SENTI-202 for Blood Cancers
Recruiting in Palo Alto (17 mi)
+7 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Senti Biosciences
Disqualifiers: Leukemia, MDS-f, CNS disease, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This is an open-label study of the safety, biodynamics, and anti-cancer activity of SENTI-202 (an off-the-shelf logic gated CAR NK cell therapy) in patients with CD33 and/or FLT3 expressing blood cancers, including AML and MDS.
Do I need to stop my current medications for the SENTI-202 trial?
The trial protocol does not specify if you need to stop your current medications, but it mentions that certain anti-cancer therapies used within a specific time before the study are not allowed. It's best to discuss your current medications with the trial team to see if any adjustments are needed.
What safety data is available for SENTI-202 or similar treatments in humans?
Fedratinib, a treatment similar to SENTI-202, has been studied in patients with myelofibrosis and showed some common side effects like diarrhea, nausea, anemia (low red blood cell count), and vomiting. Serious side effects included one case of reversible liver failure and a rare brain condition called Wernicke's encephalopathy, but these were not common. Overall, fedratinib has shown an acceptable safety profile in clinical trials.
12345Eligibility Criteria
This trial is for adults with blood cancers like AML or MDS that have come back after treatment. They must have tried at least one, but no more than two or three treatments (depending on the condition), and their cancer cells need to show CD33 or FLT3 markers. Participants should be fairly active (ECOG score 0-1) and have decent organ function.Inclusion Criteria
I am fully active or can carry out light work.
My leukemia has specific mutations and I've had 1-3 standard treatments.
My MDS has returned or didn't respond to treatment, and I've had 1-2 prior treatments.
I have a blood cancer and have received at least one standard treatment.
Exclusion Criteria
I have leukemia in my brain or active brain disease.
My cancer involves organs outside the bone marrow without signs of returning in the blood.
I have MDS with fibrosis or a genetic condition that responds to chemo for AML.
I had a stem cell transplant less than 100 days ago.
My leukemia is specifically diagnosed with a genetic abnormality in the APML-RARA gene.
I have previously received NK or CAR T cell therapy.
Participant Groups
SENTRI-202, a new type of cell therapy using modified natural killer (NK) cells designed to target cancer cells in patients with specific proteins on their leukemia or tumor cells, is being tested for safety and effectiveness.
1Treatment groups
Experimental Treatment
Group I: SENTI-202 CAR NK cell therapyExperimental Treatment1 Intervention
Part 1 Dose Finding: Sequential cohorts will receive doses of SENTI-202 using a modified 3+3 study design to determine the recommended phase 2 dose (RP2D). The starting dose will be 1 billion cells. Other doses may be explored depending on study data.
Part 2 Cohort Expansion: After determination of the RP2D, additional subjects will be enrolled in disease-specific expansion cohorts at that dose to further explore safety, biodynamics, and anti-cancer activity of SENTI-202
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
MD Anderson Cancer CenterHouston, TX
UCLA Medical CenterLos Angeles, CA
Colorado Blood Cancer InstituteDenver, CO
TriStar Bone Marrow TransplantNashville, TN
More Trial Locations
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Who is running the clinical trial?
Senti BiosciencesLead Sponsor
References
A phase 2 randomized dose-ranging study of the JAK2-selective inhibitor fedratinib (SAR302503) in patients with myelofibrosis. [2022]In this phase 2 open-label randomized study, 31 patients with intermediate-2 or high-risk myelofibrosis received fedratinib 300, 400 or 500 mg once daily in consecutive 4-week cycles. Mean spleen volume reductions at 12 weeks (primary end point) were 30.3% (300 mg), 33.1% (400 mg) and 43.3% (500 mg). Spleen response rates (patients achieving ⩾35% spleen reduction) at 12/24 weeks were 30%/30% (300 mg), 50%/60% (400 mg) and 64%/55% (500 mg), respectively. By 4 weeks, improvements in myelofibrosis (MF)-associated symptoms were observed. At 48 weeks, 68% of patients remained on fedratinib and 16% had discontinued because of adverse events (AEs). Common grade 3/4 AEs were anemia (58%), fatigue (13%), diarrhea (13%), vomiting (10%) and nausea (6%). Serious AEs included one case of reversible hepatic failure and one case of Wernicke's encephalopathy (after analysis cutoff). Fedratinib treatment led to reduced STAT3 phosphorylation but no meaningful change in JAK2V617F allele burden. Significant modulation (P
Profile of pacritinib and its potential in the treatment of hematologic disorders. [2022]Pacritinib (previously known as SB-1518) is an innovative selective inhibitor of Janus kinase 2 and FMS-related tyrosine kinase 3 providing potential in the treatment of hematological malignancies such as myeloproliferative neoplasias, acute myeloid leukemia, and various lymphomas. Pacritinib has potent antiproliferative activity in Janus kinase 2 and/or FMS-related tyrosine kinase 3 activity-dependent cell lines and an ability to promote apoptosis and inhibit the signal transducers and activators of transcription (STAT) pathway. Pharmacokinetic studies have indicated a good per os bioavailability and favorable kinetic parameters. To date, promising results have been produced in five completed early-phase clinical trials in which pacritinib has been studied. Pacritinib displayed interesting activity and an acceptable safety profile, with mild to moderate gastrointestinal disorders being its most common adverse effects.
Association between acute myelogenous leukemia and thrombopoietin receptor agonists in patients with immune thrombocytopenia. [2021]The development of myeloid malignancies is a concern when administering thrombopoietin receptor (or the myeloproliferative leukemia virus proto-oncogene product, MPL) agonists. Progression from myelodysplastic syndrome (MDS) to acute myelogenous leukemia [AML, 9 (6.12%) AML patients among 147 MDS subjects] was reported in a clinical trial. However, only one (0.15%) case of AML among 653 immune thrombocytopenic purpura (ITP) subjects was reported. Our objective was to determine whether there is currently a safety signal in the FDA files termed Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) for AML in ITP patients who receive MPL agonists.
Updated results of the placebo-controlled, phase III JAKARTA trial of fedratinib in patients with intermediate-2 or high-risk myelofibrosis. [2022]Fedratinib, an oral Janus kinase-2 (JAK2) inhibitor, reduces splenomegaly and improves symptom burden in patients with myelofibrosis. Regulatory approval of fedratinib 400-mg daily was based on results of an updated analysis of the pivotal phase III, placebo-controlled JAKARTA trial in patients with JAK-inhibitor-naïve myelofibrosis. At week 24, spleen volume response rate was 47% and symptom response rate was 40% with fedratinib 400 mg, versus 1% and 9% respectively, with placebo. Common adverse events were diarrhoea, nausea, anaemia, and vomiting. No Wernicke encephalopathy occurred in patients receiving fedratinib 400 mg/day. These updated data support use of first-line fedratinib in patients with myelofibrosis.
Fedratinib in patients with myelofibrosis previously treated with ruxolitinib: An updated analysis of the JAKARTA2 study using stringent criteria for ruxolitinib failure. [2022]Fedratinib is an oral, selective Janus kinase 2 (JAK2) inhibitor. The phase II JAKARTA2 study assessed fedratinib in patients with intermediate- or high-risk myelofibrosis (MF) who were resistant or intolerant to prior ruxolitinib per investigator assessment. Patients received fedratinib 400 mg/day in 28-day cycles. The JAKARTA2 outcomes were initially reported using a last-observation-carried forward (LOCF) analysis in a "Per Protocol" population. This updated analysis of JAKARTA2 employs intention-to-treat analysis principles without LOCF for all treated patients (ITT Population; N = 97), and for a patient subgroup who met more stringent definitions of prior ruxolitinib failure (Stringent Criteria Cohort; n = 79). Median duration of prior ruxolitinib exposure was 10.7 months. The primary endpoint was spleen volume response rate (SVRR; ≥35% spleen volume decrease from baseline to end of cycle 6 [EOC6]). The SVRR was 31% in the ITT Population and 30% in the Stringent Criteria Cohort. Median duration of spleen volume response was not reached. Symptom response rate (≥50% reduction from baseline to EOC6 in total symptom score [TSS] on the modified Myelofibrosis Symptom Assessment Form [MFSAF]) was 27%. Grade 3-4 anemia and thrombocytopenia rates were 38% and 22%, respectively. Patients with advanced MF substantially pretreated with ruxolitinib attained robust spleen responses and reduced symptom burden with fedratinib.