Precursor B Cell Acute Lymphoblastic Leukemia (B-ALL) Tre... | NCT01044069

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Pts with B Cell Acute Lymphoblastic Leukemia	Experimental	This is a phase I study. Patients with CD19+ ALL (CR, relapsed, MRD, or refractory) are eligible for enrollment. B-ALL patients in first CR will be enrolled but only treated if they develop MRD or a frank relapse, while patients with MRD or with documented relapsed/refractory disease are eligible for immediate treatment. The T cell doses originally proposed in this study were based on doses administered safely in prior autologous T cell adoptive therapy trials but the dose has been modified based on the toxicities observed in patients with morphologic evidence of disease. Patients will be treated with different doses of T cells depending on the amount of disease at the time of T cell infusion. Patients in Cohort 1 (<5% blasts in the BM) will continue to receive 10^6 19-28z+ T cells/kg as previously. Patients in Cohort 2 (≥5% blasts in the BM) will receive the reduced dose of 1x106 19-28z+ T cells/kg).	Biological: gene-modified T cells targeted

Interventions

Name	Type	Description	Arm Group Labels	Other Names
gene-modified T cells targeted	Biological	Pts will undergo leukapheresis. The leukapheresis product will be washed & frozen until the GTF is directed to start T cell production by the PI. CD3+ T cells will be isolated from the leukapheresis, & transduced with the 19-28z chimeric receptor & expanded. All relapsed (either MRD+ or morphologic) & refractory pts get re-induction chemo whenever feasible to optimally reduce the tumor burden prior to the T cell infusion. The re-induction chemo regimen will be selected by the treating dr. based on prior therapy, adverse reactions to chemo & highest likelihood to achieve an optimal response. Once pts recover from the toxicities of the re-induction chemo the disease status will be re-evaluated by repeating bone marrow aspirate or biopsy. Pts get conditioning chemo (min 2 weeks from end of re-induction chemo) followed 2-7 days later by the 19-28z+ T cells. Pts will be tx in 2 cohorts with diff doses of T cells according to the amount of disease immediately prior to the T cell infusion.

Measure	Description	Time Frame
To evaluate the safety of adoptive transfer of gene-modified autologous CD19-specific T cells in adult patients with B-ALL.		2 years

Measure	Description	Time Frame
To assess the anti-leukemic effect of adoptively transferred anti-CD19 T cells.		2 years

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Adult patients are eligible (> or = to 18 year old).
Patients must have B- ALL refractory, relapsed, MRD, or in first CR as described below.
Complete remission is defined as restoration of normal hematopoiesis with a neutrophil count > 1,000 x 106/L, a platelet count > 100,000 x 106/L, and hemoglobin > 10 g/dL. Blasts should be < 5% in a post-treatment bone marrow differential. Furthermore, there should be no clinical evidence of leukemia for a minimum of four weeks.
MRD is defined as patients meeting the criteria for CR above, but with residual disease measured by a quantitative PCR, or by flow or by deep-sequencing of the IgH rearrangements . The assay from blood and/or bone marrow defines MRD by qPCR as a cycle threshold (CT) that is at least 1 CT value < than the lowest CT value from the background. Outside laboratory tests may suffice for this assessment at the discretion of the Principal Investigator.

Relapsed B-ALL will be defined as patients that meet the above criteria for a CR before developing recurrent disease (increased bone marrow blasts). Refractory patients will be defined as patients that have not achieved a CR after 1 cycle of induction chemotherapy

Patients must have a diagnosis of B-ALL by flow cytometry, or bone marrow histology, and/or cytogenetics.
Patients must have CD19+ ALL as confirmed by flow cytometry and/or immunohistochemistry.
Creatinine < 2.0 mg/100 ml, bilirubin < 2.0 mg/100 ml, AST and ALT < 3x normal, PT and PTT < 2x normal outside the setting of stable chronic anticoagulation therapy. LFTs (Bilirubin, AST, and/or ALT) may be acceptable if the elevation is secondary to leukemia infiltration or leukemia therapy with tyrosine kinase inhibitors.
Adequate cardiac function (LVEF ≥ 40%) as assessed by ECHO or MUGA or other similar cardiac imaging performed within 1 month of enrollment.
Adequate pulmonary function as assessed by ≥ 92% oxygen saturation on room air by pulse oximetry.
Patients must have adequate access for leukapheresis procedure as assessed by staff from the MSKCC Donor Room.
Life expectancy > 3 months

Exclusion Criteria:

Karnofsky performance status < 70.
Active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF) or symptomatic CNS leukemia (i.e. cranial nerve palsies or other significant neurologic dysfunction) within 28 days of enrollment. Prophylactic intrathecal medication is not a reason for exclusion.
Patients previously treated with an allogeneic SCT that is currently complicated by active GVHD requiring T cell suppressive therapy.

Patients with following cardiac conditions will be excluded:

New York Heart Association (NYHA) stage III or IV congestive heart failure
Myocardial infarction ≤6 months prior to enrollment
History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration
History of severe non-ischemic cardiomyopathy with EF ≤20%
- Patients with HIV, hepatitis B or hepatitis C infection.
- Patients with any concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation.

Name	Affiliation	Role
Jae Park, MD	Memorial Sloan Kettering Cancer Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Memorial Sloan Kettering Cancer Center		New York	New York	10065	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
41052404	Derived	Valtis YK, Lin C, Nemirovsky D, Devlin S, Rejeski K, Curran KJ, Wang X, Shah NN, Jeyakumar N, Miller K, Zhang A, Kota VK, Al Darobi AH, Muhsen I, Sasine J, Aldoss I, Advani AS, Reshef R, Chen EC, Kopmar N, Tsai SB, Hilal T, Shah BD, Faramand R, Solh MM, Tan V, Bezerra E, Battiwalla M, Ramakrishnan A, Mathews J, Shaughnessy P, Mountjoy L, Hoeg RT, Dykes KC, Logan AC, Kumaran MV, Schwartz M, Tracy S, Moore J, Odstrcil Bobillo S, Frey NV, Connor M, Ladha A, Dholaria B, Sutherland K, Roloff GW, Muffly LS, Park JH. CAR HEMATOTOX independently predicts outcomes after CD19 CAR-T therapy for acute lymphoblastic leukemia. Blood Adv. 2026 Jan 13;10(1):276-288. doi: 10.1182/bloodadvances.2025017526.
32780846

ID	Term
D007938	Leukemia
D054198	Precursor Cell Lymphoblastic Leukemia-Lymphoma

ID	Term
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D007945	Leukemia, Lymphoid
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases