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Lymphoblastic Leukemia, Acute, ChildhoodPhase 1NCT02906371

Study of the Tocilizumab Optimization Timing for CART19 Associated Cytokine Release Syndrome

A Phase 1 study testing Tocilizumab and CART 19 in people with Lymphoblastic Leukemia, Acute, Childhood, run by University of Pennsylvania at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a two cohort, open-label, pilot study to describe the efficacy of administration timing of tocilizumab on CART19 (CTL019) associated cytokine release syndrome safety events in pediatric patients with CD19 expressing relapsed and refractory B-cell acute lymphoblastic leukemia with high versus low pre-infusion… Read more about this study

Who is it for?
Ages 1 year to 24 years
Conditions the study is for
Lymphoblastic Leukemia, Acute, Childhood
What is being tested?
Tocilizumab and CART 19
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
1 siteUnited States
Study dates
Aug 2016to 30 Jun 2021
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 1 year to 24 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Signed informed consent form must be obtained prior to any study procedure. Labs, marrows or other procedures obtained during routine clinical care may be used for eligibility if obtained within the protocol required windows.
  • Relapsed or refractory B-cell ALL:
  • 2nd or greater marrow relapse OR
  • CNS relapse OR
  • Any relapse after allogeneic hematopoietic stem cell (SCT) transplant and ≥ 4 months from SCT at enrollment OR
  • Any relapse after CAR-modified T cell therapy OR
Show all 37Show fewer
  • Refractory disease defined as having not achieved an MRD-negative CR after ≥ 2 chemotherapy regimens/cycles (1 cycle for relapsed patients) OR
  • Patients with Ph+ ALL are eligible if they are intolerant to or have failed tyrosine kinase inhibitor therapy OR
  • Ineligible for allogeneic SCT because of:
  • Comorbid disease
  • Other contraindications to allogeneic SCT conditioning regimen
  • Lack of suitable donor
  • Prior SCT
  • Declines allogeneic SCT as the therapeutic option after documented discussion, with expected outcomes, about the role of SCT with a bone marrow transplant (BMT) physician not part of the study team
  • Patients with B lymphoblastic lymphoma will be eligible if they meet one of the above criteria OR:
  • 2nd or greater relapse OR
  • Refractory disease defined as having not achieved CR with frontline therapy or after 1 cycle of reinduction therapy for relapsed patients
  • Patients with prior or current history of CNS3 disease will be eligible if CNS disease is responsive to therapy (at infusion, must meet criteria in Section 5.3)
  • Documentation of CD19 tumor expression in bone marrow, peripheral blood, CSF, or tumor tissue by flow cytometry at relapse (or a recent sample in the case of refractory disease). If the patient has received CD19-directed therapy (i.e. blinatumomab), then the flow cytometry should be obtained after this therapy to show CD19 expression.
  • Adequate organ function defined as:
  • A serum creatinine based on age/gender as follows:
  • Maximum Serum Creatinine (mg/dL)
  • Age Male Female
  • 1 to < 2 years 0.6 0.6
  • 2 to < 6 years 0.8 0.8
  • 6 to < 10 years 1.0 1.0
  • 10 to < 13 years 1.2 1.2
  • 13 to < 16 years 1.5 1.4
  • ≥ 16 years 1.7 1.4
  • ALT ≤500 U/L
  • Bilirubin ≤2.0 mg/dl
  • Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea, pulse oximetry > 92% on room air; DLCO ≥ 40% (corrected for anemia) if PFTs are clinically appropriate as determined by the treating investigator
  • Left Ventricular Shortening Fraction (LVSF) ≥ 28% or Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO, or adequate ventricular function documented by a scan or a cardiologist.
  • Evidence of disease by standard morphologic or MRD criteria. A clinical marrow or tissue biopsy showing disease may be performed at enrollment or within 12 weeks of enrollment. Presence of marrow disease not required for CNS disease or lymphoblastic lymphoma patients.
  • Age 1-29 years. Patients ages 24-29 years are eligible if their original leukemia diagnosis was prior to age 21.
  • Adequate performance status (Lansky or Karnofsky score ≥50).
  • Subjects of reproductive potential must agree to use acceptable birth control methods, as described in protocol Section 4.3.

Who cannot join

  • Active hepatitis B or active hepatitis C.
  • HIV Infection.
  • Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy.
  • 5. CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
  • 6. Pregnant or nursing (lactating) women. 8. Uncontrolled active infection.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: A Two Cohort Pilot Study of the Tocilizumab Optimization Timing for CART19 Associated Cytokine Release Syndrome (CRS) Management in Pediatric Patients With CD19 Expressing Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia (ALL)

This is a two cohort, open-label, pilot study to describe the efficacy of administration timing of tocilizumab on CART19 (CTL019) associated cytokine release syndrome safety events in pediatric patients with CD19 expressing relapsed and refractory B-cell acute lymphoblastic leukemia with high versus low pre-infusion tumor burden following redirected autologous T cells transduced with the anti-CD19 lentiviral vector (CART19/CTL019).

Read the detailed description

The duration of active protocol intervention is approximately 12-15 months from the screening visit. The protocol will require approximately 12-18 months to complete enrollment.Approximately 39 enrolled patients to reach at least 35 infused patients, with the ultimate goal of 15 patients in the high tumor burden cohort (Cohort A). Inclusion criteria are designed to include pediatric patients aged 1-24 years with CD19 expressing relapsed/refractory B-cell acute lymphoblastic leukemia (ALL).Tocilizumab will be given once to high disease burden patients, and then the patients will be managed for CRS as per the standard algorithm (including subsequent tocilizumab, if needed).

Two cohorts are defined based upon pre-infusion high versus low tumor burden; with the high tumor burden cohort (high risk of severe CRS) to receive earlier administration of tocilizumab for CRS management and the low tumor burden cohort (low risk of severe CRS) to receive standard timing of tocilizumab for CRS

Being tested
Tocilizumab, CART 19
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

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

  • TocilizumabDrug

    Also called high tumor burden

    Patients with ≥ 40% blasts in the bone marrow at pre-infusion will be enrolled in the early tocilizumab cohort and will follow early CRS treatment algorithm.

  • TocilizumabDrug

    Also called low tumor burden

    Patients with ˂ 40% blasts in the bone marrow at pre-infusion (~ Day -5 to -1) will follow the standard CRS Rx algorithm

  • CART 19Biological

    CART-19 cells transduced with a lentiviral vector to express either anti-CD19ζ scFv TCRζ:41BB, administered by i.v. injection using an intra-patient dose escalation approach: 10% on day 0, 30% on day 1 with a total dose goal of ~1.5 x107 - 5 x109 (~3x105 - 1x108/kg) T cells.

Study groups in NCT02906371
Study groupRoleWhat they receive
Tocilizumab high tumor burdenActive comparatorThis is a two cohort, open-label, pilot study to describe the efficacy of administration timing of tocilizumab on CART19 (CTL019) associated CRS safety events in pediatric patients with CD19 expressing relapsed and refractory B-cell acute lymphoblastic leukemia with high pre-infusion tumor burden following redirected autologous T cells transduced with the anti-CD19 lentiviral vector (CART19/CTL019).
Receives: Drug: Tocilizumab; Biological: CART 19
Tocilizumab low tumor burdenActive comparatorThis is a two cohort, open-label, pilot study to describe the efficacy of administration timing of tocilizumab on CART19 (CTL019) associated CRS safety events in pediatric patients with CD19 expressing relapsed and refractory B-cell acute lymphoblastic leukemia with low pre-infusion tumor burden following redirected autologous T cells transduced with the anti-CD19 lentiviral vector (CART19/CTL019).
Receives: Drug: Tocilizumab; Biological: CART 19

What is being measured

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

  1. the frequency of grade 4 CRS

    Frequency of CRS grade 4

    Measured: from day 1 to 1 year

Secondary outcomes (1)

  1. tumor response

    Frequency of CR with minimal residual disease negative bone marrow at day 28 and duration of remission

    Measured: day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Sep 2016 (estimated)
  2. Study startAug 2016
  3. Primary completion11 Mar 2020
  4. Study completion30 Jun 2021

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02906371
Sponsor's protocol ID
16CT022, 825445
Status last verified
Jun 2021
First submitted
29 Aug 2016
Last updated
2 Jul 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Kadauke S, Myers RM, Li Y, Aplenc R, Baniewicz D, Barrett DM, Barz Leahy A, Callahan C, Dolan JG, Fitzgerald JC, Gladney W, Lacey SF, Liu H, Maude SL, McGuire R, Motley LS, Teachey DT, Wertheim GB, Wray L, DiNofia AM, Grupp SA. Risk-Adapted Preemptive Tocilizumab to Prevent Severe Cytokine Release Syndrome After CTL019 for Pediatric B-Cell Acute Lymphoblastic Leukemia: A Prospective Clinical Trial. J Clin Oncol. 2021 Mar 10;39(8):920-930. doi: 10.1200/JCO.20.02477. Epub 2021 Jan 8.

    PubMed 33417474

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tocilizumab and CART 19 in people with Lymphoblastic Leukemia, Acute, Childhood, run by University of Pennsylvania 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 37 inclusion and 5 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: finished, as of the sponsor's last update on 2 Jul 2021. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

the frequency of grade 4 CRS (time frame: from day 1 to 1 year). 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 NCT02906371, 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 2 Jul 2021.

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