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CAR T-cell Therapy

CAR-T Cell Therapy for B-Cell Lymphoma

Phase 1

Recruiting

Led By Natalie Grover, MD

Research Sponsored by UNC Lineberger Comprehensive Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subjects must have received specific prior lines of therapy based on lymphoma subtype

Karnofsky score of > 60%

Must not have

Tumor in a location causing airway obstruction

Current use of systemic corticosteroids at high doses

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 15 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new cancer treatment that combines T cells and antibodies to create a more effective treatment than either alone. So far it has caused side effects including cytokine release syndrome and neurotoxicity, but the goal is to find a dose of the second study drug, AP1903, that reduces the severity of the cytokine release syndrome and/or neurotoxicity, but still allows the remaining iC9-CAR19 cells to effectively fight the lymphoma.

Who is the study for?

This trial is for adults over 18 with certain types of B-cell lymphoma or leukemia who have tried at least two other treatments without success. It's not for pregnant women, those with severe hepatitis B, or HIV/HTLV/HCV infections. Participants must be willing to use birth control and have a Karnofsky score above 60%, indicating they can care for themselves.

What is being tested?

The study tests iC9-CAR19 T cells designed to target CD19 on cancer cells, combined with chemotherapy drugs like Bendamustine and Fludarabine. If severe side effects occur, AP1903 is used to activate a 'safety switch' in the T cells to reduce their activity.

What are the potential side effects?

Potential side effects include cytokine release syndrome (a rapid release of cytokines into the blood) and neurotoxicity (damage to nerve tissue). The safety switch aims to mitigate these by deactivating some T cells if necessary.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have received treatments specific to my type of lymphoma.

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I am able to care for myself but may not be able to do active work.

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My diagnosis is B-cell Non-Hodgkin Lymphoma.

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My lymphoma has spread to my brain or spinal cord.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My tumor is blocking my airways.

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I am currently taking high doses of corticosteroids.

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I do not have an active infection with any major viruses.

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My organs are functioning well enough for treatment.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 15 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~15 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 15 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of participants with adverse events as a measure of safety and tolerability of iC9-CAR19 T cells

Secondary study objectives

Change in health related quality of life

Change in patient-reported symptoms

Change in physical function

+6 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Single Arm iC9.CAR19 T cellsExperimental Treatment5 Interventions

The safety of iC9-CAR19 cells will be investigated using the 3+3 design. Dose level (DL) Dose (#transduced cells/kg) -1 1 x 10\^5 1. 1 x 10\^6 2. 2 x 10\^6 DL1 will enroll 3 subjects. If no toxicity within 4 weeks, then DL 2 will enroll 3 subjects. If toxicity in 1/3 subjects in DL 1, 3 more subjects will be enrolled. If DL 1 is not tolerable, a de-escalation to DL -1 will enroll 3 subjects. If 3 subjects at the higher dose do not have DLTs more will be enrolled at that dose to get more information about toxicity. Lymphodepleting chemotherapy of IV bendamustine 70 mg/m2 and IV fludarabine 30 mg/m2/day for 3 consecutive days will be given within 2-14 days prior to cell infusion. AP1903 (0.4 mg/kg), a dimerizing agent to engage and activate the caspase 9 safety switch to trigger iC9-CAR19 T cell death by apoptosis will be given to subjects who develop severe cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS).

Group II: Expansion Cohort iC9-CAR19 cellsExperimental Treatment5 Interventions

After the tolerable cell dose (TCD) has been determined in adults, up to 18 additional subjects may be enrolled in an expansion cohort at the TCD. A TCD is defined as the dose at which approximately 0.20 of subjects experience dose limiting toxicity (0 - 1 out of 6 subjects).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

AP1903

2014

Completed Phase 2

~90

Fludarabine

2012

Completed Phase 4

~1860