Status:
TERMINATED
RPM CD19-mbIL15-CAR-T Cells in Patient With Advanced Lymphoid Malignancies
Lead Sponsor:
Eden BioCell Ltd.
Collaborating Sponsors:
National Taiwan University Hospital
Conditions:
B-cell Acute Lymphoblastic Leukemia
Non-Hodgkin's Lymphoma, Relapsed
Eligibility:
All Genders
20-75 years
Phase:
PHASE1
Brief Summary
This is an open-label Phase 1 study to determine the feasibility, safety, and the recommended maximum tolerated Dose (MTD) of a single infusion of RPM CD19 mbIL15 CAR-T cells for adult patients. Appro...
Detailed Description
This is an open-label Phase 1 study to determine the feasibility, safety, and the recommended maximum tolerated Dose (MTD) of a single infusion of RPM CD19 mbIL15 CAR-T cells for adult patients. Appro...
Eligibility Criteria
Inclusion
- Inclusion Criteria for Enrollment:
- A subject may participate in the study if all the following criteria is met:
- Patients with CD19+ malignancies that are refractory to or relapsed after current standard treatment (including allogeneic or autologous HSCT) and not suitable for other treatment options, such as second-time HSCT. CD19+ malignancies include:
- Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia (ALL):
- Refractory ALL is defined as failure to achieve CR at the end of induction.
- Relapsed ALL is defined as reappearance of blasts in the blood or bone marrow (≥ 5%) or in any extramedullary site after a CR.
- Relapsed/Refractory B-cell originated Non-Hodgkin Lymphoma (NHL) including 1) de-novo diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma, 2) large-B cell lymphoma transformed from indolent lymphomas, 3) follicular lymphoma of all grades, 4) mantle cell lymphoma, and 5) CD20(+) high-grade B-cell lymphomas. Refractory disease for lymphoma is defined as:
- Progressive disease or stable disease lasting \< 6 months, as best response to most recent chemotherapy regimen; or disease progression or recurrence \< 12 months after prior autologous HSCT.
- Prior therapy must have included an anti-CD20 monoclonal antibody-containing regimen and an anthracycline-containing chemotherapy regimen
- For patients with transformed follicular lymphoma (TFL), prior chemotherapy for follicular lymphoma and subsequent refractory disease after transformation to DLBCL.
- At least one measurable lesion, demonstrating that the nodal lesion is ≥ 1.5 cm in the longest diameter or the extranodal lesion is ≥ 1.0 cm in the longest diameter, according to the Lugano Classification (2014).
- Patients must have received at least 2 prior lines of therapy. HSCT (allogeneic or autologous) can be accounted as one of the prior line therapy, and the subjects must have been at least 3 months from prior HSCT.
- Karnofsky Performance Scale ≥ 60
- Patient able to provide written informed consent for participating in the study
- Age ≥ 20 years and ≤ 75 years old at the time of providing informed consent
- Patients shall be at least 3 weeks from the last cytotoxic chemotherapy before apheresis. Short-acting targeted therapies (e.g., tyrosine kinase inhibitors) must be stopped \> 72 hours before apheresis.
- Monoclonal antibody use including Anti-CD20 therapy has been discontinued at least 4 weeks before leukapheresis and CAR-T cells infusion except for systemic inhibitory/stimulatory immune checkpoint therapy. Immune checkpoint therapy has been discontinued at least 3 half-lives before leukapheresis (e.g. ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists, etc.).
- Absolute lymphocyte count (ALC) ≥ 1.0x109/L and absolute number of CD3+ T cells (ATC) ≥ 0.3x109/L, absolute neutrophil count (ANC) ≥ 1.0 x109/L for lymphoma and ANC ≥ 0.5 x109/L for ALL, platelets ≥ 50.0 x109/L, hemoglobin ≥ 80.0 g/L within 7 days before apheresis.
- Adequate organ function demonstrated by the following:
- Renal: serum creatinine \<2 x upper limit of normal (ULN)
- Hepatic: ALT/AST ≤ 2.5 x ULN or ≤ 5 x ULN if documented liver metastases, total bilirubin ≤ 1.5 mg/dL, except in subjects with Gilbert's Syndrome in whom total bilirubin must be ≤ 3.0 mg/dL.
- Cardiac: no clinically significant ECG findings, hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram
- Pulmonary: baseline oxygen saturation \> 90% on room air
- 10\. Not receiving anti-thymocyte globulin (ATG), alemtuzumab, or other T-cell immunosuppressive antibodies, donor-lymphocyte infusion or T-cell infusion for the past 3 weeks before apheresis;
- Negative serology for Anti-HTLV-I / HTLV-II (DHTLV I/II)
- Exclusion Criteria for Enrollment
- A subject who met any of the following criteria is not eligible to enter the study:
- Received previous treatment with anti-CD19 therapy;
- Is with a history of CNS malignancy and/or active CNS diseases;
- Has previous or concurrent malignancies other than CD19+ malignancies;
- Has active neurological, autoimmune, or inflammatory disorders;
- Has clinically significant cardiac diseases, or cardiac arrhythmia not controlled with medical treatment;
- Has cardiac involvement with lymphoma;
- Has any active infections, conditions, and diseases that may interfere with the assessment of safety and efficacy of the study deemed by the investigator or designee;
- Received live vaccine within 6 weeks of the screening
- Received radiation therapy within 2 weeks of the planned CAR-T cells infusion;
- Is with positive serology for HIV;
- Is with positive hepatitis B or hepatitis C infection, defined as positive HBs Ag or positive Anti-HCV Ab;
- Active graft versus host disease (GVHD) ≥ grade 2 using the CIBMTR Acute GVHD Grading System or requiring systemic steroid therapy greater than physiologic dosing; Note: Overall grading of GVHD is based on the criteria published by Przepiorka et al., Bone Marrow Transplant 1995; 15(6):825-8, see the GVHD Grading and Staging table at CIBMTR Forms Instruction Manual (Last updated: 2020/03/10), page 301-303 (Available at https://www.cibmtr.org/manuals/fim, accessed on 08 Apr 2020).
- Use of investigational medicinal product within 30 days before the screening;
- Positive beta HCG in female of child-bearing potential (defined as not post-menopausal for 12 months) or history of previous surgical sterilization or lactating females.
- Patients with known allergy to mouse products or cetuximab.
- Inclusion Criteria for Lymphodepletion and T-Cell Infusion:
- Prior to Lymphodepletion (LD):
- Patients must have no evidence of clinically significant infection;
- No acute neurological toxicity \>grade 1 (with the exception of peripheral sensory neuropathy) prior to conditioning chemotherapy;
- No clinically significant cardiac dysfunction;
- Serum creatinine \< 2x ULN;
- No evidence of grade ≥2 acute GVHD;
- Pulmonary: oxygen saturation \> 90% on room air;
- Adequacy of T cells apheresis products to manufacture CAR-T product.
- Prior to CAR-T cells infusion:
- Patients shall be at least 4 weeks from the last cytotoxic chemotherapy (excluding the study mandated lymphodepleting chemotherapy) before infusion. Short-acting targeted therapies (e.g., tyrosine kinase inhibitors) must be stopped \> 72 hours before infusion.
- At least 4 weeks from anti-thymocyte globulin (ATG), alemtuzumab, or other T-cell immunosuppressive antibodies, donor-lymphocyte infusion or T-cell infusion;
- Steroids, if given as GVHD therapy, must be stopped \>72 hours prior to infusion. However, the following physiological replacement doses of steroids are allowed: \< 6-12 mg/m2/day hydrocortisone or equivalent.
- Non-hematologic toxicity grade ≥2 (CTCAE version 5) related to the lymphodepleting chemotherapy until the toxicity has resolved to grade ≤1 and the subject is afebrile;
- No grade \>2 neurologic, pulmonary, cardiac, gastrointestinal, renal, or hepatic (excluding albumin) toxicity;
- Adequacy of the CAR-T cells for infusion.
- Exclusion Criteria For Lymphodepletion and T-Cell Infusion:
- A subject who meets any of the following criteria should not undergo LD or infusion of CAR-T cells.
- New onset of cardiac arrhythmia not uncontrolled with medications;
- Hypotension warrants the use of vasopressor;
- Active infections within 1 week prior to CAR-T infusion that necessitate the use of oral or intravenous anti-infective treatments; subjects with ongoing use of prophylactic antibiotics, antifungals, or antivirals are eligible as long as there is no evidence of active infection.
- Presence of CNS or neurological abnormalities;
- Received HSCT after screening or planned to receive HSCT during the study period;
- Any conditions not suitable for the CAR-T cells infusion in the PI or designee's judgement.
Exclusion
Key Trial Info
Start Date :
March 2 2021
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
May 12 2022
Estimated Enrollment :
2 Patients enrolled
Trial Details
Trial ID
NCT04844086
Start Date
March 2 2021
End Date
May 12 2022
Last Update
May 18 2022
Active Locations (1)
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1
National Taiwan University Hospital
Taipei, Taiwan