CD30 CAR-expressing Autologous T Lymphocytes in Preventing Relapse after High Dose Chemotherapy and Stem Cell Transplant in Patients with CD30+ Lymphoma

Status: Active

Description

This phase I trial studies the side effects and best dose of CD30 chimeric antigen receptor (CAR)-expressing autologous T lymphocytes when given after high dose chemotherapy and stem cell transplant to patients with cluster of differentiation (CD)30+ lymphoma. T-cells are special infection fighting blood cells that can kill tumor cells. The T-cells given in this study will come from the patient and will have a new gene put in them that makes an antibody called anti-CD30. This antibody sticks to lymphoma cells because of a substance on the outside of cells called CD30. Attaching anti-CD30 antibody to T-cells may help the T-cells to find cancer cells that have developed a way to hide from the immune system. Giving T-cells with anti-CD30 antibody attached may help restore immune system function and prevent relapse in patients with CD30+ lymphoma that has come back.

Eligibility Criteria

Inclusion Criteria

  • INCLUSION CRITERIA PRIOR TO CELL PROCUREMENT
  • Informed consent explained to, understood by and signed by subject/guardian; subject/guardian given copy of the procurement/screening informed consent
  • 3 to 17 years of age for pediatric subjects, >= 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 were enrolled and complete their dose limiting toxicity (DLT) assessment follow-up at that dose level
  • Diagnosis of recurrent Hodgkin's lymphoma (HL) with a treatment plan that will include high dose chemotherapy with/without total body irradiation and autologous cell transplantation
  • Non-Hodgkin lymphoma (NHL) subjects with anaplastic lymphoma kinase (ALK) negative CD30+ anaplastic large-cell lymphomas (ALCL), CD30+ ALCL regardless of ALK status, with chemotherapy-sensitive relapse, CD30+ high-risk diffuse large B-cell lymphoma (DLBCL), CD30+ cutaneous T cell lymphoma, or CD30+ mycosis fungoides who are otherwise eligible for transplant, are eligible for this study
  • Karnofsky or Lansky score of > 60%
  • Hemoglobin (Hgb) >= 8.0g/dL, required prior to procurement (NOTE: labs do not need to be redrawn if they have already been performed as part of standard of care [SOC] pre-transplant work-up; subject must be eligible to receive ASCT)
  • Bilirubin =< 1.5 times the upper limit of normal (ULN), 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)
  • Aspartate aminotransferases (AST) =< 3 times ULN, 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)
  • Serum creatinine =< 1.5 times ULN, 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)
  • Cardiac and pulmonary function that is adequate for ASCT, 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)
  • In women of child-bearing potential (WOCBP), a negative serum pregnancy test within 72 hours prior to procurement; WOCBP are those who have not been surgically sterilized or have not been free from menses for > 1 year
  • Considered at high risk for relapse as defined by: * The presence of >= 1 of the following: failure to achieve complete response (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
  • 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
  • INCLUSION CRITERIA PRIOR TO CELL INFUSION: Informed consent explained to, understood by and signed by subject/guardian; subject/guardian given copy of informed consent
  • INCLUSION CRITERIA PRIOR TO CELL INFUSION: 3 to 17 years of age for pediatric subjects, >= 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 were enrolled and complete their DLT assessment follow-up at that dose level
  • INCLUSION CRITERIA PRIOR TO CELL INFUSION: Diagnosis of recurrent HL with a treatment plan that will include high dose chemotherapy with/without total body irradiation and autologous cell transplantation
  • INCLUSION CRITERIA PRIOR TO CELL INFUSION: NHL subjects 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
  • INCLUSION CRITERIA PRIOR TO CELL INFUSION: 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 requires documented CD30 expression by immunohistochemistry based on the institutional hematopathology standard
  • INCLUSION CRITERIA PRIOR TO CELL INFUSION: Required prior to infusion of ATLCAR.CD30 cells: Absolute neutrophil count (ANC) >= 500 cells/mm^3 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
  • INCLUSION CRITERIA PRIOR TO CELL INFUSION: Required prior to infusion of ATLCAR.CD30 cells: Platelet count >= 25,000 cells/mm^3 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
  • INCLUSION CRITERIA PRIOR TO CELL INFUSION: Required prior to infusion of ATLCAR.CD30 cells: Hemoglobin (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 5 days and does not need to be evaluated on each individual day
  • INCLUSION CRITERIA PRIOR TO CELL INFUSION: Required prior to infusion of ATLCAR.CD30 cells: Bilirubin =< 1.5 times the upper limit of normal (ULN)
  • INCLUSION CRITERIA PRIOR TO CELL INFUSION: Required prior to infusion of ATLCAR.CD30 cells: AST =< 3 times ULN
  • INCLUSION CRITERIA PRIOR TO CELL INFUSION: Required prior to infusion of ATLCAR.CD30 cells: Serum creatinine =< 1.5 times ULN
  • INCLUSION CRITERIA PRIOR TO CELL INFUSION: Required prior to infusion of ATLCAR.CD30 cells: Pulse oximetry of > 90% on room air
  • INCLUSION CRITERIA PRIOR TO CELL INFUSION: Imaging results from within 60 days prior to transplant (used as baseline measure for documentation of disease status)
  • INCLUSION CRITERIA PRIOR TO CELL INFUSION: In women of child-bearing potential (WOCBP), a negative serum pregnancy test within 72 hours prior to procurement and again 72 hours prior to infusion is required
  • INCLUSION CRITERIA PRIOR TO CELL INFUSION: Karnofsky or Lansky score of > 60%
  • INCLUSION CRITERIA PRIOR TO CELL INFUSION: 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
  • INCLUSION CRITERIA PRIOR TO CELL INFUSION: Subjects must have autologous transduced activated T-cells that meet the Certificate of Analysis (CoA) acceptance criteria
  • INCLUSION CRITERIA PRIOR TO CELL INFUSION: 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
  • 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 may be enrolled at discretion of investigator
  • Active infection with human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), hepatitis B virus (HBV), hepatitis C virus (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)

Locations & Contacts

North Carolina

Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: Active
Contact: Marcie L. Riches
Phone: 919-966-4431
Email: marcie_riches@med.unc.edu
Winston-Salem
Wake Forest University Health Sciences
Status: Active
Contact: Rakhee Vaidya
Phone: 336-716-2774
Email: ravaidya@wakehealth.edu

Trial Objectives and Outline

PRIMARY OBJECTIVE:

I. To determine the safety and tolerability and to estimate the maximum tolerated dose (MTD) of CD30 CAR-expressing autologous T lymphocytes (ATLCAR.CD30) post autologous stem cell transplant (ASCT) in subjects with CD30+ lymphoma at high risk for relapse.

SECONDARY OBJECTIVES:

I. To measure the survival of ATLCAR.CD30 in vivo.

II. To estimate progression free survival (PFS) after infusion of ATLCAR.CD30 post ASCT in subjects with CD30+ lymphoma at high risk for relapse.

III. To determine the overall survival after infusion of ATLCAR.CD30 post ASCT in subjects with CD30+ lymphoma at high risk for relapse.

EXPLORATORY OBJECTIVES:

I. To measure patient-reported symptom, physical function, and health-related quality of life at baseline and over time in patients treated with ATLCAR.CD30 cells.

II. To determine whether there are correlations between CAR T cell behavior and the integration locations of CAR.CD30.

OUTLINE: This is a dose-escalation study.

Patients receive ATLCAR.CD30 intravenously (IV) over 1-10 minutes between 14 and 20 days following standard of care high dose chemotherapy and autologous stem cell transplant.

After completion of study treatment, patients are followed up every 6 months for up to 5 years, then yearly for 10 years.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
UNC Lineberger Comprehensive Cancer Center

Principal Investigator
Marcie L. Riches

Trial IDs

Primary ID LCCC1524-ATL
Secondary IDs NCI-2016-00578
Clinicaltrials.gov ID NCT02663297