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Administration of T Lymphocytes for Prevention of Relapse of Lymphomas

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ClinicalTrials.gov Identifier: NCT02663297
Recruitment Status : Recruiting
First Posted : January 26, 2016
Last Update Posted : January 29, 2019
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center

Brief Summary:

The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancer. This research study combines two different ways of fighting disease: antibodies and T cells. Antibodies are proteins that protect the body from disease caused by bacteria or toxic substances. Antibodies work by binding those bacteria or substances, which stops them from growing and causing bad effects. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected. Both antibodies and T cells have been used to treat patients with cancers. They both have shown promise, but neither alone has been sufficient to cure most patients. This study is designed to combine both T cells and antibodies to create a more effective treatment. The treatment that is being researched is called autologous T lymphocyte chimeric antigen receptor cells targeted against the CD30 antigen (ATLCAR.CD30) administration.

In previous studies, it has been shown that a new gene can be put into T cells that will increase their ability to recognize and kill cancer cells. A gene is a unit of DNA. Genes make up the chemical structure carrying the patient's genetic information that may determine human characteristics (i.e., eye color, height and sex). The new gene that is put in the T cells in this study makes a piece of an antibody called anti-CD30. This antibody floats around in the blood and can detect and stick to cancer cells called lymphoma cells because they have a substance on the outside of the cells called CD30. Anti-CD30 antibodies have been used to treat people with lymphoma, but have not been strong enough to cure most patients. For this study, the anti-CD30 antibody has been changed so that instead of floating free in the blood part of it is now joined to the T cells. Only the part of the antibody that sticks to the lymphoma cells is attached to the T cells instead of the entire antibody. When an antibody is joined to a T cell in this way it is called a chimeric receptor. These CD30 chimeric (combination) receptor-activated T cells seem to kill some of the tumor, but they do not last very long in the body and so their chances of fighting the cancer are unknown.

The purpose of this research study is to determine a safe dose of the ATLCAR.CD30 cells that can be given to subjects after undergoing an autologous transplant. This is the first step in determining whether giving ATLCAR.CD30 cells to others with lymphoma in the future will help them. The researchers also want to find out what side effects patients will have after they receive the ATLCAR.CD30 cells post-transplant. This study will also look at other effects of ATLCAR.CD30 cells, including their effect on your cancer and how long they will survive in your body.


Condition or disease Intervention/treatment Phase
Hodgkin Disease Lymphoma Lymphoma, Non-Hodgkin Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Drug: ATLCAR.CD30 cells Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of the Administration of T Lymphocytes Expressing the CD30 Chimeric Antigen Receptor (CAR) for Prevention of Relapse of CD30+ Lymphomas After High Dose Therapy and Autologous Stem Transplantation (ATLAS)
Actual Study Start Date : July 15, 2016
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2034

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: ATLCAR.CD30 cells

Three dose levels of ATLCAR.CD30 cells will be evaluated. Using the modified continual reassessment method (CRM), initial cohort of size two will be enrolled at each dose level after that subjects are enrolled one at a time until a minimum of 12 patients is treated. Each patient will receive one injection according to the dosing schedules listed below. Investigators will start with the lowest cell dose (2X10^7 cells/m^2) given to patients in one of our previous trials employing CAR-T cells including the CD28 costimulatory endodomain, and investigators will escalate the cell dose to the highest cell dose (2X10^8/m^2) given in the same trial.

Note: Initially, only adults will be enrolled during the dose escalation phase of the study. Once a dose level has been tested in at least 2 adults without the occurrence of dose limiting toxicities (DLTs), children may then be enrolled on that dose level according to the CRM.

Drug: ATLCAR.CD30 cells

Three dose levels will be evaluated:

Group One, 2x10^7 cells/m^2 (maximum dose 5x10^7 cells)

Group Two, 1x10^8 cells/m^2 (maximum dose 2.5x10^8 cells)

Group Three, 2x10^8 cells/m^2 (maximum dose 5x10^8 cells)

Other Name: CAR.CD30 T cells




Primary Outcome Measures :
  1. Number of participants with adverse events as a measure of safety and tolerability of escalating doses of autologous activated T lymphocytes [ Time Frame: 6 weeks ]
    Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 4.0) and cytokine release syndrome (CRS) toxicity will be graded according to the toxicity scale outlined in 11.6 (Appendix F: CRS Toxicity Grading Scale and Management Guidelines). The MTD will be based on the rate of dose-limiting toxicity


Secondary Outcome Measures :
  1. To measure the survival of ATLCAR.CD30 in vivo [ Time Frame: 15 years ]
    Persistence of CAR.CD30 T cells in vivo will be determined by quantitative polymerase chain reaction (PCR) and flow cytometry in peripheral blood samples

  2. To estimate PFS after infusion of ATLCAR.CD30 post ASCT in patients with CD30+ lymphoma at high risk for relapse [ Time Frame: 15 years ]
    PFS is defined from day of ASCT to relapse (in subjects with a documented complete response after ASCT) or progression (in subjects with documented stable disease or partial response after ASCT), or death as a result of any cause as per the Revised Response Criteria for Malignant Lymphoma

  3. Determine the overall survival after infusion of ATLCAR.CD30 [ Time Frame: 15 years ]
    Overall survival will be measured from the date of administration of CAR.CD30 transduced ATL to date of death



Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Informed consent explained to, understood by and signed by patient/guardian; patient/guardian given copy of informed consent.
  • 3 to 17 years of age for pediatric patients, ≥18 years of age for adults; NOTE: children will not be allowed to enroll in a dose cohort until a minimum of 2 adult subjects are enrolled and complete their DLT assessment follow-up at that dose level
  • Diagnosis of recurrent HL with a treatment plan that will include high dose chemotherapy with/without total body irradiation and autologous cell transplantation
  • NHL patients with ALK negative CD30+ anaplastic large-cell lymphomas, CD30+ ALCL regardless of ALK status, with chemotherapy-sensitive relapse, CD30+ high-risk DLBCL, CD30+ cutaneous T cell lymphoma, or CD30+ mycosis fungoides who are otherwise eligible for transplant, are eligible for this study
  • CD30+ disease (result can be pending at the time of cell procurement, but must be confirmed prior to treatment with ATLCAR.CD30 cells); NOTE: CD30 + disease is defined as requiring documentation of CD30 expression by immunohistochemistry based on the institutional hematopathology standard.
  • Evidence of adequate organ function as defined by:

    • The following is required prior to procurement (NOTE: labs do not need to be redrawn if they have already been performed as part of SOC pre-transplant work-up; Subject must be eligible to receive ASCT)

      • Hgb ≥ 8.0g/dL
      • Bilirubin ≤1.5 times the upper limit of normal (ULN)
      • AST ≤ 3 times ULN
      • Serum creatinine ≤1.5 times ULN
      • Cardiac and pulmonary function that is adequate for ASCT
    • The following is required prior to infusion of ATLCAR.CD30 cells:

      • Absolute neutrophil count (ANC) ≥500 cells/mm3 for 3 consecutive days; Note: ANC may be measured at the beginning and the end of a time frame expanding at least 3 days and does not need to be evaluated on each individual day AND
      • Platelet count ≥25,000 cells/mm3 without transfusion over preceding 5 days Note: Platelets may be measured at the beginning and the end of a time frame expanding at least 5 days and does not need to be evaluated on each individual day AND
      • Hg ≥8g/dL without transfusion support over preceding 5 days Note: Hg may be measured at the beginning and the end of a time frame expanding at least 3 days and does not need to be evaluated on each individual day
      • Bilirubin ≤1.5 times the upper limit of normal (ULN)
      • AST ≤ 3 times ULN
      • Serum creatinine ≤1.5 times ULN
      • Pulse oximetry of > 90% on room air
  • Imaging results from within 60 days prior to transplant (used as baseline measure for documentation of disease status). Note: Results may be obtained at a time point greater than 30 days from transplant if obtained per the patient's standard of care and with prior sponsor approval.
  • Negative serum pregnancy test within 72 hours prior to procurement and again 72 hours prior to infusion
  • Karnofsky or Lansky score of > 60%
  • Considered at high risk for relapse as defined by: The presence of ≥ 1 of the following: failure to achieve CR post initial treatment; relapsed disease with an initial remission duration of <12 months; or extranodal involvement at the start of pre-transplant salvage therapy
  • Subjects must have autologous transduced activated T cells that meet the Certificate of Analysis (CoA) acceptance criteria
  • Women of childbearing potential (WOCBP) should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study, and for 6 months after the study is concluded. WOCBP are those who have not been surgically sterilized or have not been free from menses for > 1 year. The two birth control methods can be composed of: two barrier methods or a barrier method plus a hormonal method to prevent pregnancy. The male partner of WOCBP subjects enrolled into the trial should be instructed to use a condom by their female partner enrolled in the trial.

Exclusion Criteria:

  • Received any investigational agents or received any tumor vaccines within the previous six weeks prior to cell infusion.
  • Received anti-CD30 antibody-based therapy within the previous 4 weeks prior to cell infusion
  • History of hypersensitivity reactions to murine protein-containing products
  • Pregnant or lactating
  • Tumor in a location where enlargement could cause airway obstruction.
  • Current use of systemic corticosteroids at doses ≥10mg/day prednisone or its equivalent; those receiving <10mg/day may be enrolled at discretion of investigator
  • Active infection with HIV, HTLV, HBV, HCV (can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells) . Active infection is defined as not being well controlled on therapy (Note: To meet eligibility subjects are required to be negative for HIV antibody or HIV viral load, negative for HTLV1 and 2 antibody, negative for Hepatitis B surface antigen, or negative for HCV antibody or HCV viral load).

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): NCT02663297


Contacts
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Contact: Catherine Cheng 919-445-4208 catherine_cheng@med.unc.edu
Contact: Spencer Laing 919-962-8618 spencer.laing@med.unc.edu

Locations
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United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Catherine Cheng    919-445-4208    catherine_cheng@med.unc.edu   
Contact: Spencer Laing    919-962-8618    spencer.laing@med.unc.edu   
Principal Investigator: Thomas Shea, MD         
Wake Forest University Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Rakee Vaidya, M.B.B.S    336-716-2774    ravaidya@wakehealth.edu   
Principal Investigator: Rakee Vaidya, M.B.B.S         
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Thomas Shea, MD Director, Bone Marrow Transplant Program

Additional Information:
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Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT02663297     History of Changes
Other Study ID Numbers: LCCC 1524-ATL
R01HL114564 ( U.S. NIH Grant/Contract )
First Posted: January 26, 2016    Key Record Dates
Last Update Posted: January 29, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
CAR T cells
CD30
Lymphoma
T Lymphocytes

Additional relevant MeSH terms:
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Lymphoma
Disease
Neoplasms
Hodgkin Disease
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Immune System Diseases
Neoplasms by Histologic Type
Lymphatic Diseases
Immunoproliferative Disorders
Pathologic Processes