Study of CART Cell (MB-CART19.1) in Patients With Relapsed or Refractory CD19 Positive NHL

Official title

A Phase II Study of CART Cell (MB-CART19.1) in Patients With Relapsed or Refractory CD19 Positive NHL

Overview

This is a Prospective Single Center, open label, Non-randomized, Single Arm, Single Dose, Phase II Clinical Trial. Adult patients \>18-year-old with CD19+ Non-Hodgkin lymphoma are eligible for the study if they meet eligibility criteria. Patients will receive a fresh single dose of MB-CART-19.1 and will be followed for 12 months and evaluated for efficacy and safety.

Detailed description

This is a prospective single center, open label, non-randomized, single arm, single dose, optimal 2-stage Simon design, and Phase II clinical trial. The trial includes Adult patients \> 18-year-old and up to 75 years old, with CD19+ non-Hodgkin lymphoma including diffuse Large B-cell Lymphoma, primary mediastinal B-cell lymphoma and relapsed refractory follicular lymphoma.

Single infusion of freshly prepared MB-CART19.1 cells manufactured according to Miltinyi Biotec product manufacturing guidelines and good manufacturing product (GMP) of KHCC manufacturing standard operating procedures (SOPs).

The patients will receive one infusion of the MB-CART19.1 product in infusion solution at a final volume adapted to the patients' weight, over a time of approx. 5-20 minutes (intravenous infusion via a large peripheral vein or central line).

The objective of this trial is to assess the efficacy and safety of ex vivo generated MB-CART19.1 in adult patients with relapsed or refractory CD19 positive Non-Hodgkin lymphoma including diffuse Large B-cell Lymphoma, primary mediastinal B-cell lymphoma and relapsed refractory follicular lymphoma

Interventions

• Other MB-CART-19.1
  The leukapheresed product will be used for the individual manufacturing of MB-CART19.1 by using the automated closed CliniMACS Prodigy System. CD4+ and CD8+ T-cells will be selected, enriched and activated, followed by lentivirus-based transduction with the CD19 CAR construct. Then the MB-CART19.1 transduced T cells will be expanded and finally formulated.

Primary outcome measures

• overall response rate [Time frame: on week 4 and at month 3 in patients not achieving CR on week 4]

Secondary outcome measures (8)

• Safety and toxicity [Time frame: From enrolment to the end of follow up at one year]
• CRS [Time frame: From enrolment to the end of follow up at one year]
• Disease-free survival [Time frame: at 1 year after receiving study treatment]
• Duration of response [Time frame: From enrolment to end of follow up at one year]
• ICANS [Time frame: From enrolment to the end of follow up at one year]
• relapse rate [Time frame: From enrolment to the end of follow up at one year]
• time to relapse [Time frame: From enrolment to the end of follow up at one year]
• overall survival [Time frame: at 1 year after receiving study treatment]

Eligibility criteria

Inclusion criteria

• Eligible patients with a diagnosis of aggressive NHL:

• Patients after progression on at least one standard chemotherapy and one salvage regimen or
• Patients considered for alloSCT but are found ineligible or
• Patients who have relapsed post alloSCT at least 100 days post-transplant, with no evidence of active GVHD, and no longer taking immunosuppressive agents for at least 30 days prior to enrollment.
• Patients with CNS disease (excluding isolated CNS lymphoma) are eligible only if disease has been successfully cleared at the time of inclusion.
• CD19 expression must be detected on the malignant cells by flow cytometry or immunohistochemistry
• Age > 18 year up to 75 years old (if deemed fit by treating investigator);
• Baseline absolute CD3+ T cell count by FACS ≥100/µl;
• ECOG performance score of 0-2 at screening;
• No active Hepatitis B, Hepatitis C, HIV I/II
• No childbearing potential or negative pregnancy test at screening within 7 days from starting lymphodepletion chemotherapy and before bridging chemotherapy in women with childbearing potential;
• Signed and dated informed consent, before conduct of any trial-specific procedure.

Exclusion criteria

• Residual CNS disease
• Current autoimmune disease, or history of autoimmune disease with potential CNS involvement;
• Active clinically significant CNS dysfunction (including but not limited to uncontrolled seizure disorders, cerebrovascular ischemia or hemorrhage, dementia, paralysis)
• History of an additional malignancy other than non-melanoma skin cancer or carcinoma in situ unless disease free for ≥3 years;
• Pulmonary function: Patients with pre-existing severe lung disease or DLCO of less than 50% or active pulmonary infiltrates on imaging studies.
• Cardiac function: left ventricular ejection faction <50% by echocardiogram,
• Renal function: Creatinine clearance <50 mL/min/1.73 m2, by Cockcroft-Gault formula (Cockcroft and Gault 1976) for patients ≥18 years.
• Liver function: patients with serum bilirubin ≥3 times upper limit of or AST or ALT > 5 times upper limit of normal, unless due to lymphoma liver infiltration in the estimation of the investigator.
• Rapidly progressive disease that in the estimation of the investigator would compromise ability to complete study therapy;
• Pregnant or breast-feeding females
• Medications: systemic chemotherapies, corticosteroids with the exception of physiologic replacement dosing, Fludarabine/clofarabine or immunosuppressive (Calcineurin inhibitors) drugs and antibodies or investigational drugs or donor lymphocyte transfusions or radiation therapy within 30 days prior to apheresis, and rituximab within 2 weeks with the exception of Intrathecal chemotherapy is allowed prior to treatment, but should be discontinued 10 days prior to-CART19 infusion to limit the risk of neurotoxicities;
• Patients of child-bearing or fathering potential not willing to practice an effective form of birth control from the time of enrollment and for three months after dosing of the CARTs;
• Concurrent participation in another interventional trial that could interact with this trial, e.g. CAR T trials.
• Other investigational treatment within 4 weeks before CARTs infusion;
• Cerebral dysfunction, legal incapacity of adult patients;
• Committal to an institution on judicial or official order.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Jordan · 1 center

• King Hussein Cancer Center — Amman

Identifiers

NCT: NCT07271121 · 24 KHCC 192

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗