Cell Therapy with Anti-CD19 CAR-NK Cells in Patients with Relapsed or Resistant B-ALL
Cell Therapy with Anti-CD19 CAR-NK Cells in Patients with Relapsed or Resistant B-Acute Lymphocytic Leukemia
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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-
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Tabriz, Iran, Islamic Republic of
- Shahid Ghazi Hospital, Tabriz university of medical sciences
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Contact:
- Masoud Soleimani
- Phone Number: 09122875993
- Email: soleimani.masoud@gmail.com
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Eligible diseases: Acute lymphocytic leukemia (ALL CD19+). Patients 3 years of age or older, and must have a life expectancy > 12 weeks. Eastern cooperative oncology group (ECOG) performance status of 0-2 or karnofsky performance status (KPS) score is higher than 60.
Females of child-bearing potential must have a negative pregnancy test and all subjects must agree to use an effective method of contraception for up to two weeks after the last infusion of CAR NK cells.
Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: White blood cell count (WBC) ≥ 2500c/ml, Platelets ≥ 50×10^9/L, Hb ≥ 9.0g/dL, lymphocyte (LY) ≥ 0.7×10^9/L, LY% ≥ 15%, Alb ≥ 2.8g/dL, serum lipase and amylase < 1.5×upper limit of normal, serum creatinine ≤ 2.5mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5×upper limit of normal, serum total bilirubin ≤ 2.0mg/dL. These tests must be conducted within 7 days prior to registration.
Ability to give informed consent.
Exclusion Criteria:
Pregnant or nursing women may not participate. Active HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at the time of screening.
Serious illness or medical condition which would not permit the patient to be managed according to the protocol, including active uncontrolled infection, major cardiovascular, coagulation disorders, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive/restrictive pulmonary disease, or psychiatric or emotional disorders.
History of severe immediate hypersensitivity to any of the agents including cyclophosphamide, fludarabine, or aldesleukin.
Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
The existence of unstable or active ulcers or gastrointestinal bleeding. Patients need anticoagulant therapy (such as warfarin or heparin). Patients need long-term antiplatelet therapy (aspirin at a dose > 300mg/d; clopidogrel at a dose > 75mg/d).
Patients using fludarabine or cladribine chemotherapy within 3 months prior to leukapheresis.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Experimental: Acute lymphocytic leukemia, in relapse
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Ten eligible patients with relapsed Acute Lymphoblastic Leukemia will be enrolled based on inclusion criteria and informed consent.
After conditioning with Fludarabine and Cyclophosphamide, patients will receive a single infusion of anti-CD19 CAR NK cells with close monitoring using one of the following dose levels: • Dose Level 1: 1×10^7/Kg • Dose Level 2: 5×10^7/Kg • Dose Level 3: 1×10^8/Kg Safety Assessment: Adverse events will be recorded and graded.
Laboratory parameters and cytokine release syndrome (CRS) markers will be closely monitored.
Efficacy Evaluation: Response assessments will follow International Lymphoma Party (LWP) Group guidelines, including complete response (CR), partial response (PR), stable disease (SD), and progressive disease.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Incidence of dose-limiting toxicity (DLTs)
Time Frame: 4 weeks
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Incidence of dose-limiting toxicity (DLTs) within 4 weeks after infusion, characterized by >= Grade 3 signs/symptoms according to CTCAE v4.03, to assess safety and tolerability.
|
4 weeks
|
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Assessment of Maximum Tolerated Dose (MTD)
Time Frame: 4 weeks
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4 weeks
|
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Overall Remission Rate (ORR)
Time Frame: 8 weeks
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Overall Remission Rate (ORR) two months after infusion, assessed using International lymphoma party (LWP) Group
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8 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Progression-free survival (PFS)
Time Frame: 48 weeks
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Assessed using International Lymphoma Working Party (LWP) criteria
|
48 weeks
|
|
Duration of Response (DOR)
Time Frame: 48 weeks
|
Duration of Response (DOR) for up to 12 months, Assessed using International Lymphoma Working Party (LWP) criteria
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48 weeks
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 75358
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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