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New treatment option for Recurrent Transformed Chronic Lymphocytic Leukemia
Official title Zanubrutinib and Lisocabtagene Maraleucel for the Treatment of Richter's Syndrome
ClinicalTrials.gov ID: NCT05873712
What this study is testing
What is Cyclophosphamide?
Cyclophosphamide is an investigational medicine, given as an once-daily infusion into a vein, being studied as a potential treatment for recurrent transformed chronic lymphocytic leukemia.
Also referred to as (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate.
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 phase II trial tests how well zanubrutinib and lisocabtagene maraleucel (liso-cel) work together in treating patients with Richter's syndrome that has come back (recurrent) or does not respond to treatment (refractory). Richter's syndrome occurs when chronic lymphocytic leukemia and/or small lymphocytic leukemia transforms into an aggressive lymphoma, which is a cancer of the lymph nodes.
- Phase 2: a mid-size study of how well it works
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
- Diagnosis of RS - occurrence of diffuse large B-cell lymphoma (DLBCL) in patients with antecedent or concurrent CLL/SLL (CLL/SLL diagnosis per IWCLL...
- Must have relapsed/refractory disease as defined by one of the following:
- Participants must have undergone \>= 1 prior systemic therapeutic regimen administered for \>= 1 cycle for either CLL or RS, and have had either...
- Developed RS while receiving treatment for CLL
- Age \>= 18 years
You likely can't join if
- A history of treatment including any of the following: prior CD19 directed therapy, treatment with alemtuzumab within 6 months before enrollment...
- Prior allogeneic stem cell transplant with active graft-versus-host disease (GVHD), or requiring immunosuppressive drugs for treatment of GVHD, or...
- Inadequate recovery from adverse events related to prior therapy to grade =\< 1 (excluding grade 2 alopecia, neuropathy, and hypertension)
- Is unable to swallow oral medication, or has significant gastrointestinal disease that would limit absorption of oral medication
- Active bleeding or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease)
- Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP)
See the full eligibility criteria
Who can join
- Diagnosis of RS - occurrence of diffuse large B-cell lymphoma (DLBCL) in patients with antecedent or concurrent CLL/SLL (CLL/SLL diagnosis per IWCLL 2018 criteria).
- Must have relapsed/refractory disease as defined by one of the following:
- Participants must have undergone \>= 1 prior systemic therapeutic regimen administered for \>= 1 cycle for either CLL or RS, and have had either documented disease progression to the most recent treatment regimen, or...
- Developed RS while receiving treatment for CLL
- Age \>= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
- Total bilirubin =\< 2.0 times the institutional upper limit of normal (unless documented Gilbert's syndrome)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =\< 2.5 x institutional upper limit of normal
- Alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) =\< 2.5 x institutional upper limit of normal
- Creatinine clearance \>= 30 mL/min
- Using 24-hour creatinine clearance or standard Cockcroft-Gault equation
- Absolute lymphocyte count \> 100/uL at screening
- Left ventricular ejection fraction \>= 40% by multigated acquisition (MUGA) or echocardiogram (ECHO)
- Adequate bone marrow independent of growth factor support or infusion support at screening unless evidence shows that the cytopenia(s) is due to marrow involvement by CLL/small lymphocytic lymphoma (SLL). If cytopenias...
- Absolute neutrophil count (ANC) \>= 1000/mm\^3 (independent of growth factor support or infusion support at screening unless evidence shows that the cytopenia(s) is due to marrow involvement by CLL/SLL). If cytopenias...
- Platelets \>= 30,000/mm\^3 (independent of growth factor support or infusion support at screening unless evidence shows that the cytopenia(s) is due to marrow involvement by CLL/SLL). If cytopenias are due to disease in...
- Hemoglobin \>= 7 g/dL (independent of growth factor support or infusion support at screening unless evidence shows that the cytopenia(s) is due to marrow involvement by CLL/SLL). If cytopenias are due to disease in the...
- Radiographically measurable lymphadenopathy (or measurable extra-nodal disease) per Lugano criteria
- Must meet all institutional standards for receiving CAR T-cell therapy
- people (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, initiated prior to first dose of study...
- 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...
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:
- 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...
- With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 1 year after the human anti- CD19 CAR-T cell infusion or 1 month post last dose of zanubrutinib...
What rules you out
- A history of treatment including any of the following: prior CD19 directed therapy, treatment with alemtuzumab within 6 months before enrollment, prior allogeneic hematopoietic stem cell transplant (SCT) or donor...
- Prior allogeneic stem cell transplant with active graft-versus-host disease (GVHD), or requiring immunosuppressive drugs for treatment of GVHD, or have taken calcineurin inhibitors within 4 weeks prior to consent
- Inadequate recovery from adverse events related to prior therapy to grade =\< 1 (excluding grade 2 alopecia, neuropathy, and hypertension)
- Is unable to swallow oral medication, or has significant gastrointestinal disease that would limit absorption of oral medication
- Active bleeding or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease)
- Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP)
- Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening
- Clinically significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 or 4 cardiac disease as defined by the New...
- Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists
- Prothrombin time (PT)/international normalized ratio (INR) or activated partial thromboplastin time (PTT) (in the absence of lupus anticoagulant) \> 2 x upper limit normal (ULN)
- Treatment with a moderate or strong CYP3A inhibitor or inducer within 7 days prior to first dose of zanubrutinib
- Patients may not have an active intercurrent disease or concurrent malignancy that is expected to limit survival to \< 5 years
- Human immunodeficiency virus (HIV) seropositivity at screening
- people with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, unstable angina pectoris, pulmonary abnormalities or psychiatric illness/social situations that would limit...
- 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...
- Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy
- Serologic status reflecting active hepatitis B or C infection at screening. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative...
- History of autoimmune disease (i.e. rheumatoid arthritis, systemic lupus erythematosus) with requirement of immunosuppressive medication within 6 months
- Chronic use of corticosteroids \>= 20mg prednisone equivalent PO daily
- Live vaccines given in 28 days prior to lymphodepleting chemotherapy
The study team makes the final eligibility decision.
Where it's taking place
- New York, New York, United States
- Columbus, Ohio, United States
- Salt Lake City, Utah, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
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 New York, New York, United States; Columbus, Ohio, United States; Salt Lake City, Utah, United States. Enter your location above to see the nearest site and check your eligibility.
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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.