Pilot Trial Of Autologous T Cells Engineered To Express Anti-CD19 Chimeric Antigen Receptor (CART19)In Combination With Ibrutinib In Patients With Relapsed Or Refractory CD19+ Chronic Lymphocytic Leukemia (CLL)Or Small Lymphocytic Lymphoma (SLL)

NCT02640209 | Terminated Early Phase 1 DMC FDA Drug

• 1 other identifier: UPCC 18415, 823584
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Open-label pilot study to determine safety and efficacy of CART-19 cells in combination with ibrutinib. The target dose will be 1-5x10xE8 CART-19 transduced cells administered via split dosing: 10% on Day 1, 30% on Day 2, 60% on Day 3. 15 evaluable subjects (adults) with relapsed or refractory CLL/SLL who have achieved partial response or stable disease on ibrutinib therapy will be eligible to receive CART-19 therapy.

Conditions

LYMPHOCYTIC LEUKEMIA (CLL) OR SMALL LYMPHOCYTIC LYMPHOMA (SLL)

Outcome Measures

Primary Outcomes (1)

• Number of Adverse Events

  26 months

Study Arms (1)

Arm 1

EXPERIMENTAL

Biological: CART 19

Interventions

CART 19 BIOLOGICAL

The target dose range administered in this study is 1-5x108 CART-19 cells administered via split dosing: 10% on Day 1 (1-5x107 CART19), 30% on Day 1 (3x107-1.5x108 CART19), 60% on Day 2 (6x107-3x108 CART19).

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented CD19+ CLL or SLL
• Successful test expansion -cells (as described in Section 6.1)
• Patients must have failed at least 1 prior regimen before Ibrutinib (not including single agent rituximab or single agent corticosteroids)
• a. Note: Any relapse after prior autologous SCT will make the patient eligible regardless of other prior therapy.
• Patients must be currently receiving ibrutinib for at least 6 months prior to enrollment in the study and:
• Not experiencing any ≥ grade 2 non-hematologic ibrutinib-related toxicity
• The best response to ibrutinib therapy must not have exceeded partial response or stable disease (i.e. no CR or CRi)
• Note: Patients carrying a deletion at chromosome 17p (i.e. del\[17p\]), and/or TP53, BTK, and at the PLCγ2 loci mutations, will be eligible if they are receiving frontline therapy with ibrutinib.
• ECOG Performance status 0 or 1
• years of age and older
• Adequate organ system function including:
• Creatinine \< 1.6 mg/dl
• ALT/AST \< 3x upper limit of normal
• Total Bilirubin \<2.0 mg/dl with the exception of patients with Gilbert syndrome; patients with Gilbert syndrome may be included if their total bilirubin is ≥ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN.
• Have no active GVHD and require no immunosuppression

You may not qualify if:

• CLL patients with known or suspected transformed disease (i.e. Richter's transformation). Note: biopsy proven absence of transformation is not required.
• 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.
• Any uncontrolled active medical disorder that would preclude participation as outlined.
• HIV infection.
• Patients with active CNS involvement with malignancy. Patients with prior CNS disease that has been effectively treated will be eligible providing treatment was \>4 weeks before enrollment.
• Class III/IV cardiovascular disability according to the New York Heart Association Classification.
• Subjects with clinically apparent arrhythmia or arrhythmias who are not stable on medical management within two weeks of enrollment.
• Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system.

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (2)

• Gill S, Vides V, Frey NV, Hexner EO, Metzger S, O'Brien M, Hwang WT, Brogdon JL, Davis MM, Fraietta JA, Gaymon AL, Gladney WL, Lacey SF, Lamontagne A, Mato AR, Maus MV, Melenhorst JJ, Pequignot E, Ruella M, Shestov M, Byrd JC, Schuster SJ, Siegel DL, Levine BL, June CH, Porter DL. Anti-CD19 CAR T cells in combination with ibrutinib for the treatment of chronic lymphocytic leukemia. Blood Adv. 2022 Nov 8;6(21):5774-5785. doi: 10.1182/bloodadvances.2022007317.

  PMID: 35349631 DERIVED

• Frey NV, Gill S, Hexner EO, Schuster S, Nasta S, Loren A, Svoboda J, Stadtmauer E, Landsburg DJ, Mato A, Levine BL, Lacey SF, Melenhorst JJ, Veloso E, Gaymon A, Pequignot E, Shan X, Hwang WT, June CH, Porter DL. Long-Term Outcomes From a Randomized Dose Optimization Study of Chimeric Antigen Receptor Modified T Cells in Relapsed Chronic Lymphocytic Leukemia. J Clin Oncol. 2020 Sep 1;38(25):2862-2871. doi: 10.1200/JCO.19.03237. Epub 2020 Apr 16.

  PMID: 32298202 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Saar Gill, MD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 22, 2015
• First Posted: December 28, 2015
• Study Start: January 29, 2016
• Primary Completion: October 15, 2018
• Study Completion: July 16, 2019
• Last Updated: June 22, 2023

Record last verified: 2020-05

Locations

US (1)