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Leukapheresis for CAR-Therapy Manufacturing

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ClinicalTrials.gov Identifier: NCT03226704
Recruitment Status : Recruiting
First Posted : July 24, 2017
Last Update Posted : January 15, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief 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 4-30 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. Some will also be screened with:

X-rays

Scans

Spinal fluid samples

Bone marrow aspiration and biopsy

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.


Condition or disease
Leukemia Lymphoma Acute Lymphoblastic Leukemia Diffuse Large B-Cell Lymphoma Non-Hodgkin's Lymphoma

Detailed Description:

Background:

  • Leukapheresis is a necessary step to developing a CAR therapy cellular product. 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 product on a subsequent therapeutic clinical trial, which can be administered when the patient needs investigational therapies.
  • 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.

Objective:

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

Eligibility:

-Patients 3-30 years of age, at least 15 kg, with relapsed/refractory leukemia or lymphoma 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 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 therapy trials, we expect this study to remain open for up to 5 years for a total of 120 patients to be enrolled.

Study Type : Observational
Estimated Enrollment : 120 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Leukapheresis for CAR-Therapy Manufacturing
Actual Study Start Date : August 14, 2017
Estimated Primary Completion Date : July 31, 2022
Estimated Study Completion Date : July 31, 2022


Group/Cohort
1
Patients 3-30 years of age, at least 15 kg, with relapsed/refractory leukemia or lymphoma; ORpreviously treated patients without detectable disease at the time of leukapheresis but at high-relapse risk.



Primary Outcome Measures :
  1. Fraction of subjects who can enroll on a CAR-T study within approximately 6 months of undergoing apheresis [ Time Frame: 6 months after collection of apheresis product ]
    number of subjects who enroll on a CAR-T study within approximately 6 months of undergoing apheresis


Secondary Outcome Measures :
  1. Fraction of patients who experience a grade 4 toxicity associated with apheresis [ Time Frame: completion of apheresis procedure ]
    number of patients who experience a grade 4 toxicity associated with apheresis



Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients 3-30 years of age, at least 15 kg, with relapsed/refractory leukemia or lymphoma; OR previously treated patients without detectable disease at the time of leukapheresis but at high-relapse risk.@@@
Criteria
  • INCLUSION CRITERIA:
  • Age: greater than or equal to 4 and greater than or equal to 30 years
  • Weight greater than or equal to 15 kg
  • Confirmation of leukemia or lymphoma diagnosis provided by prior flow cytometry, PCR or H&E verification.
  • Disease Status:

    • Relapsed/refractory leukemia or lymphoma 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 therapy based on the following:

    • Adequate performance status: Patients > 10 years of age: Karnofsky greater than or equal to 50%; Patients less than or equal to 10 years of age: Lansky scale greater than or equal to 50%
    • Adequate organ function:
    • absolute neutrophil count >750/mcL*
    • platelets greater than or equal to 50,000/mcL*
    • total bilirubin less than or equal to 2 X ULN (except in the case of subjects with documented Gilbert s disease > 3x ULN)

AST(SGOT)/ALT(SGPT) less than or equal to 20 X institutional upper limit of normal for age and laboratory normal ranges

creatinine within age adjusted normal institutional limits (see table below)

OR

creatinine clearance greater than or equal to 60 mL/min/1.73 m2 for patients with

creatinine levels above institutional normal.

Age

(Years)

Maximum Serum

Creatinine (mg/dL)

Less than or equal to 5 0.8

5 < age less than or equal to 10 1.0

>10 1.2

* These cytopenias deemed to be disease-related and not therapy-related are exempt from this exclusion.

-Patients, parents/guardian(s), 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 maintained greater than or equal to 50,000/mcL
  • Active DIC, bleeding or coagulopathy which cannot be corrected with minimal intervention
  • Rapidly progressive disease or hyperleukocytosis greater than or equal to 50,000 blasts/mcL
  • Symptomatic, uncontrolled or severe intercurrent illness that would compromise the ability to tolerate CAR therapy based toxicity
  • Systemic chemotherapy less than or equal to 2 weeks (6 weeks for clofarabine or nitrosoureas) or radiation therapy less than or equal to 3 weeks prior to leukapheresis; with the following exception
  • Maintenance chemotherapy will be allowed up to one week prior to apheresis (there will be no wash-out required for steroids).
  • Other anti-neoplastic investigational agents currently or within 30 days prior to leukapheresis (i.e. start of protocol therapy);
  • 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.
  • Prior monoclonal antibody therapy within 5 half-lives or 7 days prior to leukapheresis, whichever is greater.
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03226704


Contacts
Contact: Leah E Hoffman, R.N. (240) 858-3828 ncipbllbmt@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Nirali N Shah, M.D. National Cancer Institute (NCI)

Additional Information:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03226704     History of Changes
Other Study ID Numbers: 170137
17-C-0137
First Posted: July 24, 2017    Key Record Dates
Last Update Posted: January 15, 2019
Last Verified: December 6, 2018

Studies a U.S. FDA-regulated Drug Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
CD19
CD22
CD19/22
Immunotherapy
Apheresis

Additional relevant MeSH terms:
Lymphoma
Leukemia
Lymphoma, Non-Hodgkin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases