Study of CD19/CD22 Chimeric Antigen Receptor T Cells in Children & Young Adults w/ Recurrent or R… (NCT03241940) | Clinical Trial Compass
Active — Not RecruitingPhase 1
Study of CD19/CD22 Chimeric Antigen Receptor T Cells in Children & Young Adults w/ Recurrent or Refractory B Cell Malignancies
United States33 participantsStarted 2017-10-20
Plain-language summary
This phase I trial studies the best dose and side effects of CD19/CD22 chimeric antigen receptor (CAR) T cells when given together with chemotherapy, and to see how well they work in treating children or young adults with CD19 positive B acute lymphoblastic leukemia that has come back or does not respond to treatment. A CAR is a genetically-engineered receptor made so that immune cells (T cells) can attack cancer cells by recognizing and responding to the CD19/CD22 proteins. These proteins are commonly found on B acute lymphoblastic leukemia. Drugs used in chemotherapy, such as fludarabine phosphate and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving CD19/CD22-CAR T cells and chemotherapy may work better in treating children or young adults with B acute lymphoblastic leukemia.
Who can participate
Age range
1 Year – 30 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. 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 subjects must be either ineligible for allogeneic stem cell transplant (SCT), have refused SCT, recurred after SCT, or have disease activity that prohibits SCT at the time of enrollment.
. Chemotherapy refractory disease in subjects with B-ALL is defined as progression or stable disease after two lines of therapies
. Recurrence of disease after achieving a complete response (CR).
. Subjects 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.
. Subjects with Philadelphia Chromosome positive acute lymphoblastic leukemia (Ph+ALL) subjects are eligible if they progressed, had stable disease or relapsed after two lines of therapy, including tyrosine kinase inhibitors (TKIs).
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Since this is a Phase 1 trial that is no longer enrolling new patients, is there any way we could still access this CD19/CD22 CAR T-cell treatment — for example, through a compassionate use program or a follow-on study — or would a different trial be a better path for us right now?
2This trial targets both CD19 and CD22 on the cancer cells — how does that dual-target approach compare to single-target CAR T-cell therapies that might already be approved or available, and would either of those be a better fit given our specific situation?
3Because this is a Phase 1 study primarily designed to measure serious side effects and manufacturing success rather than to prove the treatment works, what does that mean for what we actually know so far about how well it controls the leukemia?
4The trial involves a chemotherapy preparative regimen before the CAR T-cell infusion — what are the risks of that 'lymphodepletion' chemotherapy on top of everything else, and how would you manage serious side effects like cytokine release syndrome if they occurred?
5Given that the trial was specifically looking at children and young adults with recurrent or refractory B-cell ALL, how does our current disease status — including any MRD results or Philadelphia chromosome findings — affect whether this type of treatment would even be worth pursuing at this stage?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Incidence and severity of dose limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD19/CD22 chimeric antigen receptor (CAR) T cells
Timeframe: Up to 28 days
2
Rate of successful manufacture and expansion of the CD19/CD22 chimeric antigen receptor (CAR) T cells to satisfy the targeted dose level and meet the required release specifications outlined in the Certificate of Analysis (COA)
Timeframe: 10-14 days after apheresis or thawing of cryopreserved peripheral blood mononuclear cell
. Subjects 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 Subjects with lymphoma must have progressed, had SD, or recurred after initial treatment regimens that include an anthracycline and an anti CD20 monoclonal antibody. Subjects who relapse ≥12 months after therapy should have progressed after autologous transplant or been ineligible for autologous transplant.
. 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. must be detected on greater than 50% of the malignant cells by immunohistochemistry or ≥ 90% by flow cytometry. The choice of whether to use flow cytometry or immunohistochemistry will be determined by what is the most easily available tissue sample in each subject. In general, immunohistochemistry will be used for lymph node biopsies, flow cytometry will be used for peripheral blood and bone marrow samples.
Exclusion criteria
. Recurrent or refractory ALL limited to isolated testicular.
. Subjects 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 treatment.
. 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 neurotoxicity.
. 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 involvement.