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Purpose

This study is a phase I study designed to evaluate the safety of CD19-CD22-CAR T cells. Primary Objective: To determine the safety profile and propose the recommended phase 2 dose (RP2D) of autologous CD19-CD22-CAR T cells in patients ≤ 21 years of age with recurrent/refractory CD19- and/or CD22-positive leukemia. Secondary Objective: To evaluate the anti-leukemic activity of CD19-CD22-CAR T cells.

Conditions

Eligibility

Eligible Ages
Under 21 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Age <21 years old - Relapsed/refractory CD19- and/or CD22-positive acute leukemia defined as: *CD19 and/or CD22-positivity confirmed within 2 months and after receipt of any CD19 or CD22-directed therapy - Second or greater relapse - Any relapse after allogeneic HCT - Refractory disease (primary or in relapse) despite therapy designed to induce remission - Estimated life expectancy of > 12 weeks - Karnofsky or Lansky (age-dependent) performance score ≥50 (Appendix A) - For females of childbearing age: - Not lactating with intent to breastfeed - Not pregnant with negative serum or urine pregnancy test within 7 days prior to enrollment

Exclusion Criteria

  • Known primary immunodeficiency - Known HIV positivity - Known contraindication to receiving protocol defined lymphodepleting - chemotherapy regimen - History of hypersensitivity reaction to murine protein-containing products Treatment Eligibility Inclusion Criteria: - Age < 21 years old - Detectable disease in the bone marrow - Estimated life expectancy of > 8 weeks - Karnofsky or Lansky (age-dependent) performance score > 50 (Appendix A) - Adequate cardiac function defined as left ventricular ejection fraction >40%, or shortening fraction > 25% - EKG without evidence of clinically significant arrhythmia - Adequate renal function defined as creatinine clearance or radioisotope GFR >50 mL/min/1.73m2 (GFR >40 mL/min/1.73m2 if <2 years of age) - Adequate pulmonary function defined as forced vital capacity (FVC) >50% of predicted value; or pulse oximetry >92% on room air - Total bilirubin < 3 times the upper limit of normal for age, except in subjects with Gilbert's syndrome - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 5 times the upper limit of normal for age - Has recovered from all NCI CTAE grade III-IV, non-hematologic acute toxicities from prior therapy - Prior to planned CAR T cell infusion, patients with a history of prior allogeneicHCT must be at least 3 months from HCT, have no evidence of acute GVHD, and have not received a donor lymphocyte infusion (DLI) within the 28 daysprior to planned infusion - For females of childbearing age: - Not lactating with intent to breastfeed - Not pregnant with negative serum or urine pregnancy test within 7 days prior to enrollment - If sexually active, agreement to use birth control until 3 months after T cell infusion. Male partners should use a condom. Exclusion Criteria: - Known primary immunodeficiency - Known HIV positivity - Known contraindication to receiving protocol defined lymphodepleting - chemotherapy regimen - History of hypersensitivity reactions to murine protein-containing products - Severe, uncontrolled bacterial, viral or fungal infection - Active CNS-3 disease - Evidence of active, uncontrolled neurologic disease

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
CD19-CD22-CAR T cell therapy 		This study has two parts: Collection and Manufacturing Phase - Patients will have white blood cells collected in the St. Jude Blood Donor Center through a procedure called apheresis, or your doctors may use a previously collected frozen product. The collected cells will be engineered to improve their ability to recognize and kill cancer cells. The final cell product is referred to as the CD19-CD22 CAR T cells. Treatment Phase - Eligible patients will receive chemotherapy before receiving the CAR T cells.
  • Drug: Fludarabine
    IV
  • Drug: Cyclophosphamide
    IV
  • Drug: Mesna
    IV
  • Device: CD19-CD22 CAR T cell infusion
    CAR T cell infusion will be given intravenously, either centrally or peripherally.

Recruiting Locations

St. Jude Children's Research Hospital
Memphis 4641239, Tennessee 4662168 38105
Contact:
Rebecca Epperly, MD
866-278-5833
referralinfo@stjude.org

More Details

Status
Recruiting
Sponsor
St. Jude Children's Research Hospital

Study Contact

Rebecca Epperly, MD
8662785833
referralinfo@stjude.org

Detailed Description

Treatment will include a single course of lymphodepleting chemotherapy (fludarabine/cyclophosphamide) followed by CAR T cell infusion. CAR T cell dose will be determined by the protocol-defined dose escalation scheme, based on the number of CAR+ T cells and participant weight.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.