Anti-CD22 Chimeric Receptor T Cells in Pediatric and Young Adults With Recurrent or Refractory CD22-expressing B Cell Malignancies
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02315612|
Recruitment Status : Recruiting
First Posted : December 12, 2014
Last Update Posted : December 19, 2020
- One type of cancer therapy takes blood cells from a person, changes them in a lab, then gives the cells back to the person. In this study, researchers are using an anti-CD22 gene, a virus, and an immune receptor to change the cells.
- To see if giving anti-CD22 Chimeric Antigen Receptor (CAR) cells to young people with certain cancers is safe and effective.
- People ages 1-30 with a leukemia or lymphoma that has not been cured by standard therapy.
- Participants will be screened to ensure their cancer cells express the CD22 protein. They will also have medical history, physical exam, blood and urine tests, heart tests, scans, and x-rays. They may give spinal fluid or have bone marrow tests.
- Participants may have eye and neurologic exams.
- Participants will get a central venous catheter or a catheter in a large vein.
- Participants will have white blood cells removed. Blood is removed through a needle in an arm. White blood cells are removed. The rest of the blood is returned by needle in the other arm.
- The cells will be changed in a laboratory.
- Participants will get two IV chemotherapy drugs over 4 days. Some will stay in the hospital for this.
- All participants will be in the hospital to get anti-CD22 CAR cells through IV. They will stay until any bad side effects are gone.
- Participants will have many blood tests. They may repeat some screening exams.
- Participants will have monthly visits for 2-3 months, then every 3-6 months. They may repeat some screening exams.
- Participants will have follow-up for 15 years.
|Condition or disease||Intervention/treatment||Phase|
|Follicular Lymphoma ALL NHL Large Cell Lymphoma||Biological: CD22-CAR||Phase 1|
- Adoptive cellular therapy with T cells genetically modified using viral-based vectors to express chimeric antigen receptors targeting the CD19 molecule have demonstrated dramatic clinical responses in patients with acute lymphoblastic leukemia (ALL). However, not all patients respond and CD19-negative escape has been observed following CD19 CAR therapy, as well as anti-CD19/CD3 bispecific antibody therapy. Thus, additional targets are needed.
- CD22 is a B-lineage-restricted, transmembrane phosphoglycoprotein of the Ig superfamily that is widely expressed on B-cell malignancies including 96% to 100% of pediatric Bprecursor ALL. Therefore, CD22 represents a promising target. Encouraging responses targeting CD22 with an antibody based immunoconjugate have been seen in patients, including children, with recurrent and refractory ALL. This will be the first in human testing of anti-CD22 CAR adoptive cell therapy.
- To determine the feasibility of producing anti-CD22 CAR cells meeting established release criteria. Complete
- To assess the safety of administering escalating doses of anti-CD22-CAR engineered T cells in children and young adults with recurrent or refractory CD22- expressing B cell malignancies following a cyclophosphamide/fludarabine preparative regimen.
- Patients 3-30 years of age, at least 14.5 kg, with CD22-expressing B-cell malignancies that have recurred after or not responded to one or more standard regimens and deemed incurable by standard therapy. Patients with a history of allogeneic hematopoietic transplantation (SCT) who meet all eligibility criteria are eligible to participate. Patients previously treated with anti-CD19 CAR engineered T cells are also eligible.
- PBMC will be obtained by leukapheresis, CD3+ cells enriched and cultured in the presence of anti-CD3/-CD28 beads followed by lentiviral vector supernatant containing the anti-CD22 (M971BBz) CAR.
- On Day -4 (cell infusion is Day 0), patients will begin induction chemotherapy comprising fludarabine 25 mg/m2 on Days -4, -3 and -2 and cyclophosphamide 900 mg/m2 on day 2.
- The CD22-CAR cells will be infused on Day 0, with up to a 72h delay allowed for infusion of fresh cells or a 7 day delay if cells are cryopreserved, if needed for resolution of clinical toxicities, to generate adequate cell numbers, or to facilitate scheduling.
- A phase I cell dose escalation scheme will be performed using 3 dose levels (3 x 10(5) transduced T cells/kg; 1 x 10(6) transduced T cells/kg; and 3 x 10(6) transduced T cells/kg;). If 2/6 patients have DLT at dose level 1, safety will be evaluated in a de-escalated dose of 1 x 10(5) transduced T cells/kg (more or less 20%)). Once the maximum tolerated dose (or highest level evaluated) is reached, enrollment into an expansion cohort of a total of 58 patients at MTD in (32 with and 26 without previous CD19 CAR T cells) will proceed to provide additional information regarding the feasibility, safety and efficacy of this treatment. Patients who have previously received CD19 CAR T cells will be evaluated separately from CAR-na(SqrRoot) ve patients as response may be different in these two groups.
- Patients will be monitored for toxicity, response and T cell persistence as well as other biologic correlates.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||126 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Dose Escalation Study of Anti-CD22 Chimeric Receptor T Cells in Pediatric and Young Adults With Recurrent or Refractory CD22-expressing B Cell Malignancies|
|Actual Study Start Date :||December 12, 2014|
|Estimated Primary Completion Date :||June 1, 2025|
|Estimated Study Completion Date :||June 1, 2040|
Experimental: Arm 1
Dose escalation of CD22-CAR
CD22-CAR cells will be infused on Day 0 after induction chemotherapy regimen.
Experimental: Arm 2
Dose expansion of CD22-CAR
CD22-CAR cells will be infused on Day 0 after induction chemotherapy regimen.
- Toxicity [ Time Frame: End of treatment ]Number of patients who have grade 3 CRS and above
- Response [ Time Frame: 1 month, 3 months, and 6 months following CAR infusion ]Number of patients who have complete and partial remission
- Safety and Toxicity [ Time Frame: 1 month, 3 months and 6 months following CAR infusion ]Number of patients who have detectable CAR cells
- Objective Response (Complete + Partial Remission) [ Time Frame: 1 month, 3 months and 6 months following CAR infusion ]The number of patients who have complete and partial remissions
- CAR-T cell Persistence [ Time Frame: 1 month, 3 months and 6 months following CAR infusion ]The number of patients who have detectable CAR cells
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02315612
|Contact: NCI Pediatric Leukemia Lymphoma BMT Team||(240) firstname.lastname@example.org|
|Contact: Nirali N Shah, M.D.||(240) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Nirali N Shah, M.D.||National Cancer Institute (NCI)|