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Trial Title:
Phase Ib/II Study Assessing the Clinical Activity and Safety of Brexucabtagene Autoleucel as a Consolidation in Patients With Relapsed/Refractory (R/R) and Newly Diagnosed B-cell Acute Lymphocytic Leukemia (ALL) Post Cytoreduction With Mini-HCVD-inotuzumab-blinatumomab/HCVAD-inotuzumab-blinatumomab
NCT ID:
NCT06287229
Condition:
Relapsed/Refractory
B-cell Acute Lymphocytic Leukemia
Conditions: Official terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Blinatumomab
Inotuzumab Ozogamicin
Study type:
Interventional
Study phase:
Phase 1/Phase 2
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:
Blinatumomab
Description:
Given by Infusion
Arm group label:
Phase 1B + Phase 2
Intervention type:
Drug
Intervention name:
Inotuzumab Ozogamicin
Description:
Given by IV
Arm group label:
Phase 1B + Phase 2
Intervention type:
Drug
Intervention name:
Hyper-CVAD
Description:
Given by IV Participants younger than 60 years of age, you will receive hyper-CVAD.
Arm group label:
Phase 1B + Phase 2
Intervention type:
Drug
Intervention name:
Mini-hyper-CVD
Description:
Given by IV Participants 60 years of age or older, you will receive mini-hyper-CVD
Arm group label:
Phase 1B + Phase 2
Summary:
To learn about the safety of giving the drug brexucabtagene autoleucel to participants
with relapsed/refractory B-cell ALL after treatment with inotuzumab ozogamicin,
blinatumomab, and either hyper-CVAD or mini-hyper-CVD. Also, to learn if giving
brexucabtagene autoleucel to patients with relapsed/refractory or high-risk, newly
diagnosed B-cell ALL after treatment with inotuzumab ozogamicin, blinatumomab, and either
hyper-CVAD or mini-hyper-CVD can help to control the disease.
Detailed description:
Primary Objectives:
To assess the Efficacy of Brexucabtagene autoleucel [anti-CD19 autologous derived
chimeric antigen receptor T-cell (CAR-T)] in terms of EFS in patients with R/R and
high-risk newly diagnosed B-cell acute lymphoblastic leukemia (B-cell ALL) post
cytoreduction with
mini-hyper-CVD-inotuzumab-blinatumomab/Hyper-CVAD-inotuzumab-blinatumomab
The EFS will be estimated in terms of median EFS and 9-month EFS for the R/R cohort and
18-month EFS for the frontline cohort.
Secondary Objectives:
1. 12 and 24-months overall survival (OS): 12 months for the R/R cohort and 24 months
for the frontline cohort
2. Duration of persistent MRD negativity by flow cytometry and NGS at 9 and 18 months:
9 months for the R/R cohort and 18 months for the frontline cohort
3. Best Ooverall response rates [complete remission (CR) and CR with incomplete count
recovery (CRi)]
4. Achievement of MRD negativity amongst patients in CR and not MRD negative before
Brexucabtagene autoleucel infusion
5. Safety
Exploratory Objectives:
1. CAR-T-cell expansion ((Days 1, 4, 8, 11, 14, 21, 28, monthly up to 3 months and then
every 3 months up to 24 months post infusion)
2. B-cell aplasia (Days 0, 7, 14, 28, monthly up to 3 months and then every 3 months up
to 24 months post infusion)
3. Measurable residual disease (MRD) negativity by next-generation sequencing (NGS) (at
1 in 105-6 sensitivity) (PB on D14 and PB/BM: Day 28, and then Q3 months up to 24
months post infusion)
4. Cytokine panel (Days 0, 1, 2, 4, 7, 10, 14, 28)
5. Additional correlatives samples to address tumor samples and immune system factors
will be collected at baseline, D28 and Q3 months. These include samples for bulk RNA
sequencing of the tumor and germline and single cell RNA sequencing of CAR T-cells
as also for assessing the methylation signatures of the CAR T-cells.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Participants of age ≥18 years with documented relapsed or refractory B-cell ALL
- In the newly diagnosed cohort: Participants of age ≥18 years with high-risk newly
diagnosed B-cell ALL defined as:
1. KMT2A rearranged ALL
2. Complex cytogenetics as per NCCN 2022
3. Low-hypodiploidy/tetraploidy
4. Philadelphia-like ALL (based on CRLF2 overexpression or recurrent Ph-like
genetic fusions)
- Performance status of 0, 1, or 2
- Adequate organ function with creatinine less than or equal to 1.6 mg/dl, bilirubin
less than or equal to 3.5 mg and ALT and AST less than or equal to 5 times
institutional upper limit of normal
- Participants should be CD19 expression positive (>50%) before enrollment
- Participants with chronic viral infections like Hepatitis B-virus, Hepatitis C virus
or Human Immunodeficiency virus I/II will be eligible if they are on therapy and
infections are under control.
Exclusion Criteria
- Philadelphia positive B-cell ALL
- Pregnant or lactating; women of child-bearing potential (WOCBP) must have negative
pregnancy test. WOCBP defined as not post-menopausal for 12 months or no previous
surgical sterilization
- Prior exposure to brexu-cel or other anti-CD-19 CAR T cell therapy
- Active and uncontrolled disease/infection as judged by the treating physician
- Unable or unwilling to sign the consent form
- No other investigational therapy within the past 14 days
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Elias Jabbour, MD
Phone:
713-792-4764
Email:
ejabbour@mdanderson.org
Investigator:
Last name:
Elias Jabbour, MD
Email:
Principal Investigator
Start date:
July 11, 2024
Completion date:
December 31, 2030
Lead sponsor:
Agency:
M.D. Anderson Cancer Center
Agency class:
Other
Source:
M.D. Anderson Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06287229
http://www.mdanderson.org