Background:
Acute lymphoblastic leukemia (ALL) is a type of blood cancer. Chimeric antigen receptor
(CAR) therapy involves taking immune cells (T cells) from a person and modifying them to
better target cancer cells. CAR T-cell therapy that targets a marker called CD19 has been
show to can cure ALL in many children and adults. But in about 50% of patients, the ALL
comes back within a year. Researchers want to find out if a second treatment with CAR
T-cell therapy that targets a different marker, CD22, can keep the cancer away longer.
Objective:
To see if CD22 CAR T-cell therapy can keep ALL away longer.
Eligibility:
People aged 3 to 65 years who have no signs of cancer after CD19 CAR T-cell treatment for
ALL.
Design:
Participants will be screened. They will have imaging scans and tests of their heart
function. A sample of tissue (biopsy) will be collected from their bone marrow. They will
have a fluid sample collected from the area around their spinal cord.
Participants will undergo collection of their white blood cells (T cells) during a
procedure called leukapheresis. Blood will be taken from their body through a vein. The
blood will pass through a machine that separates out the T cells. The remaining blood
will be returned to the body through a different vein. The cells will be altered in a lab
to create CD22 CAR T-cell therapy.
Participants will take drugs over 4 consecutive days to prepare their body for the CAR
T-cell therapy; then they will receive their modified T cells through a tube inserted
into a vein. Some people may need to stay in the hospital during treatment.
Participants will have follow-up visits for 2 years.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07328503.
Background:
- Despite impressive cure rates in children and young adults with B-cell acute
lymphoblastic leukemia (B-ALL) generally, patients with relapsed/refractory disease
have historically suffered from limited treatment options. CD19 and CD22 chimeric
antigen receptor (CAR) T-cells are effective at inducing remission in the majority
of children and young adults with relapsed/refractory B-ALL.
- However, remissions are often not durable, and many patients will relapse in the
absence of a consolidative hematopoietic stem cell transplant (HSCT), which is
associated with high morbidity and mortality.
- Leukemic antigen escape has led to the interest in multi-antigen targeting
approaches, targeting both CD19 and CD22 to enhance the long-term effectiveness of
CAR T-cells. We have previously treated patients on phase 1/2 clinical trials using
a bivalent CD19/22 CAR T-cell as well as a bicistronic CD19xCD22 CAR T-cell as
combinatorial strategies.
- Some of the best long-term results in the literature have been seen with co-infusion
of CD19 and CD22 CAR T-cells. Three FDA-approved CD19 CAR T-cell products are
available commercially, and our phase 1/2 trial of CD22 CAR T-cells has demonstrated
efficacy and safety.
- The use of CD22 CAR T-cells as consolidation of CD19 CAR T-cell-induced remission
offers the potential to extend the durability of remission while limiting the
toxicity associated with HSCT.
Objective:
-To determine the 1-year relapse-free survival (RFS) from the time of CD22 CAR T-cell
infusion.
Eligibility:
-Participants aged 3-65 years who have relapsed/refractory B-ALL with a history of
demonstrated expression of CD19 and CD22 and have achieved an MRD-negative remission
after receiving an FDA-approved CD19 CAR T-cell product.
Design:
- Single-arm study with 4 days lymphodepleting preparative regimen, including
fludarabine and cyclophosphamide, followed by CD22 CAR T-cells administration.
- Participants will be evaluated for toxicity, antitumor effects, CAR expansion and
persistence, and other biological correlatives for 2 years after cell infusion.
- The trial will accrue 16 evaluable participants. The accrual ceiling for the trial
is 20 participants to account for inevaluable participant and screen failures.
Lead OrganizationNational Cancer Institute
Principal InvestigatorSara Kate Silbert
