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Trial Title:
A Study of Fully Human BCMA Chimeric Antigen Receptor Autologous T Cell Injection (CT103A) in the Treatment of Patients With Relapsed/Refractory Multiple Myeloma
NCT ID:
NCT05698303
Condition:
Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Conditions: Keywords:
relapsed/refractory multiple myeloma
RRMM
CAR-T
BCMA
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Fully human BCMA chimeric antigen receptor autologous T cell injection (CT103A)
Description:
CT103A is an BCMA targeted genetically modified autologous T cell immunotherapy product
that identifies and eliminates BCMA-expressing malignant and normal cells. CAR
specifically recognizes BCMA with a low-immunogenic fully human single chain fragment
variable (scFv), promotes CAR-T activation, proliferation, cytokine secretion and target
cell killing through the CD3ζ domain, and enhances CAR-T proliferation and persistence
through co-stimulatory signaling via 4-1BB.
Arm group label:
CT103A in patients with RRMM
Other name:
CT103A
Summary:
It is a dose expansion, open-label, phase Ib study to evaluate the safety, efficacy,
pharmacokinetic (PK), pharmacodynamic (PD), and immunogenicity of CT103A in patients with
relapsed/refractory multiple myeloma.
Detailed description:
A total of at least 12 subjects are planned to be enrolled in this study. Each subject
will proceed through the following study periods:
- Screening
- Leukapheresis
- Bridging therapy (at the discretion of the investigator)
- Pre-lymphodepletion assessment
- Lymphodepleting chemotherapy
- Pre-infusion Assessment
- CT103A infusion (Day 0)
- 28-Day safety evaluation period
- Post-treatment follow-up period (Day 29 through year 2)
All the subjects will be followed for safety and efficacy until disease progression,
initiation of subsequent anti-myeloma therapy, withdrawal, death, loss to follow-up,
study completion, end of study, or study termination, whichever occurs first. Subjects
except those that are deceased, lost to follow-up, or have withdrawn their ICF will enter
the long-term follow-up (LTFU) under a separate protocol for at least 15 years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. ≥ 18 years of age.
2. Documented diagnosed with multiple myeloma according to the IMWG diagnostic
criteria.
3. Have received at least 3 prior lines of therapy, including a proteasome inhibitor,
an immunomodulator-based chemotherapy, and an anti-CD38 therapy (prior exposure can
be from different monotherapy or combination regimens), or are refractory to both a
proteasome inhibitor and an immunomodulatory agent (i.e., double refractory).
4. Documented disease progression during or within 12 months of the most recent
anti-myeloma treatment (except for subjects who received CAR-T as last-line
therapy).
5. For subjects with previous BCMA-targeted therapy, the best response should be at
least PR, and positive BCMA expression on tumor cells by immunohistochemistry (IHC)
or flow cytometry is required before enrollment.
6. The presence of measurable lesion according to IMWG 2016 criteria at screening as
determined by any of the following criteria:
- Serum M-protein level ≥1.0 g/dL or urine M protein level ≥ 200 mg/24 h; or
- Light chain multiple myeloma without measurable lesions in serum or urine:
Involved serum free light chain ≥ 10 mg/dL and abnormal serum κ/λ free light
chain ratio.
7. ECOG score of 0 or 1 (refer to Appendix 2)
8. Subjects must have appropriate organ function and meet all the following laboratory
test results prior to enrollment:
- Hematology: Absolute neutrophil count (ANC) ≥ 1×109/L (supportive growth factor
is permitted, but must be without supportive treatment within 7 days before the
laboratory test); absolute lymphocyte count (ALC) ≥0.3×109/L; platelet count
≥50×109/L (must be without supportive blood transfusion within 7 days before
the laboratory test); hemoglobin ≥80 g/L (without transfusion of red blood
cells [RBC] within 7 days before the laboratory test; the use of recombinant
human erythropoietin is permitted).
- Liver function: Alanine transaminase (ALT) and aspartate transaminase (AST) ≤
2.5×upper limit of normal (ULN); serum total bilirubin ≤ 1.5×ULN except with
known Gilbert's syndrome who have serum bilirubin ≤ 3×ULN.
- Renal function: Creatinine clearance (CrCl) calculated using the
Cockcroft-Gault formula ≥ 40 ml/min.
- Coagulation function: Fibrinogen ≥1.0 g/L; activated partial thromboplastin
time ≤1.5× ULN, prothrombin time (PT) ≤1.5× ULN.
- Corrected serum calcium ≤11 mg/dL
- Oxygen saturation (by Fingertip Pulse Oximeter) ≥92%.
- Left ventricular ejection fraction (LVEF) ≥45%.
9. Female subjects of childbearing potential or male subjects with a partner of
childbearing potential agree to use effective contraception methods from screening
and continued during study treatment until one year after the last dose.
10. The subject must personally sign an informed consent form approved by the ethics
committee in writing.
Exclusion Criteria:
1. Subjects with graft versus host disease (GVHD) or those requiring long-term use of
immunosuppressants.
2. Received autologous hematopoietic stem cell transplant (Auto-HSCT) within 12 weeks
before apheresis or received prior allogeneic hematopoietic stem cell transplant
(Allo-HSCT).
3. Received prior anti-myeloma therapies as follows:
- Treatment with monoclonal antibodies within 21 days prior to apheresis, or
- Treatment with cytotoxic chemotherapy or proteasome inhibitor within 14 days
prior to apheresis, or
- Treatment with immunomodulator within 7 days prior to apheresis, or
- Anti-myeloma therapies other than those described above within 14 days or at
least 5 half-lives (whichever is shorter) prior to apheresis.
4. Use of glucocorticoids (defined as prednisone or equivalent > 20 mg/day) at a
therapeutic dose within 7 days prior to apheresis. Physiologic replacement, topical,
and inhalation steroids are permitted, nevertheless.
5. Severe heart disease: Including but not limited to unstable angina, myocardial
infarction (within 6 months prior to screening), congestive cardiac failure (New
York Heart Association [NYHA] classification grade ≥ III), severe arrhythmia.
6. Unstable systemic diseases judged by the investigator: Including but not limited to
severe liver, kidney or metabolic diseases requiring therapy.
7. Malignancies other than multiple myeloma within 5 years prior to screening,
excluding adequately treated carcinoma in situ of cervix, basal or squamous
epithelial cell skin cancer, localized prostate cancer post radical operation,
ductal carcinoma in situ of the breast post radical operation.
8. History of organ transplant.
9. Suspected or confirmed central nervous system involvement.
10. Plasma cell leukemia at the time of screening (>2.0×109/L plasma cells by standard
differential), Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy,
organomegaly, endocrinopathy, monoclonal protein, and skin changes), or primary AL
amyloidosis.
11. Major surgery within 2 weeks prior to apheresis, or planned surgery within 2 weeks
after study treatment administration (subjects who plan to receive surgery under
local anesthesia are permitted to be enrolled in this study).
12. Treated with other interventional clinical investigational products within 1 month
before signing the informed consent form (ICF).
13. Evidence of serious active viral, bacterial, or uncontrolled systemic fungal
infection prior to apheresis.
14. Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb)
with detectable hepatitis B virus (HBV) DNA in peripheral blood; positive hepatitis
C virus (HCV) antibody with positive HCV RNA in peripheral blood; positive human
immunodeficiency virus (HIV) antibody; positive cytomegalovirus (CMV) DNA; positive
syphilis test.
15. Pregnant or breastfeeding women or planning to become pregnant while enrolled in
this study or within 1 year after receiving study treatment.
16. Stroke, seizure or psychosis within 6 months of signing ICF.
17. Non-hematological toxicities from previous anti-myeloma therapy have not recovered
to baseline or grade ≤1 (NCI-CTCAE v5.0, except for alopecia and grade 2 peripheral
neuropathy).
18. Any issue that would impair the ability of the subject to receive or tolerate the
planned treatment, to understand informed consent or any condition for which, in the
opinion of the investigator, participation would not be in the best interest of the
subject (e.g., compromise the well-being) or that could prevent, limit, or confound
the protocol-specified assessments.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
The University of Texas MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Contact:
Last name:
Robert Z. Orlowski, M.D., Ph.D.
Phone:
713-792-2860
Email:
rorlowsk@mdanderson.org
Start date:
May 8, 2023
Completion date:
January 15, 2026
Lead sponsor:
Agency:
Nanjing IASO Biotechnology Co., Ltd.
Agency class:
Industry
Source:
Nanjing IASO Biotechnology Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05698303