This study has 2 parts. The main aim of Part 1 is to check for side effects from TAK-007 in adults with relapsed or refractory (r/r) B-cell Non-Hodgkin Lymphoma (NHL), The main aim of Part 2 is to learn whether lymphoma disease responds to treatment with TAK-007 in adults with r/r B-cell NHL or iNHL. Participants will receive 3 days of chemotherapy to reduce a type of white blood cells called lymphocytes, in the blood. This is called lymphodepleting chemotherapy (LDC) or lymphodepletion. After LDC, patients will receive a single injection of TAK-007 or three weekly injections of TAK-007 (multi-dose injection). After this, participants will regularly visit the clinic for check-ups.
The product being tested in this study is called TAK-007. TAK-007 is being tested to evaluate the safety and tolerability in adult participants with r/r B-cell NHL. The study will include 2 parts: Part 1 (Dose escalation and dose expansion) and Part 2. In Part 1, dose escalation cohorts' participants will receive TAK-007 as follows: Part 1 dose escalation: * Part 1: Dose escalation: TAK-007 - 200×10\^6 CD19-CAR+ Viable NK (Natural Killer) Cells (±30%) * Part 1: Dose escalation: TAK-007 - 800×10\^6 CD19-CAR+ Viable NK Cells (±25%) In Part 1 dose expansion phase, separate expansion cohorts for LBCL and iNHL (Cohorts 1A \[LBCL 3L+\] and 2A \[iNHL 3L+\]) and two additional dose expansion cohorts with a multi-dose regimen will be added (i.e., Cohort 1B and 1C) to evaluate more than 1 doses of TAK-007 after a 3-day regimen of lymphodepleting chemotherapy. Part 1 dose expansion cohorts' participants will receive TAK-007 as follows: * Part 1: Dose expansion: Cohort 1 (LBCL 3L+): TAK-007 - 800×10\^6 CD19-CAR+ Viable NK Cells on Day 0 of the study. * Part 1: Dose expansion: Cohort 2 (iNHL 3L+): TAK-007 - 800×10\^6 CD19-CAR+ Viable NK Cells on Day 0 of the study. Based on the data in Part 1, a single TAK-007 dose level will be selected by the sponsor and investigators as the recommended phase 2 dose (RP2D). Once RP2D is determined, participants will be enrolled in Part 2 of the study in the following cohorts: * Cohort 1: TAK-007 (LBCL) * Cohort 2: TAK-007 (iNHL) This multi-center trial will be conducted worldwide. Part 1 of the study will be conducted in the US, and Part 2 will be conducted worldwide. The overall time to participate in this study is 5 years. Participants will make multiple visits to the clinic and will enroll in a separate, long-term, follow-up study for continued safety assessments for up to 15 years after TAK-007 administration.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
27
TAK-007 intravenous injection.
Fludarabine and cyclophosphamide as per standard of care.
University of Alabama at Birmingham
Birmingham, Alabama, United States
Cedars Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
Los Angeles, California, United States
MedStar Georgetown University Medical Center
Washington D.C., District of Columbia, United States
Sylvester Comprehensive Cancer Center University of Miami Hospitals and Clinics
Miami, Florida, United States
Northside Hospital
Atlanta, Georgia, United States
Northwestern Memorial Hospital
Chicago, Illinois, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States
Columbia University Medical Center
New York, New York, United States
Montefiore Medical Center
The Bronx, New York, United States
DUHS Duke Blood Cancer Center
Durham, North Carolina, United States
...and 5 more locations
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. TEAE is defined as any event emerging or manifesting at or after the initiation of treatment with a study intervention or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the study intervention or medicinal product.
Time frame: Up to 24 months
Number of Participants With Clinically Significant Changes in Laboratory Parameters
Laboratory parameters included hematology, clinical chemistry, serum immunoglobulin and urinalysis tests.
Time frame: Up to 24 months
Number of Participants With Notable Changes in Vital Signs
Vital signs included body temperature (oral or tympanic measurement), sitting blood pressure (after the participant had rested for at least 5 minutes), and pulse rate (beats per minute \[bpm\]).
Time frame: Up to 24 months
ORR Per Investigator
ORR is defined as the percentage of participants with CR or PR as best response to treatment, determined by the investigator per the Lugano 2014 criteria after TAK-007 administration. CR is defined as percentage of participants with target nodes/nodal masses must regress to ≤1.5 cm in the longest transverse diameter of all lesions and no extralymphatic sites of disease. PR is defined as ≥50% decrease in sum of the product of the perpendicular diameters of up to 6 target measurable nodes and extranodal sites; absent/normal, regressed, but no increase in nonmeasured lesion; Spleen must have regressed by \>50% in length beyond normal.
Time frame: Up to 24 months
Complete Response (CR) Per Investigator
CR is defined per Lugano 2014 criteria as percentage of participants with target nodes/nodal masses must regress to ≤1.5 cm in the longest transverse diameter of all lesions and no extralymphatic sites of disease.
Time frame: Up to 24 months
Duration of Response (DOR) Per Investigator
DOR is defined only for participants who experienced objective response (complete response or partial response) and is the time from the date of first documented objective response to the date of first documented disease progression or death, whichever comes first. Participants not meeting the criteria for progression or death will be censored at the last disease assessment.
Time frame: Up to 24 months
Progression-free Survival (PFS) Per Investigator
Progression-free survival is defined as the time from TAK-007 administration to the date of disease progression or death from any cause, whichever comes first. Participants who do not have disease progression or die were censored at the last disease assessment. Participants who do not have postbaseline disease assessment prior to new anticancer therapy (excluding SCT) in the absence of death were censored at the dosing date of TAK-007.
Time frame: Up to 24 months
Overall Survival (OS)
OS is defined as the time from TAK-007 administration to the date of death. Participants who did not die were censored at the last contact date.
Time frame: Up to 24 months
Cmax - Maximum Observed Blood Concentration of TAK-007
The unit of measure 'copies per microgram' indicates copies of TAK-007 transgene per micrograms of genomic deoxyribonucleic acid (DNA).
Time frame: At 1 hour (±15 minutes) predose and postdose (Day 0) and once on Days 1, 3, 7, 10, 14, 21, 28/Month 1, Months 2, 3, 4, 6, 9, 12, 18, 24
Tmax - Time of First Occurrence of Cmax of TAK-007
Time frame: At 1 hour (±15 minutes) predose and postdose (Day 0) and once on Days 1, 3, 7, 10, 14, 21, 28/Month 1, Months 2, 3, 4, 6, 9, 12, 18, 24
Tlast - Time of Last Measurable Concentration Above the Lower Limit of Quantitation of TAK-007
Time frame: At 1 hour (±15 minutes) predose and postdose (Day 0) and once on Days 1, 3, 7, 10, 14, 21, 28/Month 1, Months 2, 3, 4, 6, 9, 12, 18, 24
AUClast - Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration of TAK-007
The unit of measure 'day\*copies/µg' indicates day\*copies of TAK-007 transgene per µg of genomic DNA.
Time frame: At 1 hour (±15 minutes) predose and postdose (Day 0) and once on Days 1, 3, 7, 10, 14, 21, 28/Month 1, Months 2, 3, 4, 6, 9, 12, 18, 24
Concentration of Interleukin (IL)-15 and Other Soluble Immune Factors in Plasma Over Time
Concentration of IL-15 and soluble immune factors (eg, Interferon (IFN)-gamma (γ) and IL-6) in plasma over time were reported.
Time frame: Baseline, pre-dose (Day 0) and post-dose at Days 1, 7, 14, 21, 28 and Months 2,3,4,6,9,12
Percentage of Participants With B-cell Aplasia Before and After TAK-007 Administration
B-cell aplasia is defined as \<50 B-cells per microliters (µl) of blood.
Time frame: Pre-dose at Days -5, -4, 0 and post-dose at Days 0, 7, 28 and Months 2, 3, 4, 6, 9, 12
Percentage of Participants With Detectable Anti-human Leukocyte Antigen (HLA) and Anti-chimeric Antigen Receptor (CAR) Antibodies Before (Prevalence) and After (Incidence) TAK-007 Administration Over Time
Time frame: Up to 12 months
Percentage of Participants With Positive Replication Competent Retrovirus (RCR) Test Results Before (Prevalence) and After (Incidence) TAK-007 Administration Over Time
Time frame: Up to 60 months
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