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Trial Title:
Autologous CD22 CAR T Cells Following Commercial CD19 CAR T Cells in B Cell Malignancies
NCT ID:
NCT06408194
Condition:
Leukemia
Acute Lymphoblastic Leukemia
Conditions: Official terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Tisagenlecleucel
Conditions: Keywords:
KYMRIAH
CAR T
Tisagenlecleucel
Lymphodepletion
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
CD22CART infusion
Description:
CD22CART will be administered after Standard of Care (SOC) administration of
tisagenlecleucel.
Arm group label:
Lymphodepletion
Intervention type:
Drug
Intervention name:
Tisagenlecleucel
Description:
All enrolled participants will receive lymphodepletion followed by standard of care
tisagenlecleucel infusion.
Arm group label:
Lymphodepletion
Other name:
KYMRIAH
Summary:
The primary purpose of this study is to determine safety, feasibility, and the Maximum
Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of CD22 Chimeric Antigen Receptor
T-Cell Therapy (CART) cells when administered 28 to 42 days after an infusion of a
commercial CAR called Tisagenlecleucel, to children and young adults with relapsed or
refractory B-cell leukemia.
Detailed description:
Primary Objectives:
Phase 1 portion (Safety lead-in):
Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) dose of
CD22CART in children and young adults with R/R CD19 and CD22 expressing B-cell
malignancies administered after infusion of tisagenlecleucel according to FDA approved
dose range.
Phase 1b portion (Expansion cohort) Establish the feasibility of delivering CD22CART
following infusion of commercial tisagenlecleucel, administered per FDA approved Package
Insert, in children and young adults with B cell malignancies.
Determine the safety of administering the RP2D of CD22CART 28 to 42 days after infusion
of FDA approved commercial tisagenlecleucel in children and young adults with B cell
malignancies.
Secondary Objectives:
1. Describe the clinical activity of serial infusion of tisagenlecleucel followed by
CD22CART in children and young adults with R/R B-cell malignancies.
2. Assess the rate of ongoing B cell aplasia at 6 months after initial tisagenlecleucel
infusion, when tisagenlecleucel is followed by serial CD22CART infusion within 42
days.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Diagnosis of histologically confirmed relapsed/refractory (R/R) B cell acute
lymphoblastic leukemia (ALL)
2. Must be eligible to receive commercial KYMRIAH® (tisagenlecleucel) according to FDA
approved package insert (refractory disease or in second or later relapse)
3. CD19 and CD22 expression must be demonstrated on malignant cells by
immunohistochemistry or flow cytometry. CD19 and CD22 expression at any level of
expression will be acceptable, as that is the standard for commercial KYMRIAH®
(tisagenlecleucel) and the optimal level of CD22 expression is not well defined.
4. Age: ≥ 1 year of age and ≤ 25 years and 364 days of age at time of enrollment.
5. Performance Status: Participants > 16 years of age: Karnofsky ≥ 50%; Participants ≤
16 years of age: Lansky scale ≥ 50%.
6. Normal Organ and Marrow Function
- Absolute Neutrophil Count (ANC) ≥ 750/uL*
- Platelet count ≥ 50,000/uL*
- Absolute Lymphocyte Count ALC > 150/uL*
- Adequate renal, hepatic, pulmonary and cardiac function defined as:
- Baseline oxygen saturation > 92% on room air
- Creatinine within ULN for age or Creatinine clearance (as estimated by
Cockcroft Gault Equation) ≥ 60 mL/min
- Total bilirubin ≤ 1.5 mg/dl, except in Participants with Gilbert's
syndrome. [Elevations related to leukemia involvement of the liver will
not disqualify a subject]
- Alanine Transaminase (ALT) or Aspartate Aminotransferase (AST) ≤ 10 x ULN
(except in Participants with liver involvement by leukemia)
- Cardiac ejection fraction ≥ 40%, no evidence of pericardial effusion as
determined by an Echocardiogram.
- if these cytopenias are not judged by the investigator to be due to
underlying disease (i.e. potentially reversible with anti-neoplastic
therapy); A subject will not be excluded because of pancytopenia ≥ Grade 3
if it is due to disease, based on the results of bone marrow studies.
7. Participants with Central Nervous System (CNS) involvement or a history of CNS
involvement are eligible only in the absence of neurologic symptoms that may mask or
interfere with neurological assessment of toxicity
8. Participants who have undergone autologous SCT with disease progression or relapse
following SCT are eligible. Participants with history of allogeneic SCT must be at
least 100 days from SCT, have no evidence of Graft versus Host Disease (GvHD), and
no longer taking immunosuppressive agents for at least 30 days prior to enrollment.
9. Females of child bearing potential and males of child fathering potential must be
willing to practice birth control during and for 4 months post chemotherapy or for
as long as Chimeric Antigen Receptor (CAR) T cells are detectable in peripheral
blood.
10. Females of child bearing potential must have negative pregnancy test.
11. Must meet wash out period since prior therapies according to commercial KYMRIAH®
(tisagenlecleucel) SOPs.
12. Must have recovered from acute side effects from prior therapy to meet eligibility.
13. If had prior CAR therapy, will be eligible if at least 30 days has elapsed prior to
apheresis.
14. Ability to give informed consent. All Participants ≥ 18 years of age must be able to
give informed consent. For participants <18 years old their legal authorized
representative (LAR) (i.e. parent or guardian) must give informed consent. Pediatric
participants will be included in age appropriate discussion and assent per
institutional SOPs will be obtained for those > 7 years of age, when appropriate. If
a minor becomes of age during participation of this study, he/she will be asked to
reconsent as an adult.
- A subject will not be excluded because of pancytopenia ≥ Grade 3 if it is felt
by the investigator to be due to underlying disease.
Exclusion Criteria:
1. May not have Human Immunodeficiency Virus (HIV)/Hepatitis B (HBV) or Hepatitis C
(HCV infection) or uncontrolled, symptomatic, intercurrent illness.
2. May not have hyperleukocytosis (≥ 50,000 blasts/μL) or rapidly progressive disease
that in the estimation of the investigator and sponsor would compromise ability to
complete study therapy.
3. May not have severe, immediate hypersensitivity reaction attributed to compounds of
similar chemical or biologic composition to any agents used in study.
4. May not have active CNS disorder, or history of MI, cardiac angioplasty or stenting,
unstable angina or other clinically significant cardiac disease with 12 months of
enrollment.
5. May not have primary immunodeficiency or history of autoimmune disease (e.g. Crohns,
rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression/systemic
disease modifying agents within the last 2 years.
Gender:
All
Minimum age:
1 Year
Maximum age:
25 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Stanford University
Address:
City:
Palo Alto
Zip:
94304
Country:
United States
Status:
Recruiting
Contact:
Last name:
Michelle Fujimoto
Phone:
650-736-0539
Email:
mfujimot@stanford.edu
Investigator:
Last name:
Kara L Davis, DO
Email:
Principal Investigator
Start date:
May 13, 2024
Completion date:
June 2025
Lead sponsor:
Agency:
Stanford University
Agency class:
Other
Source:
Stanford University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06408194