T-Lymphocytes Genetically Targeted to the B-Cell Specific Antigen CD19 in Pediatric and Young Adult Patients With Relapsed B-Cell Acute Lymphoblastic Leukemia
A Phase I Trial of T-Lymphocytes Genetically Targeted to the B-Cell Specific Antigen CD19 in Pediatric and Young Adult Patients With Relapsed B-Cell Acute Lymphoblastic Leukemia
1 other identifier
interventional
23
1 country
2
Brief Summary
The purpose of this study is to test the safety of giving the patient special cells made from their own blood called "Modified T-cells". The goal is to find a safe dose of modified T-cells for patients whose leukemia has returned to the bone marrow.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started May 2013
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2013
CompletedFirst Submitted
Initial submission to the registry
May 21, 2013
CompletedFirst Posted
Study publicly available on registry
May 23, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2026
CompletedJune 5, 2025
June 1, 2025
13 years
May 21, 2013
June 4, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
safety
of gene-modified autologous T cells targeted to CD19 and infused into patients with relapsed/refractory B- ALL. Toxicities will be graded on a scale of 1 to 5 as described by the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Adverse Events/Toxicities will be graded/attributed starting at time of T cell infusion and continue for up to 30 days or until modified T cells are no longer present.
1 year
Secondary Outcomes (2)
assess the persistence of modified T cells
1 year
the development of B cell aplasia
1 year
Study Arms (2)
Cohort 1 (MRD)
EXPERIMENTALPatients with no morphologic evidence of disease at the time of T cell infusion, (\<5% blasts in the bone marrow) as assessed by morphology or flow cytometry. Participating site PI to determine cohort stratification in the event of morphology/flow cytometry blast count discrepancy. Cohort 1 patients will receive conditioning chemotherapy followed by 1x10\^6 19-28z+ T cells/kg over 1 to 2 days. During formulation of End of Production (EOP) T cells, under or over estimation of CAR modified T-cells may occur. Patients may receive an altered fractionation of the total doses (e.g. ½ on Day 0 and ½ on Day +1) or up to 35% over total cell dose with approval by the participating site PI. In both cohorts, patients will be allowed to receive a 2nd treatment of 19-28z+ T cells if they benefited from the first infusion and did not experience any non-hematologic grade 4 toxicities.
Cohort 2 (Morphologic Disease)
EXPERIMENTALPts with morphologic evidence of disease at the time of T cell infusion, (≥5% blasts in the bone marrow) as assessed by morphology or flow cytometry. Participating site PI to determine cohort stratification in the event of morphology/flow cytometry blast count discrepancy. Pts with increased blasts (5-10% blasts) that are immunophenotypically consistent with recovering marrow from prior re-induction chemo may be treated under Cohort 1 with approval of the participating site PI. Cohort 2 pts will get conditioning chemo followed by 1x10\^6 19-28z+ T cells/kg over 1 to 2 days. During formulation of EOP T cells, under or over estimation of CAR modified T-cells may occur. Pts may get up to 35% over total cell dose with approval by the participating site PI. Both cohorts, pts will be allowed to receive a 2nd treatment of 19-28z+ T cells if they benefited from the first infusion \& did not experience any non-hematologic grade 4 toxicities.
Interventions
Eligibility Criteria
You may qualify if:
- Age \< 26 years, whose disease meets one of the following 3 criteria:
- VHR\*
- Patients in 1st or subsequent marrow relapse (isolated or combined), at the time of relapse, during retrieval therapy, or after achievement of CR.
- Refractory disease \*Definitions of VHR B-ALL include the following:
- NCI HR-ALL and age ≥ 13 years at diagnosis
- CNS-3 leukemia at diagnosis
- Day 29/End of Induction BM MRD \> 0.01%
- Induction failure (M3 BM at Day 29/End of Induction)
- Hypodiploidy (n\< 44 chromosomes and/or a DNA index \< 0.81)
- t(9;22) ALL (Philadelphia Chromosome/Ph+ ALL)
- t(17;19) ALL or Ph-Like ALL
- MLL gene rearrangement
- IKZF1 deletions
- Intrachromosomal amplification of chromosome 21 (iAMP21) Please note patients that only meet the criteria for collection/storage of PBMCs will need to be reconsented prior to infusion of genetically modified T-cells.
- Patients must have a history of relapsed/refractory CD19+ B-ALL involving the marrow to be eligible for infusion of modified T cells.
- +14 more criteria
You may not qualify if:
- Karnofsky/Lansky performance status \<60.
- Patients with any concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation
- Patients with active HIV, hepatitis B or hepatitis C infection.
- Females who are pregnant
- Karnofsky/Lansky performance status \<60.
- Patients with any concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation
- Patients will be excluded if they have isolated extra-medullary relapse of ALL
- Females who are pregnant.
- Patients with active (grade 2-4) acute graft versus host disease (GVHD), chronic GVHD or an overt autoimmune disease (e.g. hemolytic anemia) following allo-HSCT requiring glucocorticosteroid treatment (\>0.5 mg/kg/day prednisone or its equivalent) as treatment.
- o If the LP is traumatic (containing RBCs) and cannot be repeated the Steinherz/Bleyer ratio will be used to determined unequivocal evidence of CSF leukemia at the discretion of the treating physician.
- Uncontrolled, symptomatic, intercurrent illness including but not limited to infection, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the treating investigator would pose an unacceptable risk to the subject.
- Prior neurologic toxicity to previous immunotherapy
- Preceding and/or ongoing organ dysfunction or other co-morbidity including but not limited to uncontrolled infection that would impair the patient's ability to endure known side effects of cytokine release syndrome or neurologic toxicity
- Recent prior therapy: Systemic chemotherapy less than 2 weeks prior to infusion or apheresis (6 weeks for clofarabine or nitrosoureas for apheresis) or radiation therapy less than or equal to 3 weeks prior to apheresis. Exceptions:
- oThere is no time restriction in regard to prior intrathecal chemotherapy provided there is complete recovery from any acute toxic effects of such.
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Dana-Farber Cancer Institute:Dana- Farber/Children's Hospital
Boston, Massachusetts, 02115, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Related Publications (2)
Valtis YK, Lin C, Nemirovsky D, Devlin SM, Rejeski K, Curran KJ, Wang X, Shah NN, Jeyakumar N, Miller K, Zhang A, Kota VK, Al Darobi A, Muhsen IN, Sasine JP, Aldoss I, Advani AS, Reshef R, Chen EC, Kopmar NE, Tsai SB, Hilal T, Shah BD, Faramand RG, Solh MM, Tan V, Bezerra ED, Battiwalla M, Ramakrishnan A, Mathews J, Shaughnessy PJ, Mountjoy L, Hoeg RT, Dykes KC, Logan AC, Kumaran M, Schwartz MS, Tracy SI, Moore J, Odstrcil Bobillo S, Frey NV, Connor MP, Ladha A, Dholaria B, Sutherland KC, Roloff GW, Muffly LS, Park JH. CAR HEMATOTOX independently predicts outcomes after CD19 CAR-T therapy for acute lymphoblastic leukemia. Blood Adv. 2025 Oct 6:bloodadvances.2025017526. doi: 10.1182/bloodadvances.2025017526. Online ahead of print.
PMID: 41052404DERIVEDCurran KJ, Margossian SP, Kernan NA, Silverman LB, Williams DA, Shukla N, Kobos R, Forlenza CJ, Steinherz P, Prockop S, Boulad F, Spitzer B, Cancio MI, Boelens JJ, Kung AL, Khakoo Y, Szenes V, Park JH, Sauter CS, Heller G, Wang X, Senechal B, O'Reilly RJ, Riviere I, Sadelain M, Brentjens RJ. Toxicity and response after CD19-specific CAR T-cell therapy in pediatric/young adult relapsed/refractory B-ALL. Blood. 2019 Dec 26;134(26):2361-2368. doi: 10.1182/blood.2019001641.
PMID: 31650176DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Kevin Curran, MD
Memorial Sloan Kettering Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 21, 2013
First Posted
May 23, 2013
Study Start
May 1, 2013
Primary Completion
May 1, 2026
Study Completion
May 1, 2026
Last Updated
June 5, 2025
Record last verified: 2025-06