Anti-CD19 White Blood Cells for Children and Young Adults With B Cell Leukemia or Lymphoma
- Although progress has been made in treating children with B-cell cancers such as leukemia or lymphoma, many children do not respond to the standard treatments. One possible treatment involves collecting white blood cells called T cells from the person with cancer and modifying the cells to attack the B-cell cancer. The cells can then be given back to the participant. This study will use T cells that have been modified to attack the CD19 protein, which is found on the surface of some B-cell cancers.
- To see if anti-CD19 modified white blood cells are a safe and effective treatment for children and young adults with advanced B-cell cancer.
- Children and young adults between 1 and 30 years of age who have B-cell cancer (leukemia or lymphoma) that has not responded to standard treatments.
- The leukemia or the lymphoma must have the CD19 protein.
- There must be adequate organ function.
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies or bone marrow biopsies may be performed depending on the type of cancer.
- Participants will undergo a process where white blood cells are collected, called apheresis. These cells will be modified to contain the anti-CD19 gene.
- Participants will have 3 days of chemotherapy to prepare their immune system to accept the modified cells.
- Participants will receive an infusion of their own modified white blood cells. They will remain in the hospital until they have recovered from the treatment.
- Participants will have frequent follow-up visits to monitor the outcome of the treatment.
- If the participant benefits from the treatment, then he/she may have the option for another round of treatment.
B Cell Lymphoma
Large Cell Lymphoma
Genetic: Anti-CD 19 CAR Autologous PBL
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of T Cells Expressing an Anti-CD19 Chimeric Receptor in Children and Young Adults With B Cell Malignancies|
- To determine the safety and feasibility of administering escalating doses of anti- CD19-CAR engineered peripheral blood lymphocytes in two strata prior allogeneic stem cell transplant ASCT vs. no prior ASCT in children plus young adults with B c...
- To determine if administration of anti-CD19-CAR engineered peripheral blood lymphocytes can mediate antitumor effects in children with B cell malignancies
- To measure persistence of adoptively-transferred anti-CD19-CAR-transduced T cells in blood and CSF of patients
- Describe clinical impact
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Genetic: Anti-CD 19 CAR Autologous PBL
Chimeric antigen receptors (CAR) that recognize the CD19 antigen have been constructed and are in clinical trials at several institutions. In this trial, the POB will utilize a chimeric receptor containing the signaling domains of CD28 and CD3-zeta, currently under study in the CCR in adults, for children and young adults with CD19 expressing malignancies.
In co-cultures with CD19-expressing acute lymphoblastic leukemia cells, anti-CD19 CARtransduced T cells show robust killing, and in xenograft models, can rapidly clear CD19- expressing ALL cell lines.
Primary: To determine the safety and feasibility of administering escalating doses of anti- CD19-CAR engineered peripheral blood lymphocytes in two strata (prior allogeneic stem cell transplant SCT- vs. no prior SCT) of children and young adults with B cell malignancies following a cyclophosphamide/fludarabine preparative regimen.
Secondary: 1) To determine if the administration of anti-CD19-CAR engineered peripheral blood lymphocytes can mediate antitumor effects in children with B cell malignancies. 2) To measure persistence of adoptively-transferred anti-CD19-CAR-transduced T cells in the blood and CSF of patients.
Patients 1-30 years of age, at least 15 kg, with a CD19-expressing B-cell malignancy that has recurred after or not responded to one or more standard chemotherapy-containing regimens for their malignancy and is deemed incurable by standard therapy. Patients with a history of allogeneic SCT who meet all eligibility criteria are eligible to participate.
On Day 11 PBMC will be obtained by leukapheresis, CD3+ cells enriched and cultured in the presence of anti-CD3/-CD28 beads followed by retroviral vector supernatant containing the anti-CD19 CAR. Total culture time is 13 days.
On Day -4, 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 CD19-CAR cells will be infused on Day 0, with up to a 72h delay allowed for fresh cells or a 7 day delay if cells are cryopreserved, if needed for resolution of clinical toxicities or to generate adequate cell numbers.
A phase I cell dose escalation scheme will be performed using 3 dose levels (1 x 106 transduced T cells/kg; 3 x 106 transduced T cells/kg; 1 x 107 transduced T cells/kg) in two strata: patients who have undergone prior SCT and patients who have not previously undergone SCT. Three patients will be enrolled at each dose level, with the cohort expanded to 6 if dose limiting toxicity (DLT) occurs. If a cohort of patients previously treated with prior SCT completes a dose level without DLT, patients in the other stratum (without previous SCT) may dose escalate simultaneously. An expanded group of 12 patients at the maximum tolerated dose (MTD) or the highest dose achieved if no MTD was determined, will be accrued to provide additional information regarding the feasibility, safety and efficacy of this treatment.
Patients will be monitored for toxicity, response and T cell persistence.
|Contact: Cindy P Delbrook, R.N.||(301) firstname.lastname@example.org|
|Contact: Daniel W Lee, M.D.||(301) 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) NCI-1937|
|Principal Investigator:||Daniel W Lee, M.D.||National Cancer Institute (NCI)|