NCT04214886

Brief Summary

In this protocol, the investigators hypothesize that modifying the process of producing CAR+ T-cells can help to improve responses and reduce toxicities. Building on previous in vitro studies that have shown successful production of CAR+ T-cells using a new production approach, the investigators are now studying the ability to produce these CAR+ T-cells and determine how well they work in the clinical setting.

Trial Health

75
On Track

Trial Health Score

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

Enrollment
24

participants targeted

Target at P25-P50 for phase_1

Timeline
106mo left

Started Dec 2019

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
active not recruiting

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 Progress42%
Dec 2019Dec 2034

First Submitted

Initial submission to the registry

December 16, 2019

Completed
15 days until next milestone

Study Start

First participant enrolled

December 31, 2019

Completed
2 days until next milestone

First Posted

Study publicly available on registry

January 2, 2020

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 11, 2022

Completed
12.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2034

Expected
Last Updated

August 15, 2022

Status Verified

August 1, 2022

Enrollment Period

2.6 years

First QC Date

December 16, 2019

Last Update Submit

August 11, 2022

Conditions

B-Cell Acute Lymphoblastic Leukemia, AdultB-cell Lymphoma RefractoryB-cell Lymphoma Recurrent

Keywords

LeukemiaLymphomaCAR TChimericCD19

Outcome Measures

Primary Outcomes (2)

  • Successful production of CD19-CD34 CAR product that meet predefined release criteria (cell viability/cell number/transduction efficiency/negative sterility and viral testing) for enrolled patients

    24 participants evaluated for determination of the feasibility of producing CD19-CD34 CAR T cells meeting the established release criteria

    18 months

  • Adverse events

    24 participants evaluated for adverse event and grading by using CTCAE v.5.0 to determine the maximal tolerated dose of CD19-CD34 CAR T cells with chemotherapy conditioning regimen for patients that have recurrent or refractory B cell malignancies

    15 years

Secondary Outcomes (3)

  • Response to treatment

    24 months

  • Progression free survival

    24 months

  • Overall survival

    15 years

Other Outcomes (1)

  • Immune response

    15 years

Study Arms (4)

CAR 5 x 105 transduced T cells/kg (Dose Level -1)

EXPERIMENTAL

Autologous peripheral blood mononuclear cell (PBMC) will be obtained by leukapheresis over one day. Daily intravenous (IV) infusion of fludarabine and cyclophosphamide for total of 3 days (Days -5, -4, -3). The dose of cyclophosphamide will be given at 500mg/m2. The dose of fludarabine will be given at 30mg/m2. CD19-CD34 CAR transduced T cells will be administered IV at a dose level of 5 x 105 transduced T cells/kg.

Drug: FludarabineDrug: CyclophosphamideBiological: CD19-CD34 CAR transduced T cells

CAR 1 x 106 transduced T cells/kg (Dose Level 1)

EXPERIMENTAL

Autologous peripheral blood mononuclear cell (PBMC) will be obtained by leukapheresis over one day. Daily intravenous (IV) infusion of fludarabine and cyclophosphamide for total of 3 days (Days -5, -4, -3). The dose of cyclophosphamide will be given at 500mg/m2. The dose of fludarabine will be given at 30mg/m2. CD19-CD34 CAR transduced T cells will be administered IV at a dose level of 1 x 106 transduced T cells/kg.

Drug: FludarabineDrug: CyclophosphamideBiological: CD19-CD34 CAR transduced T cells

CAR 1.5 x 106 transduced T cells/kg (Dose Level 2)

EXPERIMENTAL

Autologous peripheral blood mononuclear cell (PBMC) will be obtained by leukapheresis over one day. Daily intravenous (IV) infusion of fludarabine and cyclophosphamide for total of 3 days (Days -5, -4, -3). The dose of cyclophosphamide will be given at 500mg/m2. The dose of fludarabine will be given at 30mg/m2. CD19-CD34 CAR transduced T cells will be administered IV at a dose level of 1.5 x 106 transduced T cells/kg.

Drug: FludarabineDrug: CyclophosphamideBiological: CD19-CD34 CAR transduced T cells

CAR 2 x 106 transduced T cells/kg (Dose Level 3)

EXPERIMENTAL

Autologous peripheral blood mononuclear cell (PBMC) will be obtained by leukapheresis over one day. Daily intravenous (IV) infusion of fludarabine and cyclophosphamide for total of 3 days (Days -5, -4, -3). The dose of cyclophosphamide will be given at 500mg/m2. The dose of fludarabine will be given at 30mg/m2. CD19-CD34 CAR transduced T cells will be administered IV at a dose level of 2 x 106 transduced T cells/kg.

Drug: FludarabineDrug: CyclophosphamideBiological: CD19-CD34 CAR transduced T cells

Interventions

FludarabineDRUG

Fludarabine is an anti-cancer drug acting as an antimetabolite that is used to treat leukemia and lymphoma cancers.

CAR 1 x 106 transduced T cells/kg (Dose Level 1)CAR 1.5 x 106 transduced T cells/kg (Dose Level 2)CAR 2 x 106 transduced T cells/kg (Dose Level 3)CAR 5 x 105 transduced T cells/kg (Dose Level -1)
CyclophosphamideDRUG

Cyclophosphamide is is an anti-cancer drug acting as an alkylating agent that is used to treat leukemia and lymphoma cancers.

CAR 1 x 106 transduced T cells/kg (Dose Level 1)CAR 1.5 x 106 transduced T cells/kg (Dose Level 2)CAR 2 x 106 transduced T cells/kg (Dose Level 3)CAR 5 x 105 transduced T cells/kg (Dose Level -1)
CD19-CD34 CAR transduced T cellsBIOLOGICAL

CD19-CD34 CAR transduced T cells are the subject's own immune cells that target B cell markers on cancer cells.

CAR 1 x 106 transduced T cells/kg (Dose Level 1)CAR 1.5 x 106 transduced T cells/kg (Dose Level 2)CAR 2 x 106 transduced T cells/kg (Dose Level 3)CAR 5 x 105 transduced T cells/kg (Dose Level -1)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Participants must be greater than or equal to 18 years of age.
  • Participants must have Eastern cooperative oncology group (ECOG) performance status of 0 or 1, or Karnofsky greater than or equal to 80%
  • Participants must have been diagnosed with histologically confirmed aggressive B cell NHL that is refractory / recurrent.
  • Participants must have been diagnosed with histologically confirmed B-ALL that is refractory / recurrent.
  • All subjects must have evaluable or measurable disease; subjects with lymphoma must have evaluable or measurable disease according to the revised IWG Response Criteria for Malignant Lymphoma. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy. ALL patients must have at least 5% blasts in the bone marrow
  • Adequate performance status; adequate organ and marrow function as defined by (supportive care is allowed per institutional standards, i.e. filgrastim, transfusion):
  • ANC ≥ 750/uL\*
  • Platelet count ≥ 50,000/uL\*
  • Absolute lymphocyte count ≥ 150/uL\*
  • Adequate renal, hepatic, pulmonary and cardiac function defined as:
  • SaO2 ≥ 92% on room air
  • Creatinine ≤ 2 mg/dL or Creatinine Clearance ≥ 60 mL/min (as estimated by Cockcroft Gault)
  • Total bilirubin ≤ 1.5 mg/dL (except in subjects with Gilbert's disease) (Elevations related to leukemia or lymphoma involvement of the liver will not disqualify a subject)
  • Serum ALT/AST ≤3x ULN or ≤5X if there is hepatic involvement due to malignancy
  • Cardiac ejection fraction (LVEF) ≥ 45%)
  • +14 more criteria

You may not qualify if:

  • Participants must not have an active bacterial, viral, fungal or other infection.
  • Participants must not have a history of HIV or current hepatitis B or hepatitis C virus
  • Participants must not have a history of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment, or have cardiac atrial or cardiac ventricular lymphoma involvement.
  • No history of severe, immediate hypersensitivity reaction attributed to compounds of similar chemical or biologic composition to any agents used in study.
  • No active CNS disorder, or history of MI, cardiac angioplasty or stenting, unstable angina or other clinically significant cardiac disease with 12 months of enrollment, or have cardiac atrial or ventricular lymphoma involvement.
  • Not receiving anticoagulation therapy
  • Not have primary immunodeficiency or history of autoimmune disease (e.g. Crohns, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
  • History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, and breast) unless disease free for at least 1 year. Patients who are on adjuvant therapy with no evidence of active disease are deemed eligible for the trial

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Loyola University

Maywood, Illinois, 60153, United States

Location

MeSH Terms

Conditions

Burkitt LymphomaLeukemiaLymphoma

Interventions

fludarabineCyclophosphamide

Condition Hierarchy (Ancestors)

Epstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLymphoma, B-CellLymphoma, Non-HodgkinNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesHematologic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Study Officials

  • Nasheed Hossain, MD

    Loyola University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: Autologous peripheral blood mononuclear cell (PBMC) will be obtained by leukapheresis over one day. Daily intravenous (IV) infusion of fludarabine and cyclophosphamide for total of 3 days (Days -5, -4, -3). The dose of cyclophosphamide will be given at 500mg/m2. The dose of fludarabine will be given at 30mg/m2. CD19-CD34 CAR transduced T cells administration will follow a Phase I dose escalation design. Each Cohort will start will with the goal of accruing three participants to determine the dose limiting toxicities. Once the maximum tolerated dose is established, an expansion cohort will be treated to include a total of 6 participants.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, Assistant Professor

Study Record Dates

First Submitted

December 16, 2019

First Posted

January 2, 2020

Study Start

December 31, 2019

Primary Completion

August 11, 2022

Study Completion (Estimated)

December 31, 2034

Last Updated

August 15, 2022

Record last verified: 2022-08

Data Sharing

IPD Sharing
Will not share

Locations

US(1)