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B-Cell Acute Lymphoblastic Leukemia, AdultPhase 1NCT04214886

CD19 Chimeric Antigen Receptor (CAR) T Cells for Adults With Recurrent or Refractory B Cell Malignancies

A Phase 1 study testing Fludarabine, Cyclophosphamide and CD19-CD34 CAR transduced T cells in people with B-Cell Acute Lymphoblastic Leukemia, Adult and B-cell Lymphoma Refractory, run by Loyola University at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Fludarabine, Cyclophosphamide and CD19-CD34 CAR transduced T cells
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteUnited States
Study dates
31 Dec 2019to 31 Dec 2034
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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):
Show all 29Show fewer
  • 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%)
  • Subjects with ALL or B-NHL with CNS1, or CNS1a, 2b, 2c are eligible only in the absence of neurologic symptoms suggestive of CNS disease involvement such as cranial nerve palsy.
  • If patients previously had CNS disease and are disease free after treatment with no clinical concerns for recurrent disease they are eligible for enrollment.
  • Subjects with history of allogeneic SCT must be at least 100 days from SCT, have no evidence of Graft versus Host Disease (GvHD), and no longer taking immunosuppressive agents for at least 30 days prior to enrollment. However, patients with grade 1 skin GVHD or low grade cGHVD <3 who are not requiring systemic therapy are eligible.
  • Females of child bearing potential and males of child fathering potential must be willing to practice birth control during and for 4 months post therapy.
  • Females of child bearing potential must have negative pregnancy test.
  • Must meet wash out period since prior therapies.
  • At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy, which requires 5 half-lives
  • Must have recovered from acute side effects from prior therapy to meet eligibility.
  • If had prior CAR therapy, 30 days must have elapsed prior to apheresis; may not have evidence of persistence of CAR T cells in blood samples (circulating levels of genetically modified cells of ≥ 5% by flow cytometry)
  • No active HIV or active HBV/HCV infection. Patients with history of HBV or HCV who are PCR negative after appropriate therapy are eligible. Patients may not have any other uncontrolled, symptomatic, intercurrent illness.
  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Loyola University

    Maywood, Illinois, 60153

Other trials in United States

About this study

Official title: Dose Escalation Study of CD19 Chimeric Antigen Receptor (CAR) T Cells With a CD34 Selection Marker in Adults With Recurrent or Refractory B Cell Malignancies

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.

Read the detailed description

Autologous peripheral blood mononuclear cell (PBMC) will be obtained by leukapheresis over one day and the cells will be transduced with an in house designed CAR retroviral vector. Participants will receive daily intravenous (IV) infusion of lymphodepleting regimen 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. Participants will receive the CAR transduced T cells IV infusion in the BMT Inpatient Unit and remain admitted for close monitoring for at least the first 7 days following the cell infusion (D0 to Day +7), possibly longer if any side effects are encountered. The CAR transduced T cells will be escalated from 1 x 106 transduced T cells/kg (± 20%) to 2 x 106 transduced T cells/kg (± 20%) in a Phase I design, based on toxicity. Once discharged from the inpatient unit, for the next 7 days (Day +8 to Day +14) the patients will be evaluated in the High Dose Unit (labs and physical exam) to screen for toxicities.

Being tested
Fludarabine, Cyclophosphamide, CD19-CD34 CAR transduced T cells
Keywords
Leukemia, Lymphoma, CAR T, Chimeric, CD19
Medical subject headings
Burkitt Lymphoma, Leukemia, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FludarabineDrug

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

  • CyclophosphamideDrug

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

  • 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.

Study groups in NCT04214886
Study groupRoleWhat they receive
CAR 5 x 105 transduced T cells/kg (Dose Level -1)ExperimentalAutologous 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.
Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Biological: CD19-CD34 CAR transduced T cells
CAR 1 x 106 transduced T cells/kg (Dose Level 1)ExperimentalAutologous 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.
Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Biological: CD19-CD34 CAR transduced T cells
CAR 1.5 x 106 transduced T cells/kg (Dose Level 2)ExperimentalAutologous 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.
Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Biological: CD19-CD34 CAR transduced T cells
CAR 2 x 106 transduced T cells/kg (Dose Level 3)ExperimentalAutologous 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.
Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Biological: CD19-CD34 CAR transduced T cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 18 months

  2. 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

    Measured: 15 years

Secondary outcomes (3)

  1. Response to treatment

    24 participants evaluated for response to treatment by testing using PET/CT for lymphoma and using bone marrow aspirate for leukemia.

    Measured: 24 months

  2. Progression free survival

    24 participants evaluated for progression by testing using PET/CT for lymphoma and using bone marrow aspirate for leukemia.

    Measured: 24 months

  3. Overall survival

    24 participants evaluated for overall survival by clinical visit

    Measured: 15 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jan 2020
  2. Study start31 Dec 2019
  3. Primary completion11 Aug 2022
  4. Study completion31 Dec 2034 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
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.
Masking
None (open label)
Enrolment
24 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04214886
Sponsor's protocol ID
212594
Status last verified
Aug 2022
First submitted
16 Dec 2019
Last updated
15 Aug 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Fludarabine, Cyclophosphamide and CD19-CD34 CAR transduced T cells in people with B-Cell Acute Lymphoblastic Leukemia, Adult and B-cell Lymphoma Refractory, run by Loyola University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 15 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04214886.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2022.

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