Trial Title:
CD19-Car T Cell Therapy for the Treatment of Older Adults With Acute Lymphoblastic Leukemia in First Remission
NCT ID:
NCT05707273
Condition:
B Acute Lymphoblastic Leukemia
Conditions: Official terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Cyclophosphamide
Fludarabine
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:
Autologous Anti-CD19 CAR-expressing T Lymphocytes
Description:
Given IV
Arm group label:
Treatment (CD19-CAR T cells)
Other name:
Autologous Anti-CD19-CAR T Cells
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (CD19-CAR T cells)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Marrow Aspiration and Biopsy
Description:
Undergo bone marrow aspirate
Arm group label:
Treatment (CD19-CAR T cells)
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Given IV
Arm group label:
Treatment (CD19-CAR T cells)
Other name:
(-)-Cyclophosphamide
Other name:
2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
Other name:
Carloxan
Other name:
Ciclofosfamida
Other name:
Ciclofosfamide
Other name:
Cicloxal
Other name:
Clafen
Other name:
Claphene
Other name:
CP monohydrate
Other name:
CTX
Other name:
CYCLO-cell
Other name:
Cycloblastin
Other name:
Cycloblastine
Other name:
Cyclophospham
Other name:
Cyclophosphamid monohydrate
Other name:
Cyclophosphamide Monohydrate
Other name:
Cyclophosphamidum
Other name:
Cyclophosphan
Other name:
Cyclophosphane
Other name:
Cyclophosphanum
Other name:
Cyclostin
Other name:
Cyclostine
Other name:
Cytophosphan
Other name:
Cytophosphane
Other name:
Cytoxan
Other name:
Fosfaseron
Other name:
Genoxal
Other name:
Genuxal
Other name:
Ledoxina
Other name:
Mitoxan
Other name:
Neosar
Other name:
Revimmune
Other name:
Syklofosfamid
Other name:
WR- 138719
Intervention type:
Drug
Intervention name:
Fludarabine
Description:
Given IV
Arm group label:
Treatment (CD19-CAR T cells)
Other name:
Fluradosa
Intervention type:
Procedure
Intervention name:
Leukapheresis
Description:
Undergo T-cell leukapheresis
Arm group label:
Treatment (CD19-CAR T cells)
Other name:
Leukocytopheresis
Other name:
Therapeutic Leukopheresis
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Complete questionnaires
Arm group label:
Treatment (CD19-CAR T cells)
Summary:
This phase I trial tests the safety, side effects, and best dose of autologous anti-CD19
CAR-expressing T lymphocytes (CD19-CAR T cells) in older adults with B-cell acute
lymphoblastic leukemia. Chimeric antigen receptor (CAR) T-cell therapy is a type of
treatment in which a patient's T cells (a type of immune system cell) are changed in the
laboratory so they will attack cancer cells. T cells are taken from a patient's blood.
Then the gene for a special receptor that binds to a certain protein on the patient's
cancer cells is added to the T cells in the laboratory. The special receptor is called a
chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the
laboratory and given to the patient by infusion for treatment of B-cell acute
lymphoblastic leukemia.
Detailed description:
PRIMARY OBJECTIVE:
I. Assess the safety and tolerability of autologous CD19-CAR T cell therapy by evaluation
of toxicities including type, frequency, severity, attribution, time course and duration
in older patients with B-cell acute lymphoblastic leukemia (ALL) in first morphological
complete remission (CR1).
SECONDARY OBJECTIVES:
I. Assess the feasibility of manufacturing and infusing CD19-CAR T cells in older adults
with B-cell ALL in CR1.
II. Evaluate the rate of MRD- remission in patients who had MRD+ disease at the time of
infusion.
III. Evaluate the overall risk of relapse. IV. Evaluate the risk of central nervous
system (CNS) relapse (isolated and combined with bone marrow relapse).
V. Estimate the 1-year event-free survival (EFS) rate post CD19-CAR T cell therapy.
VI. Estimate 1-year overall survival (OS) post CD19-CAR T cell therapy. VII. Describe
development of frailty after CD19-CAR T cell therapy.
EXPLORATORY OBJECTIVES:
I. Measure expansion and persistence of CD19-CAR T cells in peripheral blood (PB), bone
marrow (BM) and cerebrospinal fluid (CSF).
II. Assess the duration of B-cell aplasia. III. Describe cytokine levels in PB over the
study period.
OUTLINE: This is a dose-escalation study of CD19-CAR T cell therapy followed by a
dose-expansion study.
Patients undergo T cell leukapheresis, receive fludarabine and cyclophosphamide
intravenously (IV), and then receive CD19-CAR T cell infusion IV on study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Documented informed consent of the participant
- Agreement to allow the use of archival tissue from diagnostic tumor biopsies
- If unavailable, exceptions may be granted with Study Principal Investigator
(PI) approval
- Note: For research participants who do not speak English, a short form consent
may be used with a City of Hope (COH) certified interpreter/translator to
proceed with screening and leukapheresis, while the request for a translated
full consent is processed. However, the research participant is allowed to
proceed with lymphodepletion and T cell infusion only after the translated full
consent form is signed
- Age: >= 55 years
- Eastern Cooperative Oncology Group (ECOG) < 2 / Karnofsky Performance Status (KPS)
>= 70
- Ability to read and understand English for Questionnaires
- Histologically confirmed CD19+ ALL at the time of diagnosis
- In morphological first complete remission regardless of minimal residual disease
(MRD) status
- No immediate plan for transplant
- Remission after induction +/- reinduction therapy
- Fully recovered from the acute toxic effects (except alopecia) to =< Grade 1 to
prior anti-cancer therapy
- Total bilirubin =< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease)
- Aspartate aminotransferase (AST) =< 3 x ULN
- Alanine transaminase (ALT) =< 3 x ULN
- Creatinine clearance of >= 60 mL/min per 24 hour urine test or the Cockcroft-Gault
formula
- Left ventricular ejection fraction (LVEF) >= 50%
- Note: To be performed within 28 days prior to start of protocol therapy
- Oxygen (O2) saturation > 92% on room air.
- Note: To be performed within 28 days prior to start of protocol therapy
- Seronegative for human immunodeficiency virus (HIV) (quantitative polymerase chain
reaction [qPCR]), hepatitis C virus (HCV), active hepatitis B virus (HBV) (Surface
Antigen Negative), and syphilis (rapid plasma reagin [RPR])
- If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed
OR
- If seropositive for HIV, HCV or HBV, nucleic acid quantitation must be
performed. Viral load must be undetectable
- Meets other institutional and federal requirements for infectious disease titer
requirements
- Note Infectious disease testing to be performed within 28 days prior to start
of protocol therapy
- Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
- If the urine test is positive or cannot be confirmed as negative, a serum
pregnancy test will be required
- Agreement by females and males of childbearing potential* to use an effective method
of birth control or abstain from heterosexual activity for the course of the study
through at least 6 months after the last dose of protocol therapy.
- Childbearing potential defined as not being surgically sterilized (men and
women) or have not been free from menses for > 1 year (women only)
Exclusion Criteria:
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to study agent(s)
- Research participant with known CNS-2 or CNS-3 involvement that is refractory to
intrathecal chemotherapy and/or cranio-spinal radiation. Research participants with
a history of central nervous system (CNS) disease that has been effectively treated
to complete remission (<5 WBC/mm3 and no blasts in cerebrospinal fluid [CSF]) will
be eligible
- Autoimmune disease or active graft versus host disease (GVHD) requiring systemic
immunosuppressant therapy
- Class III/IV cardiovascular disability according to the New York Heart Association
(NYHA) Classification
- History of other malignancies, except for malignancy surgically resected (or treated
with other modalities) with curative intent, basal cell carcinoma of the skin or
localized squamous cell carcinoma of the skin; non-muscle invasive bladder cancer;
malignancy treated with curative intent with no known active disease present for >=
2 years
- Clinically significant uncontrolled illness
- Active systemic uncontrolled infection requiring antibiotics
- Known history of HIV or hepatitis B or hepatitis C infection
- Subjects who are hepatitis B core antibody (anti-HBc) positive and who are
surface antigen negative will need to have a negative polymerase chain reaction
(PCR) result. Those who are hepatitis B surface antigen (HbsAg) positive or
hepatitis B PCR positive will be excluded
- Subjects who are hepatitis B core antibody positive (or have a known
history of HBV infection) should be monitored quarterly with a
quantitative PCR test for HBV deoxyribonucleic acid (DNA). HBV monitoring
should last until 12 months after last dose of study drug. Any subject
with a rising viral load (above lower limit of detection) should
discontinue study drug and have antiviral therapy instituted and a
consultation with a physician with expertise in managing hepatitis B.
Subjects who are core Ab positive at study enrollment are strongly
recommended to start Entecavir before start and until completion of study
treatment
- Subjects who are hepatitis C antibody positive will need to have a
negative PCR result. Those who are hepatitis C PCR positive will be
excluded
- Females only: Pregnant or breastfeeding
- Concurrent use of systemic steroids or chronic use of immunosuppressant medications.
Recent or current use of inhaled steroids is not exclusionary. Physiologic
replacement of steroids (prednisone =< 7.5 mg /day or equivalent) is allowed
- Any other condition that would, in the Investigator's judgment, contraindicate the
patient's participation in the clinical study due to safety concerns with clinical
study procedures
- Prospective participants who, in the opinion of the investigator, may not be able to
comply with all study procedures (including compliance issues related to
feasibility/logistics)
Gender:
All
Minimum age:
55 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope Medical Center
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ibrahim Aldoss
Phone:
626-218-2405
Email:
ialdoss@coh.org
Investigator:
Last name:
Ibrahim Aldoss
Email:
Principal Investigator
Start date:
April 26, 2023
Completion date:
July 24, 2026
Lead sponsor:
Agency:
City of Hope Medical Center
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
City of Hope Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05707273
