NCT02374333

Brief Summary

This is a pilot study to evaluate humanized CD19 redirected autologous T cells (or huCART19 cells) in patients with relapsed or refractory CD19+ leukemia and lymphoma that was previously treated with cell therapy. This study is targeting pediatric patients aged 1-24 years with CD19+ B cell malignancies with no available curative treatment options (such as autologous or allogeneic stem cell transplantation) who have a limited prognosis with currently available therapies and were previously treated with a B cell directed engineered cell therapy product.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
81

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Mar 2014

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

March 25, 2014

Completed
11 months until next milestone

First Submitted

Initial submission to the registry

February 23, 2015

Completed
4 days until next milestone

First Posted

Study publicly available on registry

February 27, 2015

Completed
6.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 2, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 2, 2021

Completed
Last Updated

September 23, 2021

Status Verified

September 1, 2021

Enrollment Period

7.4 years

First QC Date

February 23, 2015

Last Update Submit

September 22, 2021

Conditions

Acute Lymphocytic LeukemiaDiffuse Large Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

  • Occurrence of study related adverse events defined as NCI CTCAE 4.0 > grade 3 possibly, probably, or definitely related to study treatment.

    Study treatment until Week 24

Study Arms (1)

huCART19

EXPERIMENTAL

CART19 cells transduced with a lentiviral vector to express humanized anti-CD19 administered by IV injection

Biological: huCART19

Interventions

huCART19BIOLOGICAL
Also known as: huCTL019
huCART19

Eligibility Criteria

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

You may qualify if:

  • Male and female subjects with documented CD19+ B cell malignancies and no available curative treatment options (such as autologous or allogeneic SCT) who have limited prognosis (several months to \<2 year survival) with currently available therapies will be enrolled:
  • Eligible diseases: CD19+ leukemia or lymphoma. In general, these will be patients with:
  • ALL without curative options for therapy, including those not eligible for allogeneic SCT. Patient may be in any complete response, or patient may have active disease but responding or stable after most recent therapy.The intent is not to enroll patients with no degree of disease control or rapidly increasing disease burden between enrollment and cell infusion.
  • Diffuse large cell lymphoma or other high-grade NHL, previously identified as CD19+ including residual disease after primary therapy and not eligible for autologous SCT; relapsed after prior autologous SCT; beyond 1st CR with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT.
  • Patients previously treated with B cell directed engineered cell therapy are eligible if they meet one of the following criteria:
  • partial response or no response to prior cell therapy
  • relapsed after prior cell therapy
  • demonstrated B cell recovery suggesting loss of engineered cells.
  • Documented CD19 expression (after previous B cell directed cell therapy, if applicable)
  • Age 1 to 24 years
  • Expected survival \> 12 weeks
  • Creatinine \< 2.5 mg/dl and less than 2.5x normal for age
  • Bilirubin \<2.0 mg/dl
  • Adequate pulmonary function defined as \< Grade 3 hypoxia
  • Adequate cardiac function defined as LVSF ≥ 28% confirmed by ECHO
  • +6 more criteria

You may not qualify if:

  • Pregnant or lactating women. The safety of this therapy on unborn children is not known. Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion.
  • Uncontrolled active infection.
  • Active hepatitis B or hepatitis C infection.
  • Concurrent use of systemic steroids at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well.
  • Presence of grade 2-4 acute or extensive chronic GVHD.
  • Under treatment for GVHD.
  • CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity
  • Any uncontrolled active medical disorder that would preclude participation as outlined.
  • HIV 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 (2)

  • Ernst 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.

    PMID: 34515338DERIVED

  • Myers RM, Li Y, Barz Leahy A, Barrett DM, Teachey DT, Callahan C, Fasano CC, Rheingold SR, DiNofia A, Wray L, Aplenc R, Baniewicz D, Liu H, Shaw PA, Pequignot E, Getz KD, Brogdon JL, Fesnak AD, Siegel DL, Davis MM, Bartoszek C, Lacey SF, Hexner EO, Chew A, Wertheim GB, Levine BL, June CH, Grupp SA, Maude SL. Humanized CD19-Targeted Chimeric Antigen Receptor (CAR) T Cells in CAR-Naive and CAR-Exposed Children and Young Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia. J Clin Oncol. 2021 Sep 20;39(27):3044-3055. doi: 10.1200/JCO.20.03458. Epub 2021 Jun 22.

    PMID: 34156874DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-LymphomaLymphoma, Large B-Cell, Diffuse

Condition Hierarchy (Ancestors)

Leukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLymphoma, B-CellLymphoma, Non-HodgkinLymphoma

Study Officials

  • Carl June, MD

    University of Pennsylvania

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 23, 2015

First Posted

February 27, 2015

Study Start

March 25, 2014

Primary Completion

September 2, 2021

Study Completion

September 2, 2021

Last Updated

September 23, 2021

Record last verified: 2021-09

Locations

US(1)