CD30 Receptor-Activated T-cells in Treating Patients with Relapsed or Refractory CD30+ Hodgkin Lymphoma or Non-Hodgkin Lymphoma

Status: Active

Description

This phase Ib / II trial studies the side effects of and how well CD30 receptor-activated T-cells work in treating patients with CD30+ Hodgkin lymphoma or non-Hodgkin lymphoma that has come back after a period of treatment or does not respond to treatment. T-cells are special infection fighting blood cells that can kill cancer 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+ Hodgkin lymphoma or non-Hodgkin lymphoma.

Eligibility Criteria

Inclusion Criteria

  • PRIOR TO CELL PROCUREMENT: Informed consent explained to, understood by and signed by the patient or legal guardian for pediatric patients; patient and/or legal guardian given a copy of informed consent form for procurement
  • PRIOR TO CELL PROCUREMENT: For pediatric subjects (weight must be >= 10 kg)
  • PRIOR TO CELL PROCUREMENT: Diagnosis of recurrent HL or NHL in patients who have failed > 2 prior treatment regimens; patients relapsed after autologous or allogeneic stem cell transplant are eligible for this study
  • PRIOR TO CELL PROCUREMENT: 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
  • PRIOR TO CELL PROCUREMENT: Karnofsky or Lansky score of > 60% (Karnofsky for >= 16 years old and Lansky for < 16 years old)
  • PRIOR TO CELL PROCUREMENT: Hemoglobin (Hgb) >= 8.0 g/dL (transfusion independent for 2 weeks prior to enrollment)
  • PRIOR TO CELL PROCUREMENT: Bilirubin =< 1.5 times the upper limit of normal (ULN)
  • PRIOR TO CELL PROCUREMENT: Aspartate aminotransferase (AST) =< 3 times ULN
  • PRIOR TO CELL PROCUREMENT: Serum creatinine =< 1.5 times ULN
  • PRIOR TO CELL PROCUREMENT: For patients < 18 years old use the following table for serum creatinine requirements: * Age (years): Maximum serum creatinine (mg/dL) * 3 to < 6: =< 0.8 (male and female) * 6 to < 10: =< 1.0 (male and female) * 10 to < 13: =< 1.2 (male and female) * 13 to < 16: =< 1.5 (male), =< 1.4 (female) * >= 16 and < 18: =< 1.7 (male), =< 1.4 (female)
  • PRIOR TO CELL PROCUREMENT: Negative serum pregnancy test in females within 72 hours prior to procurement or documentation that the subject is post-menopausal or premenarchal
  • PRIOR TO CELL PROCUREMENT: 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; WOCBP patients will also be instructed to tell their male partners to use a condom * Postmenopausal status must be confirmed with documentation of absence of menses for > 1 year
  • PRIOR TO LYMPHODEPLETION: Informed consent explained to, understood by and signed by the patient or legal guardian for pediatric patients; patient and/or legal guardian given a copy of informed consent form
  • PRIOR TO LYMPHODEPLETION: CD30+ disease (result can be pending at the time of cell procurement, but must be confirmed prior to lymphodepletion); NOTE: CD30+ disease requires documented CD30 expression by immunohistochemistry based on the institutional hematopathology standard
  • PRIOR TO LYMPHODEPLETION: Absolute neutrophil count (ANC) is > 1,000 cells/mm^3
  • PRIOR TO LYMPHODEPLETION: Platelet count > 75,000/mm^3
  • PRIOR TO LYMPHODEPLETION: For grade 4 neutropenia, >= grade 3 febrile neutropenia, or grade 4 thrombocytopenia, hold bendamustine until toxicity resolve to =< grade 2
  • PRIOR TO LYMPHODEPLETION: For WOCBP negative serum pregnancy test within 72 hours prior to lymphodepletion
  • PRIOR TO LYMPHODEPLETION: Imaging results from within 7 days (30 days in subjects with cutaneous T cell lymphoma) prior to lymphodepletion; subjects who have received bridging chemotherapy must have imaging performed at least 3 weeks after most recent therapy (imaging does not need to be repeated if it is within 7 days prior to lymphodepletion)
  • PRIOR TO LYMPHODEPLETION: Karnofsky or Lansky score of > 60% (Karnofsky for pediatric patients ≥ 16 years old and Lansky for < 16 years old)
  • PRIOR TO LYMPHODEPLETION: Available autologous transduced activated T-cells that meet the Certificate of Analysis (CofA) acceptance criteria
  • PRIOR TO LYMPHODEPLETION: 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; WOCBP patients will also be instructed to tell their male partners to use a condom; post-menopausal status must be confirmed with documentation of absence of menses for > 1 year
  • PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Bilirubin =< 1.5 times the upper limit of normal (ULN)
  • PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: AST =< 3 times ULN
  • PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Serum creatinine =< 1.5 times ULN
  • PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Pulse oximetry of > 90% on room air
  • PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: For patients < 18 years old use the following table for serum creatinine requirements: * Age (years): Maximum serum creatinine (mg/dL) * 3 to < 6: =< 0.8 (male and female) * 6 to < 10: =< 1.0 (male and female) * 10 to < 13: =< 1.2 (male and female) * 13 to < 16: =< 1.5 (male), =< 1.4 (female) * >= 16 and < 18: =< 1.7 (male), =< 1.4 (female)
  • PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Karnofsky or Lansky score of > 60% (Karnofsky for ≥ 16 years old and Lansky for < 16 years old)
  • PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: 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; WOCBP patients will also be instructed to tell their male partners to use a condom; post-menopausal status must be confirmed with documentation of absence of menses for > 1 year

Exclusion Criteria

  • PRIOR TO CELL PROCUREMENT: Pregnant or lactating
  • PRIOR TO CELL PROCUREMENT: Tumor in a location where enlargement could cause airway obstruction
  • PRIOR TO CELL PROCUREMENT: Active infection with human immunodeficiency virus (HIV), human T-cell lymphotropic virus (HTLV), 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) defined as not being well controlled on therapy; patients are required to have negative HIV antibody or negative HIV viral load, negative HTLV1 and 2 antibodies, negative HCV antibody or viral load
  • PRIOR TO CELL PROCUREMENT: Subjects who are positive for hepatitis B surface antigen (can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells) are excluded”; subjects who are hepatitis B surface antigen negative but hepatitis B core antibody positive must have their hepatitis B viral load checked; these subjects will be excluded if their viral load is positive at baseline; subjects who are core antibody positive and viral load negative at baseline will be considered eligible
  • PRIOR TO LYMPHODEPLETION: Received any investigational agents or received any tumor vaccines within the previous six weeks prior to cell lymphodepletion
  • PRIOR TO LYMPHODEPLETION: Received anti-CD30 antibody-based therapy within the previous 4 weeks prior to cell lymphodepletion
  • PRIOR TO LYMPHODEPLETION: Received chemotherapy within the previous 3 weeks prior to lymphodepletion
  • PRIOR TO LYMPHODEPLETION: Subject has rapidly progressive disease, per treating oncologist’s discretion
  • PRIOR TO LYMPHODEPLETION: Subject is not a good candidate for CAR-T cell therapy, per treating oncologist’s discretion
  • PRIOR TO LYMPHODEPLETION: Pregnant or lactating
  • PRIOR TO LYMPHODEPLETION: Tumor in a location where enlargement could cause airway obstruction
  • PRIOR TO LYMPHODEPLETION: Current use of systemic corticosteroids at doses equivalent of >= 10 mg prednisone daily or its equivalent; those receiving < 10 mg daily may be enrolled at discretion of investigator; inhaled steroids are allowed * For pediatric patients, physiologic replacement hydrocortisone at doses 6-12 mg/m^2/day is allowed; equivalently dosed alternative steroids are allowed at discretion of investigator, though not to exceed 10mg prednisone per day; inhaled steroids are allowed
  • PRIOR TO LYMPHODEPLETION: Patients on strong inhibitors of CYP1A2 (e.g., fluvoxamine, ciprofloxacin) as these may increase plasma concentrations of bendamustine, and decrease plasma concentrations of its metabolites
  • PRIOR TO LYMPHODEPLETION: Active infection with HIV, HTLV, 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) defined as not being well controlled on therapy; patients are required to have negative HIV antibody or negative HIV viral load, negative HTLV1 and 2 antibodies, negative HCV antibody or viral load
  • PRIOR TO LYMPHODEPLETION: Patients who are positive for hepatitis B surface antigen are excluded; patients who are hepatitis B surface antigen negative but hepatitis B core antibody positive must have their hepatitis B viral load checked; these subjects will be excluded if their viral load is positive at baseline; subjects who are core antibody positive and viral load negative at baseline will be considered eligible if the subject has initiated an anti-HBV prophylaxis regimen prior to lymphodepletion
  • PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Received any investigational agents or received any tumor vaccines within the previous six weeks prior to cell infusion
  • PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Received anti-CD30 antibody-based therapy within the previous 4 weeks prior to cell infusion
  • PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Tumor in a location where enlargement could cause airway obstruction
  • PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Subject has rapidly progressive disease, per treating oncologist’s discretion
  • PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Subject is not a good candidate for CAR-T cell therapy, per treating oncologist’s discretion
  • PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Current use of systemic corticosteroids at doses ≥ 10 mg prednisone daily or its equivalent; those receiving < 10 mg daily may be enrolled at discretion of investigator; inhaled steroids are allowed * For pediatric patients, physiologic replacement hydrocortisone at doses 6-12mg/m^2/day is allowed; equivalently dosed alternative steroids are allowed at discretion of investigator, though not to exceed 10mg prednisone per day; inhaled steroids are allowed
  • PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Active infection with HIV, HTLV, 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) defined as not being well controlled on therapy; patients are required to have negative HIV antibody or negative HIV viral load, negative HTLV1 and 2 antibodies, negative HCV antibody or viral load
  • PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Patients who are positive for hepatitis B surface antigen are excluded; patients who are hepatitis B surface antigen negative but hepatitis B core antibody positive must have their hepatitis B viral load checked; these subjects will be excluded if their viral load is positive at baseline; subjects who are core antibody positive and viral load negative at baseline will be considered eligible; these subjects must be receiving antiviral prophylaxis initiated prior to lymphodepletion
  • PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Subject must not be pregnant or lactating

Locations & Contacts

North Carolina

Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: Active
Contact: Anne Wood Beaven
Phone: 919-966-9268
Email: beaven@med.unc.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To establish a safe dose (i.e., number cells/m^2) of CD30 chimeric antigen receptor (CAR)-expressing autologous T lymphocytes (ATLCAR.CD30) to infuse after lymphodepletion with bendamustine in adult patients with CD30+ refractory/relapsed Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL). (Phase Ib)

II. To establish a safe dose (ie, number cells/m^2) of ATLCAR.CD30 to infuse after lymphodepletion with bendamustine and fludarabine in pediatric patients with CD30+ refractory/relapsed Hodgkin lymphoma (HL) and non-Hodgkin's lymphoma (NHL). (Phase Ib)

III. To estimate 2 year progression free survival (PFS) after administration of ATLCAR.CD30 in combined adult/pediatric patients with CD30+ refractory/relapsed HL and NHL. (Phase II)

SECONDARY OBJECTIVES:

I. To estimate 2 year overall survival (OS) after administration of CAR.CD30 transduced autologous T lymphocytes (ATL) following lymphodepletion with bendamustine in adult patients with CD30+ relapsed/refractory HL and NHL.

II. To estimate 2 year OS after administration of CAR.CD30 transduced ATL following lymphodepletion with bendamustine and fludarabine in adult and pediatric patients with CD30+ relapsed/refractory HL and NHL.

III. To estimate 2 year PFS after administration of ATLCAR.CD30 following lymphodepletion with bendamustine in adult patients with CD30+ refractory/relapsed HL and NHL.

IV. To estimate 2 year PFS after administration of ATLCAR.CD30 following lymphodepletion with bendamustine and fludarabine in adult and pediatric patients with CD30+ refractory/relapsed HL and NHL.

V. To estimate the objective response rate as defined by the Lugano classification for CAR.CD30 transduced ATL following lymphodepletion with bendamustine when administered in adult patients with CD30+ relapsed/refractory HL and NHL.

VI. To estimate the objective response rate as defined by the Lugano classification for CAR.CD30 transduced ATL following lymphodepletion with bendamustine and fludarabine when administered in adult and pediatric patients with CD30+ relapsed/refractory HL and NHL.

VII. To estimate duration of response after administration of CAR.CD30 transduced ATL following lymphodepletion with bendamustine in adult patients with CD30+ relapsed/refractory HL and NHL.

VIII. To estimate duration of response after administration of CAR.CD30 transduced ATL following lymphodepletion with benamustine and fludarabine in adult and pediatric patients with CD30+ relapsed/refractory HL and NHL.

IX. To further describe the adverse events associated with CAR.CD30 transduced ATL when administered in adult and pediatric patients with CD30+ relapsed/refractory HL and NHL.

X. To evaluate the safety of bendamustine alone or combined with fludarabine as lymphodepleting agents prior to infusion of CAR.CD30 transduced ATL in adult patients.

XI. To evaluate the safety of bendamustine and fludarabine as lymphodepleting agents prior to infusion of CAR.CD30 transduced ATLs in pediatric patients.

XII. To measure the survival of ATLCAR.CD30 in vivo when infused after lymphodepletion with bendamustine.

XIII. To measure the survival of ATLCAR.CD30 in vivo when infused after lymphodepletion with bendamustine and fludarabine.

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

EXPLORATORY OBJECTIVES:

I. Estimate PFS in adult and pediatric patients separately who have received lymphodepletion with bendamustine and fludarabine prior to administration of CAR.CD30 transduced ATL.

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 of CD30 CAR-expressing autologous T lymphocytes, followed by a phase II study.

Beginning on day -60, patients may receive standard of care treatment comprising bendamustine intravenously (IV) over 10 minutes on days 1-2 every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity or other standard of care treatment per physician’s discretion.

LYMPHODEPLETING CHEMOTHERAPY: Patients receive bendamustine IV and fludarabine IV over 3 consecutive days.

T-CELL INFUSION: Patients receive CD30 CAR-expressing autologous T lymphocytes IV over 1-10 minutes 1-4 days after lymphodepleting chemotherapy for a total of 2 doses. Patients achieving a partial response or stable disease at 6 weeks, may receive a second infusion of CD30 CAR-expressing autologous T lymphocytes if available.

After completion of study treatment, patients are followed up on day 1 of weeks 1, 2, 3, 4, 6, and day 1 of months 3, 6, 9, and 12, and then every 6 months for 4 years, and yearly for up to 15 years.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
UNC Lineberger Comprehensive Cancer Center

Principal Investigator
Anne Wood Beaven

Trial IDs

Primary ID LCCC1532-ATL
Secondary IDs NCI-2016-00789
Clinicaltrials.gov ID NCT02690545