CD123 Redirected Autologous T Cells for AML

NCT ID: NCT02623582

Last Updated: 2017-10-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2016-11-18

Brief Summary

Pilot open-label study to estimate the feasibility, safety and efficacy of intravenously administered, RNA electroporated autologous T cells expressing anti-CD123 chimeric antigen receptors expressing tandem TCR and 4-1BB (TCR /4-1BB) costimulatory domains (referred to as RNA CART123) in Acute Myeloid Leukemia (AML) subjects.

Conditions

Relapsed or Refractory Acute Myeloid Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

The first 3 subjects to receive RNA CART123 cells will receive up to 3 doses of RNA CART123 cells, with no lymphodepleting chemotherapy prior to infusion.

Group Type: EXPERIMENTAL

Autologous Anti-CD 123 CAR TCR/4-1BB-expressing T-lymphocytes

Intervention Type: BIOLOGICAL

Given IV

Cohort 2

The remaining 12 subjects of the study will receive up to six IV doses of RNA CART123 cells.

Subjects in Cohort 2 may be given lymphodepleting chemotherapy 4 days (+/- 1 day) prior to the first CART123 cell infusion (if ALC> 500/uL).

Lymphodepleting chemotherapy may be repeated before the fourth dose of RNA CART123 cells (if ALC> 500/uL).

Lymphodepleting chemotherapy includes a single dose of cyclophosphamide (1g/m2) Weight used for dosing will be the weight obtained prior to the apheresis procedure Cell numbers are based on CAR+ cells with CAR expression determined by flow cytometry Based on the product release criteria, at least 20% of the total cells will be RNA CART123 cells.

Dosing will not be changed for changes in subject weight The indicated doses are +/- 20% to account for manufacturing variability.

Group Type: EXPERIMENTAL

Autologous Anti-CD 123 CAR TCR/4-1BB-expressing T-lymphocytes

Intervention Type: BIOLOGICAL

Given IV

Cyclophosphamide

Intervention Type: DRUG

Given IV

Interventions

Autologous Anti-CD 123 CAR TCR/4-1BB-expressing T-lymphocytes

Given IV

Intervention Type: BIOLOGICAL

Cyclophosphamide

Given IV

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female subjects 18 years of age or older with AML with no available curative treatment options using currently available therapies
• Subjects must have a suitable stem cell donor available who may donate cells if the subject needs to undergo allogeneic HCT. Donor may be matched or mismatched and must be found to be suitable according to the institution's standard criteria.
• Subjects with second or subsequent relapse, any relapse refractory to salvage, or with persistent disease after at least two lines of therapy.

• Subjects must have evaluable disease defined as >5% blasts on marrow aspirate or biopsy, extramedullary disease (CNS involvement is prohibited), or at least 20% blasts in the peripheral blood within 2 weeks prior to enrollment. Note: subjects with second or subsequent relapse are considered to have evaluable disease even without meeting the above morphologic criteria if they are found to have persistent recurrent disease-associated molecular or cytogenetic abnormalities.
• Creatinine < 1.6 mg/dl
• ALT/AST must be < 5 x upper limit of normal unless related to disease
• Bilirubin < 2.0 mg/dl, unless subject has Gilbert's syndrome (≤3.0 mg/dL);
• ECOG Performance status 0-2.
• Left ventricular ejection fraction > 40% as confirmed by ECHO/MUGA
• Written informed consent is given.
• Subjects of reproductive potential must agree to use acceptable birth control methods.

Exclusion Criteria

• 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 pregnancy test at enrollment. A urine pregnancy test will be performed within 48 hours before infusion.
• HIV infection.
• Active hepatitis B or hepatitis C infection.
• Concurrent use of systemic steroids or immunosuppressant medications. Recent or current use of inhaled steroids or physiologic replacement with hydrocortisone is not exclusionary.
• Absolute lymphocyte count <500/uL
• Any uncontrolled active medical disorder that would preclude participation as outlined.
• Subjects with signs or symptoms indicative of CNS involvement. A CNS evaluation should be performed as clinically appropriate to rule out CNS involvement.
• Known history of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
• Class III/IV cardiovascular disability according to the New York Heart Association Classification.
• Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system
• Subjects with clinically apparent arrhythmia, or arrhythmias that are not stable on medical management, within 2 weeks of the Screening/Enrollment visit.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Saar Gill, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Abramson Cancer Center at Penn Medicine

Locations

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

823175 - UPCC 04415

Identifier Type: -

Identifier Source: org_study_id