AzTrials
AzTrials

Recurrent Adult Acute Lymphoblastic LeukemiaPhase 1NCT03103971

huJCAR014 CAR-T Cells in Treating Adult Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma or Acute Lymphoblastic Leukemia

A Phase 1 study testing Autologous Human Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ T-lymphocytes, Cyclophosphamide and Fludarabine in people with Recurrent Adult Acute Lymphoblastic Leukemia and Recurrent B-Cell Non-Hodgkin Lymphoma, run by Fred Hutchinson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This phase I trial studies the side effects of huJCAR014 in treating patients with relapsed or refractory B-cell non-Hodgkin lymphoma or acute lymphoblastic leukemia. huJCAR014 CAR-T cells are made in the laboratory by genetically modifying a patient's T cells and may specifically kill cancer cells that have a… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Autologous Human Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ T-lymphocytes, Cyclophosphamide and Fludarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
55 participants
Where
1 siteUnited States
Study dates
3 Nov 2017to 23 Mar 2024
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Male or female >= 18 years of age at the time of screening consent
  • Diagnosis of R/R B-cell NHL or ALL as defined below:
  • Relapsed or refractory B-cell NHL meeting all of the following criteria:
  • Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS); high grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements; LBCL transformed from any indolent histology; or primary mediastinal B-cell lymphoma (PMBCL)
  • Prior treatment with an anthracycline and rituximab or another CD20-targeted agent (unless the disease is CD20-negative); transformed DLBCL (tDLBCL) must have failed treatment for DLBCL
  • At least one of the following:
Show all 36Show fewer
  • Refractory disease after frontline chemo-immunotherapy
  • Not eligible for autologous hematopoietic stem cell transplant (auto-HSCT)
  • Relapsed or refractory disease after at least 2 lines of therapy or after auto-HSCT
  • Relapsed or refractory disease after allogeneic hematopoietic stem cell transplant (allo-HSCT)
  • Relapsed or refractory B-cell ALL (patients with Burkitt's lymphoma/leukemia are not eligible)
  • All B-ALL patients must have detectable disease by morphology, flow cytometry, cytogenetic analysis (e.g. polymerase chain reaction [PCR], fluorescence in situ hybridization [FISH], karyotyping) or imaging (e.g. positron emission tomography [PET]/computed tomography [CT]) or a high likelihood of active disease
  • Refractory: failure to achieve complete response (CR) (minimal residual disease [MRD]-negative) at the end of induction
  • Relapsed: recurrence of disease after achieving CR
  • Evidence of CD19 expression by immunohistochemistry or flow cytometry on any prior or current tumor specimen or high likelihood of CD19 expression based on disease histology
  • INCLUSION CRITERIA FOR LEUKAPHERESIS AND PRE-THERAPY EVALUATION
  • Screening evaluation appropriate for leukapheresis and T-cell collection
  • Adequate vascular access available or planned for leukapheresis procedure (either peripheral line or surgically placed line)
  • Documentation of CD19 expression on any prior or current tumor biopsy; patients who have received previous CD19-targeted therapy must have CD19-positive disease confirmed on a biopsy since completing the prior CD19-targeted therapy
  • Internal review of histology
  • Stage 2; cohort 2B (CAR-exposed) only:
  • Relapsed disease after achieving CR at the discretion of the principal investigator (PI) or designee, after prior CD19-targeted non-huJCAR014 CAR T-cell therapy. Patients who were in CR prior to the CD19-targeted non-huJCAR014 CAR T-cell therapy may be considered eligible at the discretion of the PI or designee. OR
  • Persistent disease after achieving PR at the discretion of the PI or designee, after prior CD19-targeted non-huJCAR014 CAR T-cell therapy. Patients who are less than 3 months from prior CD19-targeted non-huJCAR014 CAR T-cell therapy must have persistent disease on biopsy or imaging (e.g. PET-CT or CT) evidence of disease progression
  • INCLUSION CRITERIA FOR LYMPHODEPLETING CHEMOTHERAPY AND huJCAR014 TREATMENT
  • Successful collection of T cells for huJCAR014 manufacturing
  • Detectable disease by imaging (for example PET +/- CT, magnetic resonance imaging [MRI]) and/or pathology evaluation
  • Karnofsky performance status >= 60%
  • Assessed by the investigator to have adequate bone marrow function to receive lymphodepleting conditioning chemotherapy
  • Serum creatinine =< 1.5 x age-adjusted upper limit of normal (ULN) or calculated creatinine clearance (Cockcroft and Gault) > 30 mL/min/1.73 m^2
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 5 x ULN and total bilirubin < 2.0 mg/dL unless due to malignancy or Gilbert's syndrome in the opinion of the PI or designee
  • Common Terminology Criteria for Adverse Events (CTCAE) grade =< 1 dyspnea and oxygen saturation (SaO2) >= 92% on room air
  • Left ventricular ejection fraction (LVEF) >= 40% as assessed by echocardiogram (ECHO) or multiple uptake gated acquisition (MUGA) scan performed within 1 month before starting lymphodepleting chemotherapy
  • Women of childbearing potential (defined as all women physiologically capable of becoming pregnant) must agree to both of the following:
  • Use highly effective methods of contraception for at least 6 months after the last dose of huJCAR014, and
  • Have a negative serum pregnancy test performed within 28 days before starting lymphodepleting chemotherapy
  • Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method for at least 6 months after the last dose of huJCAR014

Who cannot join

  • For patients in stage 1 only, prior treatment with any CD19 CAR T-cell therapy is excluded
  • Known active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection
  • Pregnant or breastfeeding women
  • Any known contraindication to leukapheresis
  • Any known and irreversible contraindication to huJCAR014 therapy
  • Medical, psychological, familial, sociological, or geographical condition that does not permit compliance with the protocol as judged by the PI or designee, or unwillingness or inability to follow protocol procedures
Show all 23Show fewer
  • EXCLUSION CRITERIA FOR LEUKAPHERESIS AND PRE-THERAPY EVALUATION
  • History or presence of clinically relevant central nervous system (CNS) pathology that, in the opinion of the PI or designee, is a contraindication to lymphodepleting chemotherapy or huJCAR014 infusion
  • History of another primary malignancy that has not been in remission for at least 2 years with the following exceptions: nonmelanoma skin cancer, curatively treated localized prostate cancer, cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Pap smear, or other malignancy considered by the investigator to have a low risk of relapse or progression
  • Active autoimmune disease requiring immunosuppressive therapy, unless considered by the PI or designee to be eligible
  • Presence of active acute or chronic graft versus host disease (GVHD)
  • Use of any of the following:
  • Cytotoxic or lymphotoxic agents (including prednisone > 5 mg/day or equivalent corticosteroid) within 1 week prior to leukapheresis; physiologic corticosteroid replacement, and topical or inhaled corticosteroids are not excluded
  • GVHD therapies within 4 weeks prior to leukapheresis (e.g., calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as anti-TNF, anti-IL-6, or anti-IL-6R)
  • Experimental agents within 4 weeks prior to leukapheresis unless progression is documented on therapy and at least 3 half-lives have elapsed prior to leukapheresis
  • Radiation encompassing all sites of known tumor within 6 weeks prior to leukapheresis, unless there is evidence of active disease after radiation by imaging, biopsy or clinical evaluation
  • Allo-HSCT within 60 days prior to leukapheresis or donor lymphocyte infusion (DLI) within 6 weeks prior to leukapheresis
  • Treatment with cladribine within 3 months prior to leukapheresis
  • Treatment with alemtuzumab within 3 months prior to leukapheresis
  • EXCLUSION CRITERIA FOR LYMPHODEPLETING CHEMOTHERAPY AND huJCAR014 TREATMENT
  • Uncontrolled and serious infection
  • Presence of active acute or chronic GVHD
  • DLI within 6 weeks prior to lymphodepletion chemotherapy

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Two-Stage Phase 1 Open-Label Study of huJCAR014, CD19-Targeted Chimeric Antigen Receptor (CAR)-Modified T Cells Bearing a Human Binding Domain, in Adult Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma and Acute Lymphocytic Leukemia

This phase I trial studies the side effects of huJCAR014 in treating patients with relapsed or refractory B-cell non-Hodgkin lymphoma or acute lymphoblastic leukemia. huJCAR014 CAR-T cells are made in the laboratory by genetically modifying a patient's T cells and may specifically kill cancer cells that have a molecule CD19 on their surfaces.

In Stage 1, dose-finding studies will be conducted in 3 cohorts:

Read more
  1. Aggressive B cell NHL
  2. Low burden ALL
  3. High burden ALL

In Stage 2, studies may be conducted in one or more cohorts to collect further safety, PK, and efficacy information at the huJCAR014 dose level(s) selected in Stage 1 for the applicable cohort(s). There are two separate cohorts for stage 2:

  1. Cohort 2A, CAR-naïve (n=10): patients who have never received CD19 CAR-T cell therapy.
  2. Cohort 2B, CAR-exposed (n=27): patients who have previously failed CD19 CAR-T cell therapy.
Read the detailed description

OUTLINE: This is a dose-escalation study of huJCAR014.

Patients undergo leukapheresis. Beginning 1-2 weeks after leukapheresis, patients undergo lymphodepleting chemotherapy comprising either cyclophosphamide intravenously (IV) daily for 1 day and fludarabine IV daily for 3 days or cyclophosphamide and fludarabine IV daily for 3 days. Alternative lymphodepleting chemotherapy regimens maybe used if patient's clinical situation or other logistical factors dictate otherwise. Within 36-96 hours after completion of lymphodepleting chemotherapy, patients receive huJCAR014 IV over 20-30 minutes on day 0.

After completion of study treatment, patients are followed up every 30 days for the first 3 months, every 3 months for up to 12 months, and then yearly for 15 years.

Being tested
Autologous Human Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ T-lymphocytes, Cyclophosphamide, Fludarabine, Laboratory Biomarker Analysis, Leukapheresis
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Burkitt Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Autologous Human Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ T-lymphocytesBiological

    Also called Anti-CD19-CAR Genetically Engineered Autologous T Lymphocytes huJCAR014, Anti-CD19-CAR Genetically Engineered Autologous T-lymphocytes huJCAR014, Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ T-lymphocytes, huJCAR014

    Given IV

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • LeukapheresisProcedure or surgery

    Also called Leukocytopheresis, Therapeutic Leukopheresis

    Undergo leukapheresis

  • Pharmacological StudyOther

    Correlative studies

Study groups in NCT03103971
Study groupRoleWhat they receive
Treatment (leukapheresis, chemotherapy, huJCAR014)ExperimentalPatients undergo leukapheresis. Beginning 14-16 days after leukapheresis, patients undergo lymphodepleting chemotherapy comprising either cyclophosphamide IV daily for 1 day and fludarabine IV daily for 3 days or cyclophosphamide and fludarabine IV daily for 3 days. Within 36-96 hours after completion of lymphodepleting chemotherapy, patients receive huJCAR014 IV over 20-30 minutes on day 0.
Receives: Biological: Autologous Human Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ T-lymphocytes; Drug: Cyclophosphamide; Drug: Fludarabine; Other: Laboratory Biomarker Analysis; Procedure: Leukapheresis; Other: Pharmacological Study

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of toxicity

    Will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. All adverse events (AEs) will be listed and summarized. Summaries of laboratory data will include, at a minimum, treatment-emergent laboratory abnormalities. Summaries of AEs and laboratory abnormalities will be based on the All Treated analysis set.

    Measured: Up to 30 days after the final dose of study therapy

  2. Dose-limiting toxicity (DLT) rates

    Observed DLT rates will be summarized based on the DLT-Evaluable analysis set. Final DLT rates at each dose level will be estimated by isotonic regression.

    Measured: Up to 28 days

  3. Maximum concentration (Cmax) of autologous human anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ T-lymphocytes (huJCAR014) cells in blood

    huJCAR014 will be measured in blood using quantitative polymerase chain reaction (PCR) (qPCR) and flow cytometry over 28 days after huJCAR014 infusion. Cmax is the peak concentration of huJCAR014 cells in blood in the first 28 days after infusion.

    Measured: Up to 28 days

  4. Time to maximum concentration (Tmax), of huJCAR014 cells in blood

    huJCAR014 will be measured in blood using quantitative PCR (qPCR) and flow cytometry over 28 days after huJCAR014 infusion. Tmax is the time to reach the maximum concentration of huJCAR014 cells in blood in the first 28 days.

    Measured: Up to 28 days

  5. Area under the curve of huJCAR014 cells in blood

    huJCAR014 will be measured in blood using quantitative PCR (qPCR) and flow cytometry over 28 days after huJCAR014 infusion. AUC is the calculated area under the curve of huJCAR014 concentrations in blood by time after infusion through 28 days.

    Measured: Up to 28 days

  6. Presence of huJCAR014 cells in bone marrow

    The persistence of huJCAR014 in the bone marrow at 28 days will be assessed, based on both a qPCR assay and flow cytometry.

    Measured: Up to 28 days

Secondary outcomes (7)

  1. Complete response (CR) rate

    Will be summarized along with the 2-sided 95% exact Clopper-Pearson confidence intervals based on the efficacy-evaluable (EE) analysis sets. In addition, CR rate will be presented based on the all-treated analysis set

    Measured: Up to 15 years

  2. Partial response (PR) rate

    Will be summarized along with the 2-sided 95% exact Clopper-Pearson confidence intervals based on the EE analysis sets.

    Measured: Up to 15 years

  3. Objective response rate (ORR)

    Will be defined as the proportion of patients with a best response of either CR or PR. Will be summarized along with the 2-sided 95% exact Clopper-Pearson confidence intervals based on the EE analysis sets. In addition, ORR will be presented based on the All-Treated analysis set.

    Measured: Up to 15 years

  4. Duration of response (DOR)

    Will be defined as the time from date of first response to relapse/progression or death. Kaplan-Meier (KM) methodology will be used to analyze DOR.

    Measured: Up to 15 years

  5. Progression-free survival (PFS)

    KM methodology will be used to analyze PFS.

    Measured: From date of first huJCAR014 infusion to progressive disease or death, assessed up to 15 years

  6. Event-free survival (EFS)

    KM methodology will be used to analyze EFS.

    Measured: From the date of the first huJCAR014 infusion to death from any cause, relapse, or treatment failure, whichever occurs first, assessed up to 15 years

  7. Overall survival (OS)

    KM methodology will be used to analyze OS.

    Measured: From date of first huJCAR014 infusion to death, assessed 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.

  1. First posted7 Apr 2017
  2. Study start3 Nov 2017
  3. Primary completion23 Mar 2023
  4. Study completion23 Mar 2024

Why it stopped: Terminated due to slow enrollment and end of funding

Resources

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
55 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03103971
Sponsor's protocol ID
9364
Other IDs
NCI-2017-00421, 9364, RG9217000
Status last verified
Apr 2024
First submitted
27 Mar 2017
Last updated
10 Apr 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Gauthier J, Liang EC, Huang JJ, Kimble EL, Hirayama AV, Fiorenza S, Voutsinas JM, Wu QV, Jaeger-Ruckstuhl CA, Pender BS, Kirchmeier DR, Torkelson A, Braathen K, Basom R, Shadman M, Kopmar NE, Cassaday RD, Riddell SR, Maloney DG, Turtle CJ. Phase 1 study of CD19 CAR T-cell therapy harboring a fully human scFv in CAR-naive adult patients with B-ALL. Blood Adv. 2025 Apr 22;9(8):1861-1872. doi: 10.1182/bloodadvances.2024015314.

    PubMed 39820359

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Autologous Human Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ T-lymphocytes, Cyclophosphamide and Fludarabine in people with Recurrent Adult Acute Lymphoblastic Leukemia and Recurrent B-Cell Non-Hodgkin Lymphoma, run by Fred Hutchinson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 36 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 10 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Terminated due to slow enrollment and end of funding). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of toxicity (time frame: Up to 30 days after the final dose of study therapy). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03103971, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in