Trial Title:
Study for Subjects With Relapsed/Refractory Non- Hodgkin Lymphoma
NCT ID:
NCT05618925
Condition:
Non Hodgkin's Lymphoma Refractory/Relapsed
Conditions: Official terms:
Lymphoma
Lymphoma, Non-Hodgkin
Cyclophosphamide
Rituximab
Fludarabine
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Single Group Assignment
Intervention model description:
Subjects in both cohorts will initially receive lymphodepleting chemotherapy followed by
a single 4 week cycle of the CD19 t haNK single-agent regimen. Following a 1-week rest
period, subjects will then receive lymphodepleting chemotherapy followed by a single
4-week cycle of CD19 t-haNK in combination with rituximab (cohort A) or in combination
with rituximab and N-803 (cohort B). Following a second 1-week rest period, subjects will
receive up to 4 repeated 4 week cycles of CD19 t haNK in combination with rituximab
(cohort A) or in combination with rituximab and N 803 (cohort B) without lymphodepleting
chemotherapy.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
N803
Description:
nogapendekin alfa inbakicept (also known as ALT-803; recombinant human superagonist
interleukin-15 (IL-15) complex [also known as IL 15N72D:IL-15RαSu/IgG1 Fc complex])
Arm group label:
Arm B
Other name:
Anktiva
Intervention type:
Biological
Intervention name:
CD19t-haNK suspension
Description:
Derived from the parental NK-92 (aNK) cell line, CD19 t-haNK is a human, allogeneic, NK
cell line that has been engineered to express a CAR targeting CD19. Similar to the haNK
cell line, CD19 t haNK has also been engineered to produce endoplasmic reticulum-retained
IL 2 and the high-affinity (158V) variant of the Fcγ receptor (FcγRIIIa/CD16a), and
thereby has enhanced CD16-targeted ADCC capabilities. CD19 t-haNK is similar to PD L1
t-haNK, differing only in the CAR that is expressed (CD19 vs PD-L1).
Arm group label:
Arm A
Arm group label:
Arm B
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Cyclophosphamide is a synthetic antineoplastic drug chemically related to the nitrogen
mustards. The chemical name for cyclophosphamide is
2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate and
has the molecular formula C7H15Cl2N2O2P•H2O and a molecular weight of 279.1.
Arm group label:
Arm A
Arm group label:
Arm B
Other name:
Cytoxan
Intervention type:
Drug
Intervention name:
Fludarabine
Description:
Fludarabine phosphate is a fluorinated nucleotide analog of the antiviral agent
vidarabine, 9-β-D-arabinofuranosyladenine (ara-A) that is relatively resistant to
deamination by adenosine deaminase. The chemical name for fludarabine phosphate is
9H-Purin-6-amine, 2-fluoro-9-(5-0-phosphono β-D-arabino-furanosyl) (2-fluoro-ara-AMP).
The molecular formula of fludarabine phosphate is C10H13FN5O7P and it has a molecular
weight of 365.2.
Arm group label:
Arm A
Arm group label:
Arm B
Other name:
Fludara
Intervention type:
Drug
Intervention name:
Rituximab
Description:
Rituximab is a genetically engineered chimeric murine/human monoclonal IgG1 kappa
antibody directed against the CD20 antigen. Rituximab has an approximate molecular weight
of 145 kD and has a binding affinity for the CD20 antigen of approximately 8.0 nM.
Arm group label:
Arm A
Arm group label:
Arm B
Other name:
Rituxan
Summary:
Open-label, Phase 1 Study of CD19 t-haNK as a Single Agent and in Combination With an
IL-15 Superagonist (N-803) and Rituximab in Subjects With Relapsed/Refractory Non-Hodgkin
Lymphoma. Up to 20 subjects will be enrolled and randomized 1:1 to 1 of 2 cohorts, as
outlined below. The initial 3 subjects will be sequentially enrolled in a staggered
fashion, with a 7 day interval between each subject to enable the capture and monitoring
of any acute and subacute toxicities.
Detailed description:
This is a phase 1, first-in-human (FIH), open-label study to evaluate the safety of CD19
t-haNK as a single agent and the safety and preliminary efficacy of CD19 t haNK in
combination with rituximab only and in combination with rituximab and N 803 in subjects
with R/R NHL.
Up to 20 subjects will be enrolled and randomized 1:1 to 1 of 2 cohorts, as outlined
below. The initial 3 subjects will be sequentially enrolled in a staggered fashion, with
a 7 day interval between each subject to enable the capture and monitoring of any acute
and subacute toxicities.
Subjects in both cohorts will initially receive lymphodepleting chemotherapy followed by
a single 4 week cycle of the CD19 t haNK single-agent regimen. Following a 1-week rest
period, subjects will then receive lymphodepleting chemotherapy followed by a single
4-week cycle of CD19 t-haNK in combination with rituximab (cohort A) or in combination
with rituximab and N-803 (cohort B). Following a second 1-week rest period, subjects will
receive up to 4 repeated 4 week cycles of CD19 t haNK in combination with rituximab
(cohort A) or in combination with rituximab and N 803 (cohort B) without lymphodepleting
chemotherapy.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥ 18 years old.
2. Able to understand and provide a signed informed consent that fulfills the relevant
Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
3. Histologically documented CD19- and CD20-positive B-cell NHL with the following
specific criteria:
1. Have active disease after ≥ 2 lines of cytotoxic chemotherapy.
2. Have received rituximab or another anti-CD20 antibody.
3. Have either failed autologous transplant or are ineligible to receive
autologous transplant.
4. Have measurable disease by Lugano classification documented within 8 weeks of
the time of consent, defined as nodal lesions > 15 mm in the long axis or
extranodal lesions > 10 mm in long and short axis, or bone marrow involvement
that is biopsy proven.
5. Have CD19- and CD20-positive disease on most recent biopsy performed (a repeat
biopsy is not mandatory for this study except as noted below). A minimum of 5%
CD19 and CD20 positivity by immunohistochemistry or flow cytometry on prior or
repeat biopsy is required.
4. History of central nervous system (CNS) involvement with cerebral spinal fluid (CSF)
analysis following magnetic resonance imaging (MRI) brain and lumbar puncture
showing no evidence of CNS involvement by cytology and flow cytometry.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
6. Expected survival > 12 weeks.
7. Willing and able to have central line placed for study drug infusions.
8. Stated willingness to comply with study procedures.
9. Able to attend required study visits and return for adequate follow-up, as required
by this protocol.
10. Agreement to practice effective contraception for female subjects of child-bearing
potential and nonsterile males. Female subjects of child-bearing potential must
agree to use effective contraception while on study and for at least 5 months after
the last dose of study drug. Nonsterile male subjects must agree to use a condom
while on study and for up to 5 months after the last dose of study drug. Effective
contraception includes surgical sterilization (eg, vasectomy, tubal ligation), two
forms of barrier methods (eg, condom, diaphragm) used with spermicide, intrauterine
devices (IUDs), and abstinence.
Exclusion Criteria:
1. Known hypersensitivity to any component of the study medication(s), including
anaphylactic reaction to sulfur-containing medications.
2. Known allergy to albumin (human) or dimethyl sulfoxide (DMSO).
3. Serious uncontrolled concomitant disease that would contraindicate the use of the
investigational drug used in this study or that would put the subject at high risk
for treatment-related complications.
4. History of significant autoimmune disease OR active, uncontrolled autoimmune
phenomenon: such as systemic lupus erythematous, Wegner's glomerulonephritis,
autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura requiring steroid
therapy defined as > 20 mg of prednisone or equivalent daily.
5. History of allogeneic hematopoietic stem-cell transplantation (HSCT) or allogeneic
chimeric antigen receptor (CAR) T therapy within 6 months of day 1 or require
ongoing systemic graft versus host disease (GvHD) therapy.
6. Anti-CD19 or anti-CD20 antibody treatment within 4 weeks of cell infusion.
7. Live vaccine < 6 weeks prior to starting lymphodepleting chemotherapy.
8. History of receiving allograft organ transplant requiring immunosuppression.
9. Subjects post solid organ transplant who develop high grade lymphomas or leukemias.
10. Known lymphomatous involvement of the CNS, including the parenchyma or
leptomeninges.
11. Nonmalignant CNS disease (eg, stroke, epilepsy, vasculitis, or neurodegenerative
disease).
12. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative
colitis).
13. Inadequate organ function, evidenced by the following laboratory results:
1. ANC < 1000 cells/mm3.
2. Platelet count < 100,000 cells/mm3.
3. Total bilirubin ≥ 1.5 × the upper limit of normal (ULN; unless the subject has
documented Gilbert's syndrome or indirect hyperbilirubinemia).
4. Aspartate aminotransferase (AST [SGOT])/ALT (SGPT) ≥ 2.5 × ULN.
5. Alkaline phosphatase (ALP) levels ≥ 2.5 × ULN (or ≥ 5 × ULN in subjects with
bone metastases).
6. Serum creatinine > 1.6 mg/dL. Each study site should use its institutional ULN
to determine eligibility.
14. Uncontrolled hypertension (systolic > 160 mm Hg and/or diastolic > 110 mm Hg) or
clinically significant (ie, active) cardiovascular disease, cerebrovascular
accident/stroke, or myocardial infarction within 6 months prior to first study
medication; unstable angina; congestive heart failure of New York Heart Association
grade 2 or higher; or serious cardiac arrhythmia requiring medication.
15. Current chronic daily treatment (continuous for > 3 months) with systemic
corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone),
excluding inhaled steroids. Short-term steroid use to prevent IV contrast allergic
reaction or anaphylaxis in subjects who have known contrast allergies is allowed.
16. Currently taking any medication(s) (herbal or prescribed) known to have an adverse
drug reaction with any of the study medications.
17. History of human immunodeficiency virus (HIV) with current CD4+ T-cell count < 500
cells/μL..
18. Chronic carriers of hepatitis B virus (HBV) infection that is currently hepatitis B
surface antigen (HBsAg) positive. NOTE: Subjects who have a history of HIV/HBV or
who are seropositive will require testing for Infectious Disease Markers (IDM).
19. Concurrent active malignancy other than basal or squamous cell carcinomas of the
skin.
20. Assessed by the Investigator to be unable or unwilling to comply with the
requirements of the protocol.
21. Women who are pregnant or breastfeeding. A negative urine or serum pregnancy test in
women of child bearing potential is required at screening and again within 48 hours
prior to lymphodepleting chemotherapy
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Hoag Memorial Hospital
Address:
City:
Newport Beach
Zip:
92663
Country:
United States
Status:
Recruiting
Contact:
Last name:
Patrice Jones
Phone:
949-764-5501
Email:
Patrice.Jones@hoag.org
Investigator:
Last name:
Pooja Motwani, MD
Email:
Principal Investigator
Start date:
November 1, 2024
Completion date:
March 15, 2027
Lead sponsor:
Agency:
ImmunityBio, Inc.
Agency class:
Industry
Source:
ImmunityBio, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05618925
