Leukapheresis for CAR or Adoptive Cell Therapy Manufacturing

  • STATUS
    Recruiting
  • End date
    Jul 31, 2023
  • participants needed
    120
  • sponsor
    National Cancer Institute (NCI)
Updated on 22 May 2021
cancer
remission
lymphoma
white blood cell count
flow cytometry
leukemia
cytopenia
white blood cells
PCR test
neutrophil count
blood cell count

Summary

Background

Leukapheresis is a procedure to separate and collect white blood cells. It is the first step in a treatment called CAR (chimeric antigen receptor) T-cell therapy. CAR-T therapy may be offered to people when their cancer comes back. The collected T-cells are used to make a special version of T-cells called CARs. Researchers want to collect these cells from people who may become eligible for a CAR T-cell study in the future.

Objective

To identify people who have a high likelihood to benefit from CAR T-cell therapy early in their disease course and collect and store a T-cell product.

Eligibility

People ages 4-39 with a form of leukemia or lymphoma that has not been cured by standard therapy

Design

Participants will be screened with medical history, physical exam, and blood and urine tests. Review of existing MRI, x-ray, pathology specimens/reports or CT images may be done.

On this study, participants will have leukapheresis. A needle will be placed into the arm. Blood will be collected and go through a machine. White blood cells will be taken out by the machine. The plasma and red cells will be returned to the participant through a second needle in the other arm. The procedure will take 4-6 hours. Some participants may have a central line (catheter) inserted which is needed to do the leukapheresis procedure, instead of the needles in the arms-especially if they are smaller. For a central line placement, a long thin tube is inserted through a small incision into the main blood vessel leading into the heart that would allow access to the blood to do the leukapheresis procedure.

Participants cells will be processed and frozen for future use in a CAR T-cell therapy study.

Description

Background
  • Leukapheresis is a necessary step to developing a "CAR therapy" or other adoptive cellular therapy products. There are numerous clinical trials underway in the NCI utilizing CAR therapy.
  • The purpose of this protocol is to develop a streamlined process whereby patients undergo apheresis for development of a CAR cell or other adoptive cell therapy product on a subsequent therapeutic clinical trial, which can be administered when the patient needs investigational therapies.
  • Emerging data suggests the critical importance of elements of the apheresis product in outcomes following adoptive cell therapy. Evaluation of methodologies to optimize timing and composition of the apheresis collection are imperative to the feasibility of manufacturing and remains an active area of investigations. Patient specific elements (e.g., presence of NK-cells/circulating leukemic blasts and/or inhibitory myeloid derived suppressor cells) along with other parameters of the apheresis product itself appear to influence efficacy and toxicity profiles of adoptive cell therapy.
  • Allowing for collection of the leukapheresis product in a protocol separate from the therapeutic protocol would allow for the best optimization of:
  • Patient care and disease burden
  • Timing and coordination of cell infusion
  • Collection in patients with high-risk disease who have no current detectable disease but have a very high likelihood of relapse.
  • Comprehensive evaluation of apheresis products will facilitate enhanced understanding of critical elements of the apheresis product in patients with cancer and how this may impact outcomes of adoptive cell therapy.
    Objective

To obtain via the leukapheresis process by which cells will be collected and stored for use in CCR CAR or other adoptive cell therapy clinical trials.

Eligibility

Patients 3-39 years of age, at least 15 kg, with relapsed/refractory cancer that has recurred after or not responded to one or more standard regimens and/or deemed incurable by standard therapy and who meet all eligibility criteria are eligible to participate.

Design
  • Once a patient is determined to be a potential candidate for one of the NCI CAR or other adoptive cell therapy clinical trials, they will undergo leukapheresis, as estimated by recipient weight and target cell harvest dose in the Department of Transfusion Medicine (DTM).
  • No treatments, investigational or standard therapy will be administered on this protocol.
  • Up to 24 patients per year may be enrolled on this study. In planning for future CAR and adoptive cell therapy trials, we expect this study to remain open for up to 5 years for a total of 120 patients to be enrolled.

Details
Condition childhood ALL, Diffuse Large B-Cell Lymphoma, Lymphoma, leukemia, Lymphoproliferative Disorder, Lymphoma, Non-Hodgkin's Lymphoma, Leukemia (Pediatric), Lymphocytic Leukemia, Acute, Lymphoproliferative disorders, acute lymphoblastic leukemia, leukemia, acute lymphoblastic, non-hodgkin's lymphoma (nhl), leukemias, lymphomas, diffuse large cell lymphoma, diffuse large b cell lymphoma, acute lymphoid leukaemia, acute lymphocytic leukemia, acute lymphoblastic leukemia (all)
Clinical Study IdentifierNCT03226704
SponsorNational Cancer Institute (NCI)
Last Modified on22 May 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Age: >= 3 and <= 39 years
Weight >= 15 kg
Confirmation of cancer diagnosis provided by disease-specific assessment (e.g., flow cytometry, PCR) or H&E verification
Disease Status
Relapsed/refractory cancer that has failed one standard and one salvage therapy and are not in remission at the time of leukapheresis, OR
Previously treated patients without detectable disease at the time of leukapheresis but at high-relapse risk
Potentially eligible for future NIH-CAR or other adoptive cell therapy based on the
following
Adequate performance status: Patients > 10 years of age: Karnofsky >= 50%; Patients <= 10 years of age: Lansky scale >= 50%
Adequate organ function
absolute neutrophil count >750/mcL
platelets >=30,000/mcL
total bilirubin <=2 X ULN (except in the case of subjects with documented Gilbert s disease > 3x ULN)
AST(SGOT)/ALT(SGPT)<=20 X institutional upper limit of normal for age and
laboratory normal ranges
creatinine within age adjusted normal institutional limits (see below) OR
creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels
above institutional normal
Age (Years): <=5; Maximum Serum Creatine (mg/dL): 0.8
Age (Years): 5 < age <= 10; Maximum Serum Creatine (mg/dL): 1.0
Age (Years): >10; Maximum Serum Creatine (mg/dL): 1.2
Cytopenias deemed to be disease-related and not therapy-related are exempt from this exclusion
Patients, parents/guardians, legally authorized representative (LAR), or durable power of attorney must be able to give consent and sign the Informed Consent Document

Exclusion Criteria

Transfusion refractory thrombocytopenia such that platelet count cannot be adequately supported with transfusions to be at >=30,000/mcL
Active DIC, bleeding or coagulopathy which cannot be corrected with minimal intervention
Rapidly progressive disease or hyperleukocytosis >= 50,000 blasts/mcL
Symptomatic, uncontrolled or severe intercurrent illness that would compromise the ability to tolerate CAR or adoptive cell therapy-based toxicity
Subjects must have recovered from the acute side effects of their prior therapy, such that eligibility criteria are met. Cytopenias deemed to be disease-related and not therapyrelated are exempt from this exclusion
Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test at screening
Active or latent hepatitis B or active hepatitis C, or any uncontrolled infection at screening
Human Immunodeficiency Virus (HIV) infection at screening (The experimental treatments being evaluated depend upon an intact immune system. Patients who are HIV seropositive can have decreased immune competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities)
Any patient that in the opinion of the investigator is not medically stable to undergo the leukapheresis procedure or will not comply with the visit schedules or procedures
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