Phase I/IIA Study of CART19 Cells for Patients With Chemotherapy Resistant or Refractory CD19+ Leukemia and Lymphoma

NCT01626495 | Completed Phase 1 Results DMC

• 2 other identifiers: 10-007706, 815870CHP959
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

Brief Summary

This is a study for children who have been previously treated for Leukemia/Lymphoma. In particular, it is a study for people who have a type of Leukemia/Lymphoma that involves B cells (a type of white cell), which contain the cancer. This is a new approach for treatment of Leukemia/Lymphoma that involves B cells (tumor cells). This study will take the subject's white blood cells (T cells) and modify them in order to target the cancer. The subject's T cells will be modified in one or two different ways that will allow the cells to identify and kill the tumor cells (B cells). Both ways of modifying the cells tells the T cells to go to the B cells (tumor cells) and turn "on" and potentially kill the B cells (tumor cells). The modification is a genetic change to the T cells, or gene transfer, in order to allow the modified T cells to recognize your tumor cells but not other normal cells in the subject's body. These modified cells are called chimeric antigen receptor 19 (CART19) T-cells.

Conditions

B Cell Leukemia; B Cell Lymphoma

Keywords

Biological: CART19

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With Study Related Adverse Events.

  Inclusive of any events that are "possibly", "likely", or "definitely" related to study treatment any time from the first day of study treatment until week 24.

  24 weeks

Secondary Outcomes (3)

• The Number of Subjects With a Successful Product Manufactured

  24 weeks

• Number of Subjects With Complete Remission (CR).

  4 Weeks

• Number of Subjects With Complete Remission With Incomplete Blood Count Recovery (CRi).

  4 Weeks

Study Arms (1)

CART-19 T Cells

EXPERIMENTAL

The subject's thawed T cells will be modified in one or two different ways that will allow the cells to identify and kill the tumor cells (B cells). The T cells will be infused over 10-15 minutes on days Days 0, and 1. Day 14 is tentative based on response.

Biological: CART-19

Interventions

CART-19 BIOLOGICAL

Day 0: 10% of total dose Day 1: 30% of total dose if patient is stable (no significant toxicity) from prior dose.

CART-19 T Cells

Eligibility Criteria

• Age: 1 Year - 24 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male and female subjects with CD 19+ B cell malignancies in patients with 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: CD 19+ leukemia or lymphoma
• ALL without curative options for therapy, including those not eligible for allogeneic
• SCT because of:
• age
• co-morbid disease
• other contraindications to TBI-based conditioning (required for ALL SCT)
• lack of suitable donor
• prior SCT
• Declines allo SCT (in CR3) as a therapeutic option after documented discussion about the role of SCT with a BMT physician not part of the study team. Note: 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.
• Follicular lymphoma, previously identified as CD19+
• At least 2 prior combination chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy.
• Stage III-IV disease.
• Less than 1 year between last chemotherapy and progression (i.e. most recent progression free interval \<1 year).
• Disease responding or stable after most recent therapy (chemotherapy, MoAb).

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 inhaled steroids, or hydrocortisone for physiological replacement in patients with adrenal insufficiency are permitted as well
• Presence of grade 2-4 acute or extensive chronic GVHD
• Under treatment for GVHD
• Previous treatment with any gene therapy products
• Any uncontrolled active medical disorder that would preclude participation as outlined.
• HIV infection.
• CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

CHOP - http://www.chop.edu/service/oncology/pediatric-cancer-research/cart-19-trial.html

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (3)

• Gofshteyn JS, Shaw PA, Teachey DT, Grupp SA, Maude S, Banwell B, Chen F, Lacey SF, Melenhorst JJ, Edmonson MJ, Panzer J, Barrett DM, McGuire JL. Neurotoxicity after CTL019 in a pediatric and young adult cohort. Ann Neurol. 2018 Oct;84(4):537-546. doi: 10.1002/ana.25315. Epub 2018 Sep 26.

  PMID: 30178481 DERIVED

• Fitzgerald JC, Weiss SL, Maude SL, Barrett DM, Lacey SF, Melenhorst JJ, Shaw P, Berg RA, June CH, Porter DL, Frey NV, Grupp SA, Teachey DT. Cytokine Release Syndrome After Chimeric Antigen Receptor T Cell Therapy for Acute Lymphoblastic Leukemia. Crit Care Med. 2017 Feb;45(2):e124-e131. doi: 10.1097/CCM.0000000000002053.

  PMID: 27632680 DERIVED

• Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF, Mahnke YD, Melenhorst JJ, Rheingold SR, Shen A, Teachey DT, Levine BL, June CH, Porter DL, Grupp SA. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014 Oct 16;371(16):1507-17. doi: 10.1056/NEJMoa1407222.

  PMID: 25317870 DERIVED

MeSH Terms

Conditions

Leukemia, B-Cell; Lymphoma, B-Cell

Interventions

CTL019 chimeric antigen receptor

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma

Results Point of Contact

• Title: Regulatory Lead
• Organization: University of Pennsylvania

psom-ind-ide@pobox.upenn.edu

215-662-4484

Study Officials

• Stephan A Grupp, MD,PhD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

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: June 18, 2012
• First Posted: June 22, 2012
• Study Start: August 17, 2011
• Primary Completion: May 7, 2018
• Study Completion: July 11, 2019
• Last Updated: March 23, 2020
• Results First Posted: March 23, 2020

Record last verified: 2020-03

Locations

US (1)