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New treatment option for Mantle Cell Lymphoma
Official title Study of Kappa Chimeric Antigen Receptor (CAR) T Lymphocytes Co-Expressing the Kappa and CD28 CARs for Relapsed/Refractory Kappa+ Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.
ClinicalTrials.gov ID: NCT04223765
What this study is testing
What is CAR.k.28?
CAR.k.28 is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for mantle cell lymphoma.
Also referred to as Kappa Chimeric Antigen Receptor and CD28 Endodomain.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This study will combine both T cells and antibodies in order to create a more effective treatment. The treatment tested in this study uses modified T-cells called Autologous T Lymphocyte Chimeric Antigen Receptor (ATLCAR) cells targeted against the kappa light chain antibody on cancer cells.
- Phase 1: an early, usually small safety study
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Note: During the period of cell procurement and CAR.κ.28 T cell production, people are allowed to receive additional standard of care chemotherapy to...
- Written informed consent and HIPAA authorization for release of personal health information.
- Adults ≥18 years of age.
- Diagnosis of relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma OR histologically confirmed B-cell NHL, including the...
- DLBCL not otherwise specified (NOS)
You likely can't join if
- for the Study people meeting any of the following exclusion criteria will not be able to participate in this study (procurement, lymphodepletion and...
- Subject has signed a consent to undergo cell procurement.
- Evidence of adequate organ function as defined by:
- Total bilirubin \ 1.5 mg/dL if their conjugated bilirubin is \<1.5 × ULN)
- AST and ALT \< 5x ULN
- Pulse oximetry of \>90% on room air
See the full eligibility criteria
Who can join
- Note: During the period of cell procurement and CAR.κ.28 T cell production, people are allowed to receive additional standard of care chemotherapy to stabilize their disease if the treating physician feels it is in the...
- Written informed consent and HIPAA authorization for release of personal health information.
- Adults ≥18 years of age.
- Diagnosis of relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma OR histologically confirmed B-cell NHL, including the following types defined by WHO 2016: Aggressive Lymphomas:
- DLBCL not otherwise specified (NOS)
- T cell/histiocyte rich large B cell lymphoma; primary cutaneous DLBCL, leg type; EBV-positive DLBCL NOS; DLBCL associated with chronic inflammation; Lymphomatoid granulomatosis; Large B-cell lymphoma with IRF4...
- Primary mediastinal (thymic) large B-cell lymphoma
- High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement; high grade B-cell lymphoma, NOS
- B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma
- Transformation of indolent lymphoma or CLL to DLBCL will also be included
- Burkitt lymphoma Indolent Lymphomas:
- Follicular lymphoma grade 1-3b
- Splenic marginal zone lymphoma
- Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue
- Nodal marginal zone lymphoma
- Mantle cell lymphoma
- people with central nervous system (CNS) disease will not be excluded as long as it has been stable for 3 months people with bone marrow only involvement are eligible
- people relapsed after autologous or allogeneic stem cell transplant are eligible for this study.
- people who have received prior CD19-directed CAR therapies for relapsed/refractory disease are eligible for this study. However, at least 3 months must have passed since the subject received CD19 CAR-T cells.
- Patients with aggressive lymphomas must have relapsed or refractory disease after having received at least 2 prior lines of systemic therapy, including, at a minimum:
- An anti-CD20 monoclonal antibody
- An anthracycline containing chemotherapy regimen (if eligible)
- An autologous stem cell transplant (if eligible)
- For indolent lymphomas, people must have received at least 2 prior lines of therapy for their lymphoma
- people with specifically relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma must have received at least 2 prior therapy regimens which can include, but not limited to:
- A combination of an anti-CD20 monoclonal antibody and an alkylating agent, OR
- A Bruton's Tyrosine Kinase Inhibitor, OR
- A BCL-2 inhibitor in combination with an anti-CD20 monoclonal antibody
- people with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or how well it works assessment of the investigational regimen are eligible for...
- Kappa-positive expression on lymphoma or CLL/SLL tissue sample, or kappa restriction on flow cytometry (archival or fresh) as confirmed by institutional hematopathology standard (result must be confirmed at the time of...
- Karnofsky score of \> 60%
- Female people of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study, and for 6 months after the study is...
What rules you out
- for the Study people meeting any of the following exclusion criteria will not be able to participate in this study (procurement, lymphodepletion and cell infusion): 1\. A history of intolerance to bendamustine or...
- Subject has signed a consent to undergo cell procurement.
- Evidence of adequate organ function as defined by:
- Total bilirubin \ 1.5 mg/dL if their conjugated bilirubin is \<1.5 × ULN)
- AST and ALT \< 5x ULN
- Pulse oximetry of \>90% on room air
- Creatinine ≤ 2 x ULN
- Imaging results from within 120 days prior to procurement to assess presence of active disease.
- Confirmed kappa-positive expression on lymphoma or CLL/SLL tissue or bone marrow sample (archival or fresh) as confirmed by pathology.
- Subject has adequate cardiac function, defined as:
- No ECG evidence of acute ischemia
- No ECG evidence of active, clinically significant conduction system abnormalities
- Prior to study entry, any ECG abnormality at screening not felt to put the subject at risk has to be documented by the investigator as not medically significant
- No uncontrolled angina or severe ventricular arrhythmia
- Left ventricular ejection fraction (LVEF) \>40% as measured by ECHO, with no additional evidence of decompensated heart failure, performed within 30 days prior to procurement
- In women of child-bearing potential, negative serum pregnancy test within 72 hours prior to procurement or documentation that the subject is post-menopausal. Post-menopausal status must be confirmed with documentation...
- Written informed consent to enroll in the CAR-T cell therapy trial must be obtained prior to lymphodepletion.
- The last bridging therapy should be completed at least 3 weeks prior to lymphodepletion.
- people who have received bridging therapy will be reassessed with imaging within 5 days prior to lymphodepletion and at least 3 weeks after bridging therapy. If a patient did not receive bridging chemotherapy, they will...
- Adequate organ function per the following criteria are required prior to lymphodepletion:
- Adequate bone marrow function, as defined by:
- ANC \>1.0 × 109/L
- Platelets \>50 × 109/L unless related to lymphoma involvement (independent of transfusion within 7 days of lymphodepletion)
- Total bilirubin ≤1.5 × ULN (people with Gilbert's syndrome may be enrolled despite a total bilirubin level \>1.5 mg/dL if their conjugated bilirubin is \<1.5× ULN)
- AST and ALT ≤ 5× ULN
- Pulse oximetry of \> 90% on room air
- Creatinine ≤2 x ULN
- If people display any clinical signs or symptoms of cardiac dysfunction after receiving bridging chemotherapy, they will undergo repeat ECG and ECHO to reassess their cardiac function and status
- In female people of childbearing potential, a negative serum pregnancy test within 72 hours prior to l ymphodepletion or documentation that the subject is post-menopausal or has been surgically sterilized...
- In people with CLL/SLL, a bone marrow biopsy within 28 days prior to lymphodepletion.
- In people with WM/LPL, a bone marrow biopsy within 90 days prior to lymphodepletion.
- people must have autologous transduced activated T-cells that meet the Certificate of Analysis (CofA) acceptance criteria.
- Has not received any tumor vaccines within the previous six weeks prior to lymphodepletion.
- Has not received investigational agent or cancer-directed therapy within the previous 3 weeks, or 5 half-lives (whichever is shorter), prior to lymphodepletion.
- people may not be receiving strong inhibitors of CYP1A2 (e.g., fluvoxamine, ciprofloxacin) up through 72 hours after the last dose of bendamustine, as these may increase plasma concentrations of bendamustine, and...
- Subject is not taking a prohibited or contraindicated medication listed in the protocol. Contraindicated medications should be discontinued at least two weeks prior to the scheduled lymphodepletion or by at least 5...
- No evidence of uncontrolled infection or sepsis. Eligibility Criteria to be Met Prior to Cell Infusion After Lymphodepletion
- No evidence of uncontrolled infection or sepsis.
- Evidence of adequate organ function as defined by:
- Total bilirubin ≤2 × ULN, unless attributed to Gilbert's syndrome
- AST \< 5 × ULN
- ALT \< 5 × ULN
- Creatinine ≤ 3 x ULN
- Subject has no clinical indication of rapidly progressing disease in the opinion of the clinical investigator.
- Subject is a good candidate for treatment with CAR.κ.28 cell product per the clinical investigator's discretion.
The study team makes the final eligibility decision.
Where it's taking place
- Chapel Hill, North Carolina, United States
Compensation & support
A stipend or compensation may be offered.
Compensation mentioned.
ClinicalTrials.gov doesn't provide a reliable structured field for payment or travel support - confirm details with the study team.
Questions & answers
Do participants get paid in this trial?
This study's listing includes signals that participants may be compensated or receive a stipend. Amounts vary and are set by the study team - confirm the details with them.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Chapel Hill, North Carolina, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.