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New treatment option for Acute Lymphoblastic Leukemia, Adult B-Cell
Official title Fourth-gen CAR T Cells Targeting CD19/CD22 for Highly Resistant B-cell Lymphoma/Leukemia (PMBCL/CNS-BCL).
ClinicalTrials.gov ID: NCT06213636
What this study is testing
What is CD19/CD22-CAR T cells?
CD19/CD22-CAR T cells is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for acute lymphoblastic leukemia, adult b-cell.
Also referred to as EB-BH2024.
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 is an open-label, single-arm, phase I clinical trial with dose escalation designed to investigate the safety, tolerability, and pharmacokinetic properties of Human CD19-CD22 Targeted T Cells Infusion. The primary objectives are to preliminarily assess the impact of Human CD19-CD22 Targeted T Cells Infusion in patients with relapsed/refractory B-cell acute lymphoblastic leukemia and to explore the appropriate dose and reinfusion schedule for phase II.
- 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 2 to 90
You may be able to join if
- Diagnosis: ALL In view of the PI and the primary oncologist, there must be no available alternative curative therapies or subject has declined to...
- Chemotherapy refractory disease in people with B-ALL is defined as progression or stable disease after two lines of therapies
- Recurrence of disease after achieving a complete response (CR).
- people with persistent or relapsed minimal residual disease (MRD) (by flow cytometry, PCR, FISH, or next generation sequencing) require verification...
- people with Philadelphia Chromosome positive acute lymphoblastic leukemia (Ph+ALL) people are eligible if they progressed, had stable disease or...
You likely can't join if
- people meeting any of the following criteria are not eligible for participation in the study:
- Recurrent or refractory ALL limited to isolated testicular.
- people with radiologically-detected CNS lymphoma or CNS 3 disease (presence of ≥ 5/µL WBCs in CSF and cytospin positive for blasts [in the absence of...
- Hyperleukocytosis (≥ 50,000 blasts/µL) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability...
- History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 3...
- Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple UTI and...
See the full eligibility criteria
Who can join
- Diagnosis: ALL In view of the PI and the primary oncologist, there must be no available alternative curative therapies or subject has declined to pursue alternative therapy; and people must be either ineligible for...
- Chemotherapy refractory disease in people with B-ALL is defined as progression or stable disease after two lines of therapies
- Recurrence of disease after achieving a complete response (CR).
- people with persistent or relapsed minimal residual disease (MRD) (by flow cytometry, PCR, FISH, or next generation sequencing) require verification of MRD positivity on two occasions at least 4 weeks apart.
- people with Philadelphia Chromosome positive acute lymphoblastic leukemia (Ph+ALL) people are eligible if they progressed, had stable disease or relapsed after two lines of therapy, including tyrosine kinase inhibitors...
- people with recurrence of isolated CNS relapse after achieving complete remission (CR); if relapsed with MRD, will require verification of MRD positivity on two occasions at least 4 weeks apart.
- Diagnosis: Lymphoma people with lymphoma must have progressed, had SD, or recurred after initial treatment regimens that include an anthracycline and an anti CD20 monoclonal antibody. people who relapse ≥12 months after...
- CD19 expression CD19 expression is required at any time since diagnosis. If patient has received anti-CD19 targeted therapy (i.e. Blinatumomab), then CD19 expression must be subsequently demonstrated. CD19 expression...
- people who have undergone autologous SCT with disease progression or relapse following SCT will be eligible if all other eligibility criteria are met. people who have undergone allogeneic SCT will be eligible if, in...
- people who have undergone prior anti-CD19 or anti-CD22 CAR therapy will be eligible if \< 5% of circulating levels of CD3+ cells express the previous CAR by flow cytometry.
- Must have evaluable or measurable disease; people with lymphoma must have evaluable or measurable disease according to the revised IWG Response Criteria for Malignant Lymphoma[66] must be present. Lesions that have been...
- At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune...
- Exceptions:
- There is no time restriction with regard to prior intrathecal chemotherapy (incl. steroids) provided there is complete recovery from any acute toxic effects of such; g. people receiving hydroxyurea may be enrolled...
- people receiving steroid therapy at physiologic replacement doses (≤ 5 mg/day of prednisone or equivalent doses of other corticosteroids) only are allowed provided there has been no increase in dose for at least 2 weeks...
- Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for clinically non-significant toxicities, such as alopecia, nutritional support measures, electrolyte abnormalities, or those not...
- Age Greater than or equal to 1 year of age and less than or equal to 30 years of age at time of enrollment; must meet parameters for apheresis per institutional guidelines. NOTE: The first subject in the first dose...
- Performance Status: people \> 10 years of age: Karnofsky ≥ 50%; people ≤ 10 years of age: Lansky scale ≥ 50% (See Appendix B Section 14.2)
- Normal Organ and Marrow Function (supportive care is allowed per institutional standards, i.e. filgrastim, transfusion)
- ANC ≥750/uL\
- Platelet count ≥50,000/uL\
- Absolute lymphocyte count ≥150/uL\
- Adequate renal, hepatic, pulmonary and cardiac function defined as:
- Serum ALT/AST ≤10 ULN (unless elevated ALT/AST is attributed to leukemia or lymphoma involvement of the liver, in which case this criterion will be waived and not disqualify a patient).
- Total bilirubin ≤1.5 mg/dl, except in people with Gilbert's syndrome.
- Cardiac ejection fraction ≥ 45%, no evidence of physiologically significant pericardial effusion as determined by an ECHO, and no clinically significant ECG findings
- No clinically significant pleural effusion
- Baseline oxygen saturation \>92% on room air at rest
- creatinine: within age adjusted normal institutional limits (see table below) OR
- creatinine clearance ≥60 mL/min/1.73 m2 (as estimated by Cockcroft Gault Equation) for people with creatinine levels above institutional normal.
- Age (Years) Maximum Serum Creatinine (mg/dL) -≤5 0.8 5 \ 10 1.2
- if these cytopenias are not judged by the investigator to be due to underlying disease (i.e. potentially reversible with anti-neoplastic therapy); A subject will not be excluded because of pancytopenia ≥ Grade 3 if it...
- CNS Status
- people with ALL
- people with the following CNS status are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy:
- CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of WBCs;
- CNS 2, defined as presence of \ 5/µL WBCs but negative by Steinherz/Bleyer algorithm: CNS 2a: \<10/µL RBCs; \< 5/µL WBCs and cytospin positive for blasts; CNS 2b: ≥10/µL RBCs; \< 5/µL WBCs and cytospin positive for...
- people with lymphoma
- people must have no signs or symptoms of CNS disease or detectable evidence of CNS disease on MRI at the time of screening. people who have previously been treated for CNS disease and who have the following CNS status...
- CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of WBCs;
- CNS 2, defined as presence of \ 5/µL WBCs but negative by Steinherz/Bleyer algorithm:
- CNS 2a: \< 10/µL RBCs; \< 5/µL WBCs and cytospin positive for blasts;
- CNS 2b: ≥ 10/µL RBCs; \< 5/µL WBCs and cytospin positive for blasts;
- CNS 2c: ≥ 10/µL RBCs; ≥ 5/µL WBCs and cytospin positive for blasts but negative by Steinherz/Bleyer algorithm.
- Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of...
- Contraception people of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four (4) months after receiving the preparative regimen.
- Females of child-bearing potential must have a negative pregnancy test because of the potentially dangerous/unknown effects on the fetus.
- Ability to give informed consent. All people ≥ 18 years of age must be able to give informed consent. For people \ 7 years of age, when appropriate.
What rules you out
- people meeting any of the following criteria are not eligible for participation in the study:
- Recurrent or refractory ALL limited to isolated testicular.
- people with radiologically-detected CNS lymphoma or CNS 3 disease (presence of ≥ 5/µL WBCs in CSF and cytospin positive for blasts [in the absence of a traumatic lumbar puncture] and/or clinical signs of CNS leukemia).
- Hyperleukocytosis (≥ 50,000 blasts/µL) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy.
- History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 3 years.
- Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active...
- Ongoing infection with HIV or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive) as the immunosuppression contained in this study will pose unacceptable risk. A history of hepatitis B or hepatitis C...
- CNS disorder such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or autoimmune disease with CNS involvement that in the judgment of the investigator may impair the ability to evaluate...
- History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment, or have cardiac atrial or cardiac ventricular lymphoma...
- people receiving anticoagulation therapy.
- Any medical condition that in the judgement of the principal investigator is likely to interfere with assessment of safety or how well it works of study treatment
- History of severe immediate hypersensitivity reaction to any of the agents used in this study.
- Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the conditioning lymphodepletion chemotherapy on the fetus or infant. Females who have undergone...
- In the investigator's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.
- May not have primary immunodeficiency or history of systemic autoimmune disease (e.g. Crohns, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease...
The study team makes the final eligibility decision.
Where it's taking place
- Beijing, Beijing Municipality, China
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, 2 years to 90 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Beijing, Beijing Municipality, China. 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.