NCT02906371

Brief 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 tumor burden following redirected autologous T cells transduced with the anti-CD19 lentiviral vector (CART19/CTL019).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
80

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Aug 2016

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2016

Completed
28 days until next milestone

First Submitted

Initial submission to the registry

August 29, 2016

Completed
22 days until next milestone

First Posted

Study publicly available on registry

September 20, 2016

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 11, 2020

Completed
1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2021

Completed
Last Updated

July 2, 2021

Status Verified

June 1, 2021

Enrollment Period

3.6 years

First QC Date

August 29, 2016

Last Update Submit

June 30, 2021

Conditions

Lymphoblastic Leukemia, Acute, Childhood

Outcome Measures

Primary Outcomes (1)

  • the frequency of grade 4 CRS

    Frequency of CRS grade 4

    from day 1 to 1 year

Secondary Outcomes (1)

  • tumor response

    day 28

Other Outcomes (4)

  • CART19 cellular kinetics

    from day -1 to year 1

  • Number of days in ICU

    from day 0 through year one.

  • Frequency of major medical interventions

    from day 0 through year one.

  • +1 more other outcomes

Study Arms (2)

Tocilizumab high tumor burden

ACTIVE COMPARATOR

This 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).

Drug: TocilizumabBiological: CART 19

Tocilizumab low tumor burden

ACTIVE COMPARATOR

This 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).

Drug: TocilizumabBiological: CART 19

Interventions

TocilizumabDRUG

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.

Also known as: high tumor burden
Tocilizumab high tumor burden
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.

Tocilizumab high tumor burdenTocilizumab low tumor burden

Eligibility Criteria

Age1 Year - 24 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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:
  • nd 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
  • 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:
  • +22 more criteria

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

  • 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.

    PMID: 33417474DERIVED

Related Links

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Leukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Study Officials

  • Stephan A Grupp, MD,PhD

    Children's Hospital of Philadelphia

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 29, 2016

First Posted

September 20, 2016

Study Start

August 1, 2016

Primary Completion

March 11, 2020

Study Completion

June 30, 2021

Last Updated

July 2, 2021

Record last verified: 2021-06

Locations

US(1)