Description:
Background:
- Improved treatments for a variety of treatment-resistant, CD30-expressing malignancies
including Hodgkin lymphoma, anaplastic large cell lymphoma, and other CD30- expressing
lymphomas are needed.
- T cells can be genetically modified to express chimeric antigen receptors (CARs) that
specifically target malignancy-associated antigens.
- Autologous T cells genetically modified to express CARs targeting the B-cell antigen
CD19 have caused complete remissions in a small number of patients with lymphoma. These
results demonstrate that CAR-expressing T cells can have anti-lymphoma activity in
humans.
- CD30 expression can be easily detected by immunohistochemistry on lymphoma cells, which
allows selection of CD30-expressing malignancies for treatment.
- CD30 is not known to be expressed by normal cells except for a small number of activated
lymphocytes.
- We have constructed a novel fully-human anti-CD30 CAR that can specifically recognize
CD30-expressing target cells in vitro and eradicate CD30-expressing tumors in mice.
- This particular CAR has not been tested before in humans.
- Possible toxicities include cytokine-associated toxicities such as fever, hypotension,
and neurological toxicities. Elimination of a small number of normal activated
lymphocytes is possible, and unknown toxicities are also possible.
Objectives:
Primary
-Determine the safety and feasibility of administering T-cells expressing a novel fullyhuman
anti-CD30 CAR to patients with advanced CD30-expresssing lymphomas.
Eligibility:
- Patients must have anaplastic large cell lymphoma, peripheral T-cell lymphoma not
otherwise specified, diffuse large B-cell lymphoma not otherwise specified, primary
mediastinal B-cell lymphoma, grey zone lymphoma, enteropathyassociated T-cell lymphoma,
or extranodal NK/T-cell lymphoma, nasal type
- Patients must have malignancy that is both measurable on a CT scan with a largest
diameter of at least 1.5 cm and possessing increased metabolic activity detectable by
PET scan. Alternatively patients with lymphoma detected by flow cytometry of bone marrow
are eligible.
- Patients must have a creatinine of 1.6 mg/dL or less and a normal cardiac ejection
fraction.
- An ECOG performance status of 0-2 is required.
- No active infections are allowed including evidence of active HIV, hepatitis B, or
hepatitis C. At the time of protocol enrollment patients must be seronegative for CMV by
antibody testing or must have a negative blood CMV PCR.
- Absolute neutrophil count greater than or equal to 1000/micro L, platelet count greater
than or equal to 55,000/micro L, hemoglobin greater than or equal to 8g/dL
- Serum ALT and AST less or equal to 3 times the upper limit of the institutional normal
unless liver involvement by malignancy is demonstrated.
- At least 14 days must elapse between the time of any prior systemic treatment (including
corticosteroids above 5 mg/day of prednisone or equivalent corticosteroid dose) and
initiation of required leukapheresis.
- Clear CD30 expression must be detected on 75% or more of malignant cells from either
bone marrow or lymphoma mass by flow cytometry or immunohistochemistry. The patient s
malignancy will need to be assessed for CD30 expression by flow cytometry or
immunohistochemistry performed at the NIH. If unstained, paraffin-embedded bone marrow
or lymphoma sections are available from prior biopsies, these can be used to determine
CD30 expression by immunohistochemistry; otherwise, patients will need to come to the
NIH for a biopsy to determine CD30 expression. The sample for CD30 expression can come
from a biopsy obtained at any time before enrollment, unless the patient has received a
prior anti-CD30 monoclonal antibody, in which case the sample must come from a biopsy
following completion of the most recent anti-CD30 monoclonal antibody treatment.
- Eligible patients with diffuse large B-cell lymphoma or primary mediastinal B-cell
lymphoma must have received 2 prior treatment regimens at least 1 of which included an
anthracycline and an anti-CD20 monoclonal antibody.
- Patients who have never had an allogeneic hematopoietic stem cell transplant as well as
patients who have had a 9/10 or 10/10 HLA-matched sibling or a 9/10 or 10/10 HLA-
matched unrelated donor hematopoietic stem cell transplant are potentially eligible.
- Women who are pregnant or plan to become pregnant will be excluded.
Design:
- This is a phase I dose-escalation trial.
- Patients will undergo leukapheresis.
- T cells obtained by leukapheresis will be genetically modified to express an anti-CD30
CAR.
- Patients will receive a lymphocyte-depleting chemotherapy conditioning regimen with the
intent of enhancing the activity of the infused anti-CD30 CAR-expressing T cells.
- The ch...
Title
- Brief Title: T Cells Expressing a Fully-Human Anti-CD30 Chimeric Antigen Receptor for Treating CD30-Expressing Lymphomas
- Official Title: Anti-CD30 CAR T Cells With Fully-human Binding Domains for Treating CD30-expressing Lymphomas Including Anaplastic Large Cell Lymphomas
Clinical Trial IDs
- ORG STUDY ID:
170048
- SECONDARY ID:
17-C-0048
- NCT ID:
NCT03049449
Conditions
- Lymphoma, Large-Cell, Anaplasitc
- Enteropathy-Associated T-Cell Lymphoma
- Lymphoma, Large B-Cell, Diffuse
- Lymphoma, Extranodal NK-T-Cell
- Lymphoma, T-Cell, Peripheral
Interventions
Drug | Synonyms | Arms |
---|
Anti-CD30-CAR T cells | | 1 |
Cyclophosphamide | | 1 |
Fludarabine | | 1 |
Purpose
Background:
- Improved treatments for a variety of treatment-resistant, CD30-expressing malignancies
including Hodgkin lymphoma, anaplastic large cell lymphoma, and other CD30- expressing
lymphomas are needed.
- T cells can be genetically modified to express chimeric antigen receptors (CARs) that
specifically target malignancy-associated antigens.
- Autologous T cells genetically modified to express CARs targeting the B-cell antigen
CD19 have caused complete remissions in a small number of patients with lymphoma. These
results demonstrate that CAR-expressing T cells can have anti-lymphoma activity in
humans.
- CD30 expression can be easily detected by immunohistochemistry on lymphoma cells, which
allows selection of CD30-expressing malignancies for treatment.
- CD30 is not known to be expressed by normal cells except for a small number of activated
lymphocytes.
- We have constructed a novel fully-human anti-CD30 CAR that can specifically recognize
CD30-expressing target cells in vitro and eradicate CD30-expressing tumors in mice.
- This particular CAR has not been tested before in humans.
- Possible toxicities include cytokine-associated toxicities such as fever, hypotension,
and neurological toxicities. Elimination of a small number of normal activated
lymphocytes is possible, and unknown toxicities are also possible.
Objectives:
Primary
-Determine the safety and feasibility of administering T-cells expressing a novel fullyhuman
anti-CD30 CAR to patients with advanced CD30-expresssing lymphomas.
Eligibility:
- Patients must have anaplastic large cell lymphoma, peripheral T-cell lymphoma not
otherwise specified, diffuse large B-cell lymphoma not otherwise specified, primary
mediastinal B-cell lymphoma, grey zone lymphoma, enteropathyassociated T-cell lymphoma,
or extranodal NK/T-cell lymphoma, nasal type
- Patients must have malignancy that is both measurable on a CT scan with a largest
diameter of at least 1.5 cm and possessing increased metabolic activity detectable by
PET scan. Alternatively patients with lymphoma detected by flow cytometry of bone marrow
are eligible.
- Patients must have a creatinine of 1.6 mg/dL or less and a normal cardiac ejection
fraction.
- An ECOG performance status of 0-2 is required.
- No active infections are allowed including evidence of active HIV, hepatitis B, or
hepatitis C. At the time of protocol enrollment patients must be seronegative for CMV by
antibody testing or must have a negative blood CMV PCR.
- Absolute neutrophil count greater than or equal to 1000/micro L, platelet count greater
than or equal to 55,000/micro L, hemoglobin greater than or equal to 8g/dL
- Serum ALT and AST less or equal to 3 times the upper limit of the institutional normal
unless liver involvement by malignancy is demonstrated.
- At least 14 days must elapse between the time of any prior systemic treatment (including
corticosteroids above 5 mg/day of prednisone or equivalent corticosteroid dose) and
initiation of required leukapheresis.
- Clear CD30 expression must be detected on 75% or more of malignant cells from either
bone marrow or lymphoma mass by flow cytometry or immunohistochemistry. The patient s
malignancy will need to be assessed for CD30 expression by flow cytometry or
immunohistochemistry performed at the NIH. If unstained, paraffin-embedded bone marrow
or lymphoma sections are available from prior biopsies, these can be used to determine
CD30 expression by immunohistochemistry; otherwise, patients will need to come to the
NIH for a biopsy to determine CD30 expression. The sample for CD30 expression can come
from a biopsy obtained at any time before enrollment, unless the patient has received a
prior anti-CD30 monoclonal antibody, in which case the sample must come from a biopsy
following completion of the most recent anti-CD30 monoclonal antibody treatment.
- Eligible patients with diffuse large B-cell lymphoma or primary mediastinal B-cell
lymphoma must have received 2 prior treatment regimens at least 1 of which included an
anthracycline and an anti-CD20 monoclonal antibody.
- Patients who have never had an allogeneic hematopoietic stem cell transplant as well as
patients who have had a 9/10 or 10/10 HLA-matched sibling or a 9/10 or 10/10 HLA-
matched unrelated donor hematopoietic stem cell transplant are potentially eligible.
- Women who are pregnant or plan to become pregnant will be excluded.
Design:
- This is a phase I dose-escalation trial.
- Patients will undergo leukapheresis.
- T cells obtained by leukapheresis will be genetically modified to express an anti-CD30
CAR.
- Patients will receive a lymphocyte-depleting chemotherapy conditioning regimen with the
intent of enhancing the activity of the infused anti-CD30 CAR-expressing T cells.
- The ch...
Detailed Description
Background:
- Improved treatments for a variety of treatment-resistant, CD30-expressing malignancies
including Hodgkin lymphoma, anaplastic large cell lymphoma, and other CD30- expressing
lymphomas are needed.
- T cells can be genetically modified to express chimeric antigen receptors (CARs) that
specifically target malignancy-associated antigens.
- Autologous T cells genetically modified to express CARs targeting the B-cell antigen
CD19 have caused complete remissions in a small number of patients with lymphoma. These
results demonstrate that CAR-expressing T cells can have anti-lymphoma activity in
humans.
- CD30 expression can be easily detected by immunohistochemistry on lymphoma cells, which
allows selection of CD30-expressing malignancies for treatment.
- CD30 is not known to be expressed by normal cells except for a small number of activated
lymphocytes.
- We have constructed a novel fully-human anti-CD30 CAR that can specifically recognize
CD30-expressing target cells in vitro and eradicate CD30-expressing tumors in mice.
- This particular CAR has not been tested before in humans.
- Possible toxicities include cytokine-associated toxicities such as fever, hypotension,
and neurological toxicities. Elimination of a small number of normal activated
lymphocytes is possible, and unknown toxicities are also possible.
Objectives:
Primary
-Determine the safety and feasibility of administering T-cells expressing a novel fullyhuman
anti-CD30 CAR to patients with advanced CD30-expresssing lymphomas.
Eligibility:
- Patients must have anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma,
peripheral T-cell lymphoma not otherwise specified, diffuse large B-cell lymphoma not
otherwise specified, primary mediastinal B-cell lymphoma, grey zone lymphoma,
enteropathy-associated T-cell lymphoma, or extranodal NK/T-cell lymphoma, nasal type
- Patients must have malignancy that is both measurable on a CT scan with a largest
diameter of at least 1.5 cm and possessing increased metabolic activity detectable by
PET scan. Alternatively patients with lymphoma detected by flow cytometry of bone marrow
are eligible.
- Patients must have a creatinine of 1.6 mg/dL or less and a normal cardiac ejection
fraction.
- An ECOG performance status of 0-2 is required.
- No active infections are allowed including evidence of active HIV, hepatitis B, or
hepatitis C. At the time of protocol enrollment, patients must be seronegative for CMV
by antibody testing or must have a negative blood CMV PCR.
- Absolute neutrophil count greater than or equal to 1000/micro L, platelet count greater
than or equal to 55,000/micro L, hemoglobin greater than or equal to 8g/dL
- Serum ALT and AST less or equal to 3 times the upper limit of the institutional normal
unless liver involvement by malignancy is demonstrated.
- At least 14 days must elapse between the time of any prior systemic treatment (including
corticosteroids above 5 mg/day of prednisone or equivalent corticosteroid dose) and
initiation of required leukapheresis.
- Clear CD30 expression must be detected on 75% or more of malignant cells from either
bone marrow or lymphoma mass by flow cytometry or immunohistochemistry. The patient s
malignancy will need to be assessed for CD30 expression by flow cytometry or
immunohistochemistry performed at the NIH. If unstained, paraffin-embedded bone marrow
or lymphoma sections are available from prior biopsies, these can be used to determine
CD30 expression by immunohistochemistry; otherwise, patients will need to come to the
NIH for a biopsy to determine CD30 expression. The sample for CD30 expression can come
from a biopsy obtained at any time before enrollment, unless the patient has received a
prior anti-CD30 monoclonal antibody, in which case the sample must come from a biopsy
following completion of the most recent anti-CD30 monoclonal antibody treatment.
- Eligible patients with diffuse large B-cell lymphoma or primary mediastinal B-cell
lymphoma must have received 2 prior treatment regimens at least 1 of which included an
anthracycline and an anti-CD20 monoclonal antibody.
- Patients who have never had an allogeneic hematopoietic stem cell transplant as well as
patients who have had a 9/10 or 10/10 HLA-matched sibling or a 9/10 or 10/10 HLA-
matched unrelated donor hematopoietic stem cell transplant are potentially eligible.
- Women who are pregnant or plan to become pregnant will be excluded.
Design:
- This is a phase I dose-escalation trial.
- Patients will undergo leukapheresis.
- T cells obtained by leukapheresis will be genetically modified to express an anti-CD30
CAR.
- Patients will receive a lymphocyte-depleting chemotherapy conditioning regimen with the
intent of enhancing the activity of the infused anti-CD30 CAR-expressing T cells.
- A chemotherapy conditioning regimen of cyclophosphamide and fludarabine will be
administered prior to all CAR T-Cell infusions. Fludarabine will be given on the same
days as the cyclophosphamide.
- Two days after the chemotherapy ends, patients will receive an infusion of
anti-CD30-CAR-expressing T cells.
- The initial dose level of this dose-escalation trial will be 0.3x10(6) CAR+ T cells/kg
of recipient bodyweight for Cohort 1. The initial dose level will be 1 x 10 (6) CAR+T
cells/kg for Cohort 2.
- The cell dose administered will be escalated until a maximum tolerated dose is
determined.
- Following the T-cell infusion, there is a mandatory 9-day inpatient hospitalization to
monitor for toxicity.
- Outpatient follow-up is planned for 2 weeks and 1, 2, 3, 4, 6, 9, and 12 months after
the CAR T-cell infusion. Long-term gene-therapy follow-up consisting of yearly visits to
a doctor near the patient s home for 4 more years and then yearly telephone contact for
10 additional years will be required.
- As of Amendment E (Protocol version: 08/03/2018), repeat treatments consisting of the
conditioning chemotherapy followed by a CAR T-cell infusion at the MTD for the patient s
cohort are allowed for eligible patients with any best responses except continuing
complete remission or progressive malignancy.
- Re-enrollment will be allowed for a small number of subjects.
Trial Arms
Name | Type | Description | Interventions |
---|
1 | Experimental | All patients will be receiving starting dose: 0.3x106 CAR+ T cells/kg (weight based dosing)(up to a maximum dose of 18x106 CAR+ T cells /kg)infuse on day 0 and Cyclophosphamide: 300 or 500 mg/m2 IV infusion over 30 minutes on days -5, -4 and -3 and Fludarabine: 30 mg/m2 IV infusion over 30 minutes administered immediately following the cyclophosphamid on days -5, -4,and -3 | - Anti-CD30-CAR T cells
- Cyclophosphamide
- Fludarabine
|
Eligibility Criteria
- INCLUSION CRITERIA:
Malignancy Criteria:
- Patients must have anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma,
peripheral T-cell lymphoma not otherwise specified, diffuse large B-cell lymphoma not
otherwise specified, primary mediastinal B-cell lymphoma, grey zone lymphoma,
enteropathy-associated T-cell lymphoma, or extranodal NK/T-cell lymphoma, nasal type
- Clear CD30 expression must be detected on 75% or more of malignant cells from either
bone marrow or lymphoma mass by flow cytometry or immunohistochemistry. The patient s
malignancy will need to be assessed for CD30 expression by flow cytometry or
immunohistochemistry performed at the NIH. If unstained, paraffin-embedded bone marrow
or lymphoma sections are available from prior biopsies, these can be used to determine
CD30 expression by immunohistochemistry; otherwise, patients will need to come to the
NIH for a biopsy to determine CD30 expression. The sample for CD30 expression can come
from a biopsy obtained at any time before enrollment, unless the patient has received
a prior anti-CD30 monoclonal antibody, in which case the sample must come from a
biopsy following completion of the most recent anti-CD30 monoclonal antibody
treatment.
- Eligible patients with diffuse large B-cell lymphoma or primary mediastinal B-cell
lymphoma must have received 2 prior treatment regimens at least 1 of which included an
anthracycline and an anti-CD20 monoclonal antibody.
- Patients must have measurable malignancy as defined by at least one of the criteria
below.
- Lymphoma mass that is measurable (minimum 1.5 cm in largest diameter) by CT scan is
required unless bone marrow lymphoma is detectable.
- For a lymphoma mass to count as measurable malignancy, it must have abnormally
increased metabolic activity when assessed by positron emission tomography (PET) scan.
- For lymphoma with only bone marrow involvement, no mass is necessary, but if a mass is
not present, bone marrow malignancy must be detectable by flow cytometry.
Other Inclusion Criteria:
- Greater than or equal to 18 years of age and less than or equal to age 73.
- Able to understand and sign the Informed Consent Document.
- Clinical performance status of ECOG 0-2
- Room air oxygen saturation of 92% or greater
- Male patients and must be willing to practice birth control from the time of
enrollment on this study and for four months following the final CAR T-cell infusion.
Pre-menopausal patients (female patients who have had a menstrual period within the
last year) must be willing to practice birth control from the time of enrollment and
for one year following the final CAR T cell infusion.
- Seronegative for HIV antibody. (The experimental treatment being evaluated in this
protocol depends on an intact immune system. Patients who are HIV seropositive can
have decreased immune -competence and thus are less responsive to the experimental
treatment and more susceptible to its toxicities.)
- Seronegative for HTLV-1.
- Negative for hepatitis B surface antigen. Positive hepatitis B tests can be further
evaluated by confirmatory tests; and if confirmatory tests are negative, the patient
can be enrolled.
- Seronegative for hepatitis C antibody unless antigen negative. If hepatitis C antibody
test is positive, then patients must be tested for the presence of RNA by RT-PCR and
be HCV RNA negative to be enrolled.
- A patient with a prior history of hepatits B or a prior history of hepatitis C may
participate, as long as the patient s viral hepatitis has been treated, and the
patient has no detectable HBV DNA or HCV RNA.
- At time of protocol enrollment, the patient should be negative for CMV by antibody
testing or by PCR. In case of disagreement between these 2 CMV tests, the tests will
be repeated and Dept. of Laboratory Medicine consulted.
- Absolute neutrophil count greater than or equal to 1000/mm3 without the support of
filgrastim or other growth factors.
- Platelet count greater than or equal to 55,000/mm3
- Hemoglobin greater than 8.0 g/dl. Transfusion support is allowed.
- Less than 5% malignant cells in the peripheral blood leukocytes
- Serum ALT and AST less or equal to 3 times the upper limit of the institutional normal
unless liver involvement by malignancy is demonstrated.
- Serum creatinine less than or equal to 1.6 mg/dL.
- Total bilirubin less than or equal to 2.0 mg/dl.
- At least 14 days must have elapsed since any prior systemic therapy prior to apheresis
and prior to the initiation of chemotherapy (including systemic corticosteroids at
doses greater than prednisone 5 mg/day or the equivalent corticosteroid doses).
Because this protocol requires collection of autologous blood cells by leukapheresis
in order to prepare CAR T cells, systemic anti-malignancy therapy including systemic
corticosteroid therapy at doses greater than prednisone 5 mg/day or the equivalent
corticosteroid doses is not allowed within 14 days prior to the required
leukapheresis. NOTE: Because of the long half-life and potential to affect CAR
T-cells, 30 days must elapse from the time of administration of anti-PD-1 or
anti-PD-L1 antibodies or other agents that in the opinion of the PI can stimulate
immune activity and infusion of CAR T-cells.
- Normal cardiac ejection fraction (greater than or equal to 50% by echocardiography)
and no evidence of hemodynamically significant pericardial effusion as determined by
an echocardiogram within 4 weeks of the start of the treatment protocol.
- Patients must not take corticosteroids at doses higher than 5 mg/day of prednisone or
the equivalent for 14 days before apheresis, and for 14 days prior to the conditioning
chemotherapy regimen.
- Patients must be willing to undergo endotracheal intubation, mechanical ventilation,
dialysis, CPR, and electrical defibrillation. Patients must be willing to receive
vasopressor drugs and all other standard intensive care unit interventions. Any living
will must be amended to allow these interventions or the patient will not eligible.
- Patients who have been treated on other protocols of genetically-modified T-cells at
the NIH only are potentially eligible under these conditions:
- At least 6 months have elapsed since the last genetically-modified T-cell therapy
that the patient received and there is no evidence of replication-competent
retroviruses (evidence must be provided from prior NIH gene-therapy protocol
Principal Investigator) and persisting genetically-modified T cells are not
detectable in the patient s blood (evidence must be provided by prior NIH
gene-therapy protocol Principal Investigator).
Additional Inclusion Criteria Pertinent Only for Patients with Prior Allogeneic
Transplantation:
- Recipients must have received an 9/10 or 10/10 HLA-matched sibling allogeneic
hematopoietic stem cell transplant, or a 9/10 or 10/10 HLA-matched unrelated donor
(URD) allo-HSCT for an eligible CD30+ lymphoma.
- Donor T cell engraftment after allo-HSCT (>90% donor chimerism of the T-cell
compartment).
- Patients must be at least 90 days post-transplant.
- Patients must be off all systemic immunosuppressive drugs including corticosteroids at
doses of greater than 5 mg/day prednisone or equivalent, if given for treatment of
graft versus host disease, for at least 28 days prior to protocol enrollment and must
remain off immunosuppressive drugs while enrolled on the protocol. Patients must not
be taking any systemic steroids at doses greater than 5 mg/day prednisone or
equivalent at all for 14 days prior to apheresis and initiation of chemotherapy.
Topical corticosteroid preparations applied to the skin such as solutions, creams, and
ointments are allowed. Inhaled corticosteroids are allowed, and corticosteroid eye
drops are allowed.
- Prior DLIs are not necessary.
- Either no evidence of GVHD or minimal clinical evidence of acute GVHD and chronic GVHD
while off of systemic immunosuppressive therapy for at least 28 days. Minimal clinical
evidence of acute GVHD defined as grade 0 to I acute GVHD 109 Minimal evidence of
chronic GVHD is defined as mild global score chronic GVHD (as defined by the 2005 NIH
consensus project) or no chronic GVHD .107 Subjects with disease that is controlled to
stage I acute GVHD or to mild global score chronic GVHD with local topical cutaneous
steroids will be eligible for enrollment.
EXCLUSION CRITERIA:
- Patients with Hodgkin lymphoma are no longer eligible for participation (as of
amendment G, Protocol version: 08/12/2019).
- Patients that require urgent therapy due to tumor mass effects or spinal cord
compression.
- Patients with lymphoma masses 10.0 cm or larger in longest diameter will not be
eligible.
- Patients that have active hemolytic anemia.
- Patients who are currently taking any medications for systemic anticoagulation other
than aspirin will not be eligible.
- Patients with second malignancies in addition to their lymphoma are not eligible if
the second malignancy has required treatment (including maintenance therapy) within
the past 4 years or is not in complete remission. There are two exceptions to this
criterion:
successfully treated non-metastatic basal cell or squamous cell skin carcinoma.
- Women of child-bearing potential who are pregnant or breastfeeding because of the
potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
Women of child-bearing potential are defined as all women except women who are
postmenopausal or who have had a hysterectomy. Postmenopausal will be defined as women
over the age of 55 who have not had a menstrual period in at least 1 year.
- Active uncontrolled systemic infections (defined as infections causing fevers and
infections requiring intravenous antibiotics when the intravenous antibiotics have
been administered for less than 72 hours); active coagulation disorders or other major
uncontrolled medical illnesses of the cardiovascular, respiratory, endocrine, renal,
gastrointestinal, genitourinary or immune system; history of myocardial infarction;
history of idiopathic ventricular tachycardia or ventricular fibrillation in the past
12 months or history of ventricular tachycardia or ventricular fibrillation (VT/VF)
associated with VT/VF risk factors (e.g., QT prolongation and cardiomyopathy); active
cardiac arrhythmias (Active atrial fibrillation is not allowed, but resolved atrial
fibrillation is allowed.); active obstructive or restrictive pulmonary disease; or
active autoimmune diseases such as rheumatoid arthritis.
- Patients will not be seen for screening appointments or enrolled on the protocol if
they have been hospitalized within the 7 days prior to the screening appointment or
the date of protocol enrollment.
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency
Disease) , unless the immunodeficiency has been cured by allogeneic stem cell
transplant.
- Systemic corticosteroid therapy at doses greater than 5 mg/day of prednisone or the
equivalent dose is not allowed within 14 days prior to the required leukapheresis, or
the initiation of the conditioning chemotherapy regimen. Corticosteroid creams,
ointments, and eye drops are allowed.
- History of severe immediate hypersensitivity reaction to any of the agents used in
this study.
- Patients with current CNS involvement by malignancy (either by imaging or
cerebrospinal fluid involvement or biopsy-proven).
- Patients currently taking anticoagulants.
Maximum Eligible Age: | 73 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Determine the safety and feasibility of administering T cells expressing a novel fully-human anti-CD30 CAR to patients with advanced CD30-expresssing lymphomas. |
Time Frame: | 4-5 weeks after first dose |
Safety Issue: | |
Description: | List of adverse event frequency |
Secondary Outcome Measures
Measure: | Assess the immunogenicity of the CAR used in this protocol |
Time Frame: | 5 years |
Safety Issue: | |
Description: | Amount of anti-CD30-CAR transduced T cells in the blood of patients after infusion. |
Measure: | Evaluate the in vivo persistence and peak blood levels of anti-CD30 CAR T cells after initial and repeated CAR T-cell infusions |
Time Frame: | 5 years |
Safety Issue: | |
Description: | Amount of anti-CD30-CAR transduced T cells in the blood of patients after infusion. |
Measure: | Assess for evidence of antilymphoma activity by anti-CD30 CAR T cells |
Time Frame: | 5 years |
Safety Issue: | |
Description: | Evidence of anti-lymphoma activity in the blood after anti-CD30 infusion |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | National Cancer Institute (NCI) |
Trial Keywords
- Gray Zone Lymphoma
- Immunotherapy
- Peripheral T-Cell Lymphoma
- Anaplastic Large Cell Lymphoma
- Angioimmunoblastic T-cell lymphoma
Last Updated
August 20, 2021