Evidence map›Paper›PMID 38968138›Full record

ArticleBlood2024

A phase 1 clinical trial of NKTR-255 with CD19-22 CAR T-cell therapy for refractory B-cell acute lymphoblastic leukemia.

Hrishikesh Srinagesh, Clayton Jackson, Parveen Shiraz, Nikeshan Jeyakumar, Mark Hamilton, Emily Egeler, Sharon Mavroukakis, Adam Kuo, Juancarlos Cancilla, Bita Sahaf and 26 more

Registry-linked trialAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Blood, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03233854 (Phase 1 Dose Escalation Study of CD19/CD22 Chimeric Antigen Receptor), which is not on this map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03233854 phase1active not recruitingnot on this map

Phase 1 Dose Escalation Study of CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells With or Without NKTR-255 in Adults With Recurrent or Refractory B Cell Malignancies

TypeinterventionalSponsorStanford UniversityRan2017 to 2035Enrolled56ConditionsB Acute Lymphoblastic Leukemia, CD19 Positive, Minimal Residual Disease, Philadelphia Chromosome PositiveArmsChimeric Antigen Receptor T-Cell Therapy, Cyclophosphamide, Fludarabine Phosphate, Laboratory Biomarker Analysis, Questionnaire Administration
3 · Its place in the literature

Who cites it

19 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

36 authors.

Hrishikesh SrinageshDivision of Hematology, Stanford University, Stanford, CA.ORCID 0000-0001-9786-3010
Clayton JacksonDivision of Hematology/Oncology, UT Southwestern, Dallas, TX.
Parveen ShirazDivision of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA.ORCID 0000-0002-6721-0358
Nikeshan JeyakumarDivision of Hematology, Stanford University, Stanford, CA.ORCID 0000-0001-9979-4434
Mark HamiltonDivision of Hematology, Stanford University, Stanford, CA.
Emily EgelerCenter for Cancer Cell Therapy, Stanford University, Stanford, CA.
Sharon MavroukakisCenter for Cancer Cell Therapy, Stanford University, Stanford, CA.
Adam KuoCenter for Cancer Cell Therapy, Stanford University, Stanford, CA.ORCID 0000-0001-9797-0043
Juancarlos CancillaCenter for Cancer Cell Therapy, Stanford University, Stanford, CA.
Bita SahafCenter for Cancer Cell Therapy, Stanford University, Stanford, CA.
Neha AgarwalDivision of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA.
Alyssa KanegaiDivision of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA.
Anne Marijn KramerDivision of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA.ORCID 0000-0001-5239-7343
Sally AraiDivision of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA.ORCID 0000-0003-1993-4172
Sushma BharadwajDivision of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA.
Saurabh DahiyaDivision of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA.
Hitomi HosoyaDivision of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA.
Laura JohnstonDivision of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA.
Vanessa KennedyDivision of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA.
Michaela LiedtkeDivision of Hematology, Stanford University, Stanford, CA.ORCID 0000-0001-8945-5850
Robert LowskyDivision of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA.
Lekha MikkilineniDivision of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA.
Robert NegrinDivision of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA.
Andrew RezvaniDivision of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA.
Surbhi SidanaDivision of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA.ORCID 0000-0003-3288-7614
Judith ShizuruDivision of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA.
Melody SmithDivision of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA.ORCID 0000-0002-2702-0381
Wen-Kai WengDivision of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA.
Steven FeldmanCenter for Cancer Cell Therapy, Stanford University, Stanford, CA.ORCID 0000-0003-2098-3860
Matthew J FrankDivision of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA.
Zachary LeeNektar Therapeutics, San Francisco, CA.
Mary TagliaferriNektar Therapeutics, San Francisco, CA.
A Mario MarcondesNektar Therapeutics, San Francisco, CA.
David MiklosDivision of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA.ORCID 0000-0003-0717-4305
Crystal MackallCenter for Cancer Cell Therapy, Stanford University, Stanford, CA.ORCID 0000-0003-0359-9023
Lori MufflyDivision of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA.ORCID 0000-0002-9887-6136

Funding

TUMOR SPECIFIC CYTOTOXIC T-LYMPHOCYTES IN BONE MARROW TRANSPLANTATIONP01CA049605 · NCI · STANFORD UNIVERSITY · PI David B. Miklos · 1989 to 2026
$73.3M
Translational Oncology Research Program (Project-005)P30CA124435 · NCI · STANFORD UNIVERSITY · PI Vittorio Sebastiano · 2007 to 2026
$71.4M
NCI NIH HHS P01 CA049605NCI NIH HHS P30 CA124435
6 · The paper itself

Abstract

abstractAlthough chimeric antigen receptor (CAR) T-cell (CAR-T) therapy has revolutionized the treatment of B-cell malignancies, many patients relapse and therefore strategies to improve antitumor immunity are needed. We previously designed a novel autologous bispecific CAR targeting CD19 and CD22 (CAR19-22), which was well tolerated and associated with high response rates but relapse was common. Interleukin-15 (IL15) induces proliferation of diverse immune cells and can augment lymphocyte trafficking. Here, we report the results of a phase 1 clinical trial of the first combination of a novel recombinant polymer-conjugated IL15 receptor agonist (NKTR-255), with CAR19-22, in adults with relapsed/refractory B-cell acute lymphoblastic leukemia. Eleven patients were enrolled, 9 of whom successfully received CAR19-22 followed by NKTR-255. There were no dose-limiting toxicities, with transient fever and myelosuppression as the most common possibly related toxicities. We observed favorable efficacy with 8 of 9 patients (89%) achieving measurable residual disease-negative remission. At 12 months, progression-free survival for NKTR-255 was double that of historical controls (67% vs 38%). We performed correlative analyses to investigate the effects of IL15 receptor agonism. Cytokine profiling showed significant increases in IL15 and the chemokines CXCL9 and CXCL10. The increase in chemokines was associated with decreases in absolute lymphocyte counts and CD8+ CAR T cells in the blood and 10-fold increases in cerebrospinal fluid CAR-T cells, suggesting lymphocyte trafficking to tissue. Combining NKTR-255 with CAR19-22 was safe, feasible, and associated with high rates of durable responses. This trial was registered at www.clinicaltrials.gov as #NCT03233854.

Indexed as

Antigens, CD19Immunotherapy, AdoptiveReceptors, Chimeric AntigenAdultAgedFemaleHumansInterleukin-15MaleMiddle AgedPrecursor B-Cell Lymphoblastic Leukemia-LymphomaSialic Acid Binding Ig-like Lectin 2Young AdultAntigens, CD19CD19 molecule, humanInterleukin-15Receptors, Chimeric AntigenSialic Acid Binding Ig-like Lectin 2

Identifiers

PMID38968138
PMCPMC11522888

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.