Participants with known human immunodeficiency virus (HIV)-infection must be receiving anti- retroviral therapy and have an undetectable viral load test within 14 days prior to registration. 10. WOCBP should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment. All men and women of childbearing potential must use acceptable methods of birth control throughout the study as described below. FCBP must have negative serum or urine pregnancy within 7 days prior to registration. 11. Men with female partners who are of childbearing potential: Recommendations for male and partner to use at least two effective contraceptive methods, as described above, during the study. 12. Participants are able to understand and voluntarily sign consent prior to any study related assessments or procedures are performed. Exclusion Criteria: Participants eligible for study participation CANNOT meet any of the following criteria: 1. Prior/Concurrent Therapy Related Criteria Guidelines regarding when lymphoma directed therapy should be stopped prior to leukapheresis, lymphodepleting chemotherapy, and CAR T-cell infusion are detailed in the protocol. These criteria must be planned to be met for all patients. 2. Clinical/Laboratory Criteria 1. Women who are pregnant or breast-feeding. 2. Participants with active CNS lymphoma. Participants can have a history of active CNS lymphoma as outline in protocol 3. Participants with evidence of Graft vs Host Disease from allogeneic stem cell transplant are ineligible unless it is either grade 1 involvement of the skin or not requiring systemic immunosuppression. 4. Participants with uncontrolled systemic fungal, bacterial or viral infection (defined as ongoing signs/symptoms related the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment) 5. Participants with a history of stroke or intracranial hemorrhage within 6 months prior to registration. Any CNS disorder that would serve as a major barrier in evaluating neurotoxicity/ICANS per enrolling physician 6. Participants with prior history of malignancy other than lymphoma unless subject is free of disease for more than 1 year from signing consent. Exceptions include the following: * Basal cell carcinoma of the skin * Squamous cell carcinoma of the skin * Carcinoma in situ of the cervix or breast * Previously treated localized prostate cancer with normal PSA levels 7. Participants with primary immunodeficiency or history of autoimmune disease (e.g. Crohn's, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression/systemic disease modifying agents within the last 1 year. 8. Participants with receipt of live vaccine within 28 days prior to registration. 9. Participants with history of autologous stem cell transplant within the last 60 days or allogeneic stem cell transplant within the last 90 days or CAR T-cell therapy within the last 180 days. 10. Participants with a history of severe immediate hypersensitivity reaction to any of the agents used in the study 11. Participants with any other illness that in the opinion of the investigator, would exclude the patient from participating in this study. 12. Participants must not have evidence of active CNS lymphoma involvement. This includes parenchymal, spinal cord, meningeal, or cerebrospinal fluid involvement. Patients with history of CNS involvement must have documented remission by contrast-enhanced MRI imaging and CSF evaluation for at least 60 days prior to registration. 13. Patients must not have any unstable angina, or myocardial infarction within the last 6 months, or symptoms consistent with NYHA CHF classification III or IV 14. Participants with receipt of live vaccine within 28 days prior to registration. 15. Participants with history of autologous stem cell transplant within the last 60 days or allogeneic stem cell transplant within the last 90 days or CAR T-cell therapy within the last 180days. 16. Participants with a history of severe immediate hypersensitivity reaction to any of the agents used in the study 17. Participants with any other illness that in the opinion of the investigator, would exclude the patient from participating in this study.
Study sites (1)
SC
- Hollings Cancer Center at Medical University of South Carolina · Charleston, SC 29425HCC Clinical Trials Office · Study contact · 843-792-9321 · hcc-clinical-trials@musc.eduBrian Hess, MD · Principal investigatorMore trials in Charleston