Trial Title:
CD70 Targeted CAR-T Cells in CD70 Positive Relapsed/Refractory Lymphoma
NCT ID:
NCT05948033
Condition:
Lymphoma
Conditions: Official terms:
Lymphoma
Conditions: Keywords:
CD70
Relapsed/Refractory
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:
Biological
Intervention name:
CD70-targeting CAR-T cells
Description:
Dose escalation:
Dose1 (1×10^6 cells/kg) ,Dose 2(3×10^6 cells/kg) ,Dose 3 (1×10^7 cells/kg)
Doseexpansion: RP2D
Drug: Fludarabine
Intravenous fludarabine 25-30 mg/m^2/day on days 5, -4, and -3.
Drug: Cyclophosphamide
Intravenous cyclophosphamide 300-500 mg/m^2/day on days -5, -4, and -3.
Arm group label:
CD70-targeting CAR-T cells
Summary:
In this single-center, single-arm,prospective, open-label, phase 1/2 study, the safety
and efficacy of autologous CD70 targeted chimeric antigen receptor modified T (CAR-T)
cell therapy will be evaluated in patients with CD70 antigen positive Relapsed/Refractory
Lymphoma . In this clinical trial, at least 12 eligible patients in dose escalation
period will be enrolled to receive 3 doses of CD70-CAR cell therapy according to the
"3+3" principle. In dose expansion period, additional at most 21 eligible patients will
be enrolled to receive CD70-CAR-T cell therapy at dose of recommended phase 2 dose(RP2D).
Detailed description:
CAR-T cell therapy has been identified as a breakthrough therapy in hematologic
malignancies,especially anti-CD19 CAR-T cell therapy in the treatment of r/r B-NHL has
achieved remarkable efficacy.However, relapse with CD19-negative tumor after treatment
with anti-CD19 CAR-T cells has been reported in different types of B-cell lymphoid
malignancies, with a percentage up to 38% in patients with non-Hodgkin lymphoma (NHL).At
present, the CAR-T cell treatment for HL is mainly confined to CD30 antigen,with an
objective response rate (ORR) only 38%~62%. Therefore, a more effective treatment
strategy is needed for these patients.
CD70, the membrane-binding ligand of the CD27 (a tumor necrosis factor receptor
superfamily), has been reported to mediate tumour cell proliferation and be expressed on
the malignant cells of diffuse large B-cell lymphoma (DLBCL)，mantle cell lymphoma (MCL)
and follicular lymphomas (FL), as well as Hodgkin lymphoma, etc,but rarely on normal B
cells or T cells,indicating CD70 targeted treament has emerged as potentialnovel
immunotherapeutic strategy.Preclinical study demonstrated CD70-CAR-T cells represent a
new therapeutic option for the treatment of patients with CD19-negative recurrence of
lymphoma.Based on the preclinical data, we conduct this clinical trial in order to test
the the safety profiles and anti-tumor activities of CD70-CAR-T cells in vivo. In dose
escalation period, at least 12 eligible patients will be enrolled and receive 3 doses of
CD70-CAR-T cell therapy (1 × 10^6 cells/kg, 3 × 10^6 cells/kg, 1 × 10^7 cells/kg)
according to the "3+3" principle. In dose expansion period, additional at most 21
eligible patients will be enrolled to receive CD70-CAR-T cell infusion at dose of RP2D,
which is determined by data from dose escalation period, including occurrence of dose
limiting toxicities(DLT), pharmacokinetics/pharmacodynamics, efficacy and other
parameters, to furtherly evaluate the safety and efficacy profiles of CD70-CAR-T cell
therapy.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Patients eligible for inclusion in this study had to meet all of the following criteria:
1. Age 18-75 (inclusive);
2. ECOG performance status ≤2 and Estimated life expectancy of more than 3 months;
3. Patients with histologically confirmed lymphoma including the following types
defined by the World Health Organization(WHO) 2016:HL,Aggressive B-cell
non-Hodgkin's lymphoma(Diffuse large B-cell lymphoma,High grade B-cell
lymphoma,burkitt's lymphoma,Mantle cell lymph,Anaplastic large cell lymphoma, etc.)
and Indolent lymphoma（Including but not limited to follicular lymphoma, marginal
zone lymphoma, chronic lymphocytic leukemia, etc.）
4. Relapse after treatment with ≥2 lines systemic therapy for all the above disease
types. Relapse disease is defined as disease progression after last regimen.
Refractory disease is defined as no CR tofirst-line therapy:
- PD as best response to first-line therapy, or
- SD as best response after at least 4 cycles of first-line therapy (eg, 4 cycles
of R- CHOP), or
- PR as best response after at least 6 cycles and biopsy-proven residual disease
or disease progression ≤ 6 months of therapy, or
- Refractory post-autologous stem cell transplant (ASCT) i. Disease progression
or relapsed less than or equal to 12 months of ASCT (must have biopsy prove
recurrence in relapsed individuals) ii. If salvage therapy is given post-ASCT,
the individual must have had no response to or relapsed after the last line of
therapy.
- Individuals must have received adequate prior therapy.
5. CD70 antigen expression percentage ≥ 10%.
6. Successful leukapheresis assessment and preculture of T cells;
7. According to Lugano response criteria 2014, there should be at least one evaluable
tumor focus. Evaluable tumor focus was defined as that with the longest diameter of
intranodal focus > 1.5cm, the longest diameter of extranodal focus > 1.0cm assessed
by computed tomography (CT) ormagnetic resonance imaging (MRI).
8. Functions of important organs meet the following requirements:ANC≥≥1×10^9/L;
Platelet count ≥50×10^9/L; Hemoglobin ≥80 g/L;Serum AST and serum ALT, ≤3.0 x ULN
(≤5 x ULN for patients with liver metastases); Total serum bilirubin ≤3.0 x ULN);
Serum creatinine ≤1.5xULN ; Echocardiography showed left ventricular ejection
fraction ≥50%.Pulmonary function: oxygen saturation of blood (SaO2) ≥92% in indoor
air environment.
9. Toxicity from previous antitumor therapy ≤ grade 1 (according to CTCAE version 5.0)
or to an acceptable level of inclusion/exclusion criteria (other toxicities such as
alopecia and vitiligo considered by the investigator to pose no safety risk to the
subject).
10. Pregnancy tests for women of childbearing age shall be negative;Both men and women
agreed to use effective contraception during treatment and during the subsequent 1
year.
11. Ability to understand and sign a written informed consent documen.
Exclusion Criteria:
1. Subjects are being treated with either corticosteroids (>10 mg daily prednisone
equivalent) or other immunosuppressive medications within 14 days of enrollment.
2. Received cytotoxic chemicals, monoclonal antibodies, or immunotherapy within 4 weeks
or 5 half-lives before enrollment;
3. Pregnant, lactating, or breastfeeding females;
4. Evidence of active uncontrolled viral, bacterial, or systemic fungal infection.
5. Known positive test result for human immunodeficiency virus (HIV) oracquired immune
deficiency syndrome (AIDS);Active infection of hepatitis B virus (HBV), or hepatitis
C virus (HCV);
6. History of allergy or intolerance to study drug components;
7. Prior organ allograft transplantations or allogeneic hematopoietic stem cell
transplantation;
8. Major surgery or trauma occurred within 28 days prior to enrollment, or major side
effects have not been recovered.
9. Known brain metastases or active central nervous system(CNS) has been involved
10. Previous or concurrent cancer within 5 years prior to treatment start except for
curatively treated cervical cancer in situ, non-melanoma skin cancer, local prostate
cancer after radical surgery ;
11. Any serious underlying medical (eg, pulmonary, renal,hepatic,gastrointestinal, or
neurological) or psychiatric condition or any issue that would limit compliance with
study requirements;
12. Vaccination within 30 days of study enrollment;
13. Previously received targeting CD70 therapy;
14. Being participating any other trials or withdraw within 4 weeks;
15. Researchers believe that other reasons are not suitable for clinicaltrials.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
China
Address:
City:
Beijing
Country:
China
Status:
Recruiting
Contact:
Last name:
Weidong Han, Ph.D
Phone:
010-66937231
Email:
hanwdrsw@sina.com
Contact backup:
Last name:
Yang Liu, M.D
Phone:
010-66939460
Email:
liuyang301blood@163.com
Start date:
July 15, 2023
Completion date:
December 31, 2026
Lead sponsor:
Agency:
Chinese PLA General Hospital
Agency class:
Other
Collaborator:
Agency:
UTC Therapeutics Inc.
Agency class:
Industry
Source:
Chinese PLA General Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05948033
