B Acute Lymphoblastic LeukemiaPhase 1NCT03233854
CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells With or Without NKTR-255 in Adults With Recurrent or Refractory B Cell Malignancies
A Phase 1 study testing Chimeric Antigen Receptor T-Cell Therapy, Cyclophosphamide and Fludarabine Phosphate in people with B Acute Lymphoblastic Leukemia and CD19 Positive, run by Stanford University at 1 site in United States.
Trial summary
This phase I trial studies the side effects of CD19/CD22 chimeric antigen receptor (CAR) T cells when given together with chemotherapy and NKTR-255, and to see how well they work in treating patients with CD19 positive B acute lymphoblastic leukemia that has come back or does not respond to treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- B Acute Lymphoblastic Leukemia, CD19 Positive, Minimal Residual Disease
- What is being tested?
- Chimeric Antigen Receptor T-Cell Therapy, Cyclophosphamide and Fludarabine Phosphate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2017to 1 Sep 2035
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- History of other malignancy, unless disease free for at least 3 years. At the discretion of the Principal Investigator, subjects in remission for 1-2 years prior to enrollment may be deemed eligible after considering the nature of other malignancy, likelihood of recurrence during one year following CAR therapy, and impact of prior treatment on risk of CD19/CD22-CAR T cells. Subjects in remission <1 year are not eligible.
- Exception: Nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) is eligible.
- Hormonal therapy in subjects in remission >1 year will be allowed.
- Presence of fungal, bacterial, viral, or other infection that is uncontrolled. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
- Known history of infection with any of the following:
- HIV
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- Hepatitis B (HBsAg positive)
- Hepatitis C virus (anti-HCV positive) A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing.
- Presence of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement that in the judgment of the investigator may impair the ability to evaluate neurotoxicity.
- History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
- Any medical condition that in the judgement of the investigator is likely to interfere with assessment of safety or efficacy of study treatment
- History of severe immediate hypersensitivity reaction to any of the agents used in this study
- Women who are pregnant or breastfeeding
- In the investigator's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.
- Previous treatment with interleukin-2 or interleukin-15.
- Confirmed diagnosis of relapsed/refractory biphenotypic BT cell ALL
- Primary immunodeficiency or history of autoimmune disease (e.g. Crohns, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University, School of Medicine
Palo Alto, California, 94304
About this study
Official title: 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
This phase I trial studies the side effects of CD19/CD22 chimeric antigen receptor (CAR) T cells when given together with chemotherapy and NKTR-255, and to see how well they work in treating patients with CD19 positive B acute lymphoblastic leukemia that has come back or does not respond to treatment. A CAR is a genetically-engineered receptor made so that immune cells (T cells) can attack cancer cells by recognizing and responding to the CD19/CD22 proteins. These proteins are commonly found on diffuse large B-cell lymphoma and B acute lymphoblastic leukemia. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine phosphate, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. NKTR-255 is an investigational IL-15 receptor agonist designed to boost the immune system's natural ability to fight cancer. Giving CD19/CD22-CAR T cells and chemotherapy in combination with NKTR-255 may work better in treating patients with diffuse large B-cell lymphoma or B acute lymphoblastic leukemia.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the feasibility of producing CD19/CD22 CAR T cells meeting the established release criteria.
II. Assess the safety of administering escalating doses of autologous CD19/CD22 CAR T cells that meet established release specifications in adults with B cell hematologic malignancies following a cyclophosphamide/fludarabine conditioning regimen.
III. Assess the safety and feasibility of administering repeated doses of NKTR-255 intravenously after CD19/CD22-CAR T cell infusions in adults with ALL using a dose escalation design.
IV. Determine the recommended phase 2 dose (RP2D) of NKTR-255 when administered following CD19/CD22-CAR T cell infusion in adults with ALL
SECONDARY OBJECTIVES:
- Evaluate the ability of CD19/CD22 CAR T cells to mediate clinical activity in adults with DLBCL and adults with ALL.
II. Characterize the pharmacokinetics (PK) of NKTR-255 when administered post CD19/CD22 CAR T cell infusion.
III. Explore the rate of relapse, progression free survival (PFS) and overall survival (OS) in subjects receiving CD19/CD22 CAR T cells, followed by up to 6 cycles of NKTR-255
- Conditions
- B Acute Lymphoblastic Leukemia, CD19 Positive, Minimal Residual Disease, Philadelphia Chromosome Positive
- Being tested
- Chimeric Antigen Receptor T-Cell Therapy, Cyclophosphamide, Fludarabine Phosphate, Laboratory Biomarker Analysis, Questionnaire Administration
- Medical subject headings
- Burkitt Lymphoma, Neoplasm, Residual
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chimeric Antigen Receptor T-Cell TherapyBiological
Also called CAR T-cell therapy
Given CD19/CD22 CAR T cells IV
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida
Given IV
Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
Questionnaire AdministrationOther
Ancillary studies
NKTR-255Drug
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (CD19/CD22 CAR T cells, chemotherapy, NKTR-255) | Experimental | Patients receive cyclophosphamide IV over 60 minutes and fludarabine phosphate IV over 30 minutes on days -5 to -3. Patients then receive CD19/CD22 CAR T cells IV over 10-20 minutes on day 0. On Day 14 after CAR-T, eligible patients will be given NKTR-255 IV over 30 minutes, and it will be repeated every 28 days for up to 6 cycles. Patients that benefited from the first dose of CD19/CD22 CAR T cells, had no unacceptable side effects, and have enough cells left over may receive 2 or 3 additional doses of CD19/CD22 CAR T cells. Receives: Biological: Chimeric Antigen Receptor T-Cell Therapy; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration; Drug: NKTR-255 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of dose limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD19/CD22 chimeric antigen receptor (CAR) T cells
Safety data will be analyzed per standard methods and interpreted descriptively for each dose cohort. Safety data will be summarized for each dose cohort separately and for all dose cohorts combined. Adverse events will be assessed using the CTCAE version 4.03 for type and severity of event. Serious Adverse Events will be summarized for each dose cohort and for all dose cohorts combined. Reasons for discontinuation of study therapy will be tabulated.
Measured: Up to 28 days
Maximum tolerated dose of CD19/CD22 chimeric antigen receptor (CAR) T cells defined as the dose level immediately below the level at which the enrollment is stopped due to a dose limiting toxicity
Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Measured: Up to 28 days
Rate of successful manufacture and expansion of the CD19/CD22 chimeric antigen receptor (CAR) T cells to satisfy the targeted dose level and meet the required release specifications outlined in the Certificate of Analysis
In addition to aiming to evaluate up to 6 subjects at a given dose level with respect to toxicity, the number of subjects which can successfully manufacture the targeted dose number will be determined.
Measured: Up to 15 years
Secondary outcomes (3)
Overall survival
Will be assessed by dose cohort.
Measured: From the start of the preparative regimen until death, assessed for up to 15 years
Progression free survival
Will be assessed by dose cohort.
Measured: From the start of the preparative regimen until the documentation of disease progression or death due to any cause, whichever occurs first, assessed for up to 15 years
The ability to achieve a clinical response after administration of CD19/CD22 chimeric antigen receptor (CAR) T cells
Will be assessed by the Response Criteria for Lymphoma and the Response Criteria for Acute Lymphoblastic Leukemia.
Measured: Up to 15 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2017
- Study start1 Sep 2017
- Primary completion20 Jun 2023
- Study completion1 Sep 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for B Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- California Institute for Regenerative Medicine (CIRM)
- Responsible party
- Sponsor
- Investigators
- Lori Muffly, MD, MS, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03233854
- Sponsor's protocol ID
- IRB-41382
- Other IDs
- NCI-2017-01291
- Status last verified
- Nov 2025
- First submitted
- 26 Jul 2017
- Last updated
- 18 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Srinagesh H, Jackson C, Shiraz P, Jeyakumar N, Hamilton M, Egeler E, Mavroukakis S, Kuo A, Cancilla J, Sahaf B, Agarwal N, Kanegai A, Kramer AM, Arai S, Bharadwaj S, Dahiya S, Hosoya H, Johnston L, Kennedy V, Liedtke M, Lowsky R, Mikkilineni L, Negrin R, Rezvani A, Sidana S, Shizuru J, Smith M, Weng WK, Feldman S, Frank MJ, Lee Z, Tagliaferri M, Marcondes AM, Miklos D, Mackall C, Muffly L. A phase 1 clinical trial of NKTR-255 with CD19-22 CAR T-cell therapy for refractory B-cell acute lymphoblastic leukemia. Blood. 2024 Oct 17;144(16):1689-1698. doi: 10.1182/blood.2024024952.
PubMed 38968138Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
PubMed 34515338Spiegel JY, Patel S, Muffly L, Hossain NM, Oak J, Baird JH, Frank MJ, Shiraz P, Sahaf B, Craig J, Iglesias M, Younes S, Natkunam Y, Ozawa MG, Yang E, Tamaresis J, Chinnasamy H, Ehlinger Z, Reynolds W, Lynn R, Rotiroti MC, Gkitsas N, Arai S, Johnston L, Lowsky R, Majzner RG, Meyer E, Negrin RS, Rezvani AR, Sidana S, Shizuru J, Weng WK, Mullins C, Jacob A, Kirsch I, Bazzano M, Zhou J, Mackay S, Bornheimer SJ, Schultz L, Ramakrishna S, Davis KL, Kong KA, Shah NN, Qin H, Fry T, Feldman S, Mackall CL, Miklos DB. CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial. Nat Med. 2021 Aug;27(8):1419-1431. doi: 10.1038/s41591-021-01436-0. Epub 2021 Jul 26.
PubMed 34312556