Description:
The body has different ways of fighting infection and disease. No single way is 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 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 with bacteria or viruses. 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
treat cancer. This study will combine both T cells and antibodies in order to create a more
effective treatment called Autologous T Lymphocyte Chimeric Antigen Receptor cells targeted
against the CD30 antigen (ATLCAR.CD30). Another treatment being tested includes the
Autologous T Lymphocyte Chimeric Antigen Receptor cells targeted against the CD30 antigen
with CCR4 (ATLCAR.CD30.CCR4) to help the cells move to regions in the patient's body where
the cancer is present. Participants in this study will receive either ATLCAR.CD30.CCR4 cells
alone or will receive ATLCAR.CD30.CCR4 cells combined with ATLCAR.CD30 cells.
Previous studies have shown that a new gene can be put into T cells that will increase their
ability to recognize and kill cancer cells. The new gene that is put in the T cells in this
study makes an antibody called anti-CD30. This antibody sticks to lymphoma cells because of 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 instead of floating free in the blood it is
now joined to the T cells. 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 (ATLCAR.CD30)
can 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.
Researchers are working to identify ways to improve the ability of ATLCAR.CD30 to destroy
tumor cells. T cells naturally produce a protein called CCR4 which functions as a navigation
system directing T cells toward tumor cells specifically. In this study, researchers will
also genetically modify ATLCAR.CD30 cells to produce more CCR4 proteins and they will be
called ATLCAR.CD30.CCR4. The study team believes that the ATLCAR.CD30.CCR4 cells will be
guided directly toward the tumor cells based on their navigation system. In addition, the
study team believes the majority of ATLCAR.CD30 cells will also be guided directly toward
tumor cells when given together with ATLCAR.CD30.CCR4, increasing their anti-cancer fighting
ability.
This is the first time ATLCAR>CD30.CCR4 cells or combination of ATLCAR.CD30.CCR4 and
ATLCAR.CD30 cells are used to treat lymphoma. The purpose of this study to determine the
following:
- What is the safe dose of ATLCAR.CD30.CCR4 cells to give to patients
- What is the safe dose of the combination of ATLCAR.CD30 and ATLCAR.CD30.CCR4 cells to
give to patients
Title
- Brief Title: Study of CAR-T Cells Expressing CD30 and CCR4 for r/r CD30+ HL and CTCL
- Official Title: Phase I Study of the Administration of T Lymphocytes Co-Expressing the CD30 Chimeric Antigen Receptor (CAR) and CCR4 for Relapsed/Refractory CD30+ Hodgkin Lymphoma and Cutaneous T-Cell Lymphoma
Clinical Trial IDs
- ORG STUDY ID:
LCCC 1606-ATL
- NCT ID:
NCT03602157
Conditions
- Lymphoma
- Immune System Diseases
- Immunoproliferative Disorders
- Lymphatic Diseases
- Lymphoproliferative Disorders
- Neoplasms
- Cutaneous Lymphoma
- Cutaneous Anaplastic Large Cell Lymphoma
- Mycosis Fungoides
- Sezary Syndrome
- Lymphomatoid Papulosis
- Cutaneous T Cell Lymphoma
- Gray Zone Lymphoma
Interventions
Drug | Synonyms | Arms |
---|
ATLCAR.CD30.CCR4 cells | | ATLCAR.CD30.CCR4 & ATLCAR.CD30 |
ALTCAR.CD30 cells | | ATLCAR.CD30.CCR4 & ATLCAR.CD30 |
Bendamustine | | ATLCAR.CD30.CCR4 & ATLCAR.CD30 |
Fludarabine | | ATLCAR.CD30.CCR4 & ATLCAR.CD30 |
Purpose
The body has different ways of fighting infection and disease. No single way is 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 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 with bacteria or viruses. 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
treat cancer. This study will combine both T cells and antibodies in order to create a more
effective treatment called Autologous T Lymphocyte Chimeric Antigen Receptor cells targeted
against the CD30 antigen (ATLCAR.CD30). Another treatment being tested includes the
Autologous T Lymphocyte Chimeric Antigen Receptor cells targeted against the CD30 antigen
with CCR4 (ATLCAR.CD30.CCR4) to help the cells move to regions in the patient's body where
the cancer is present. Participants in this study will receive either ATLCAR.CD30.CCR4 cells
alone or will receive ATLCAR.CD30.CCR4 cells combined with ATLCAR.CD30 cells.
Previous studies have shown that a new gene can be put into T cells that will increase their
ability to recognize and kill cancer cells. The new gene that is put in the T cells in this
study makes an antibody called anti-CD30. This antibody sticks to lymphoma cells because of 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 instead of floating free in the blood it is
now joined to the T cells. 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 (ATLCAR.CD30)
can 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.
Researchers are working to identify ways to improve the ability of ATLCAR.CD30 to destroy
tumor cells. T cells naturally produce a protein called CCR4 which functions as a navigation
system directing T cells toward tumor cells specifically. In this study, researchers will
also genetically modify ATLCAR.CD30 cells to produce more CCR4 proteins and they will be
called ATLCAR.CD30.CCR4. The study team believes that the ATLCAR.CD30.CCR4 cells will be
guided directly toward the tumor cells based on their navigation system. In addition, the
study team believes the majority of ATLCAR.CD30 cells will also be guided directly toward
tumor cells when given together with ATLCAR.CD30.CCR4, increasing their anti-cancer fighting
ability.
This is the first time ATLCAR>CD30.CCR4 cells or combination of ATLCAR.CD30.CCR4 and
ATLCAR.CD30 cells are used to treat lymphoma. The purpose of this study to determine the
following:
- What is the safe dose of ATLCAR.CD30.CCR4 cells to give to patients
- What is the safe dose of the combination of ATLCAR.CD30 and ATLCAR.CD30.CCR4 cells to
give to patients
Detailed Description
This study is a single center, open-label Phase I clinical trial designed to determine the
safety of escalating doses of autologous activated T lymphocytes (ATLs) co-expressing the
chimeric antigen receptor specific for the CD30 antigen and the CCR4 chemokine receptor
(ATLCAR.CD30.CCR4) in subjects with relapsed/refractory CD30+ Hodgkin (HL) and cutaneous T
Cell Lymphoma (CTCL). Subjects with grey zone lymphoma will also be eligible to enroll on
this protocol; the characteristics of grey zone lymphoma are very similar to HL and therefore
will be referred to collectively throughout the protocol under the general term of HL.
Subjects will receive either ATLCAR.CD30.CCR4 or the ATLCAR.CD30.CCR4 product in combination
with an ATL product encoding only the CAR.CD30 (ATLCAR.CD30). The dose for ATLCAR.CD30 will
be fixed at the highest dose level as this product has been shown to be safe in phase I
trials with and without lymphodepletion. Six total dose levels of ATLCAR.CD30.CCR4 with or
without ATLCAR.CD30 will be tested. Prior to receiving the infusions, subjects will undergo
lymphodepletion with bendamustine and fludarabine, The 3+3 design will be used for estimating
the maximum tolerated dose (MTD) of ATLCAR.CD30.CCR4 in combination with ATLCAR.CD30. Any
dose level may be expanded to 4-9 subjects to explore adverse events (AEs) of special
interest prior to moving to the next dose level. If due to the expansion ≥1/3 of the total
number of subject on that dose level experiences a DLT, the study would not escalate to the
next highest dose level and the maximum tolerated dose would be exceeded. The final MTD will
be the highest dose of ATLCAR.CD30.CCR4 and ATLCAR.CD30 with observed DLT rate of less than
1/3. An expansion cohort will enroll up to 8 subjects at the MTD of ATLCAR.CD30.CCR4 and
ATLCAR.CD30 to further assess safety and efficacy of these cellular products. Secondary
endpoints include evaluation of persistence of ATLCAR.CD30.CCR4 vs. ATLCAR.CD30 in the
peripheral blood, accumulation of ATLCAR.CD30.CCR4 vs. ATLCAR.CD30 in tumor biopsies, and
progression free survival (PFS).
LCCC1606-ATL builds on LCCC1532-ATL, a phase Ib/II trial investigating the safety and
efficacy of ATLCAR.CD30 in subjects with CD30+ lymphoma.
OUTLINE
Cell Procurement
Up to 300 mL total of peripheral blood will be obtained (in up to 3 collections) from
subjects for cell procurement. Up to 300 mL total of peripheral blood will be obtained (in up
to 3 collections) from subjects for cell procurement. Additionally, leukapheresis may be
performed to isolate sufficient cells in subjects with a low absolute lymphocyte count or who
had inadequate peripheral blood collection. The parameters for apheresis will be up to 2
blood volumes. Collected peripheral blood may be used for generation of CAR-T cells if the
cells were collected on another CAR-T cell trial for which Lineberger Comprehensive Cancer
Center is the sponsor and if the subject is eligible for procurement/screening on the LCCC
1606-ATL protocol. ATLCAR.CD30 cells manufactured for a different protocol may be used for
LCCC 1606-ATL, if they fit specifications for the protocol and the patient qualifies for the
protocol.
Lymphodepletion Regimen
In order to receive lymphodepletion and CAR-T cells, subjects must still have evidence of
active disease.
All subjects will receive lymphodepletion with bendamustine 70 mg/m2 and fludarabine 30 mg/m2
for 3 days to reduce possible toxicity associated with the agent prior to administration of
CAR-T cells.
NOTE: Any subject who tests positive for Hepatitis B core antibody and negative for Hepatitis
B viral load during screening must initiate an anti-Hepatitis B prophylaxis regimen prior to
lymphodepletion.
Bendamustine and fludarabine will be administered concomitantly for lymphodepletion (i.e.,
intravenous (IV) administration of bendamustine 70 mg/m2/day over 3 consecutive days and IV
fludarabine 30 mg/m2/day over 3 consecutive days) prior to the first CAR-T cell infusion.
Bendamustine should be administered first followed by IV administration of fludarabine.
Cell Administration
ATLCAR.CD30.CCR4 with or without ATLCAR.CD30 cells will be given to eligible subjects 2-14
days (preferably 2-4 days) after lymphodepletion with fludarabine and bendamustine. The dose
of cells will vary, depending on the cohort enrolled. The cells will be administered by a
licensed provider (oncology nurse or physician) via intravenous injection over 1-10 minutes
through either a peripheral or a central line. The expected volume will be 1-50cc. Subjects
in the dose expansion part of the study who received the highest safe dose level of
ATLCAR.CD30 and ATLCAR.CD30.CCR4 may receive a second infusion of ATLCAR.CD30 and
ATLCAR.CD30.CCR4 if cells are available equal to the dose administered for the first cell
infusion (or a lower dose).
Duration of Therapy
Therapy in LCCC1606-ATL involves one to two infusion(s) of ATLCAR.CD30.CCR4 with or without
ATLCAR.CD30 cells. Treatment with one infusion will be administered unless:
- Subject decides to withdraw from study treatment, OR
- General or specific changes in the subject's condition render the subject unacceptable
for further treatment in the judgment of the investigator.
Duration of Follow-up
Subjects who receive a cell infusion will be followed for up to 15 years for replication
competent retrovirus (RCR) evaluation or until death, whichever occurs first. Subjects who
are removed from study and do not receive the cellular therapy product due to unacceptable
adverse events will be followed until resolution or stabilization of the adverse event.
Subjects who have progressive disease or initiate another cancer therapy after receiving a
cell infusion(s) will still be required to complete abbreviated follow up procedures.
Trial Arms
Name | Type | Description | Interventions |
---|
ATLCAR.CD30.CCR4 & ATLCAR.CD30 | Experimental | A 3+3 design in adult subjects. Subjects in the first dose level will receive ATLCAR.CD30.CCR4 cells alone, once safety has been established, the initial dose of ATLCAR.CD30.CCR4 will be combined with a fixed dose of ATLCAR.CD30 cells in the next dose level. Every time the dose of ATLCAR.CD30.CCR4 is escalated, subjects in that dose level will receive ATLCAR.CD30.CCR4 alone prior to subsequent dose level enrolling subjects to receive a combination of fixed dose ATLCAR.CD30 and the selected dose level of ATLCAR.CD30.CCR4. The six dose levels will consist of: dose level 1 = 2 × 10^7 ATLCAR.CD30.CCR4 cells/m2; dose level 2 = 1 × 10^8 ATLCAR.CD30 cells/m2 and 2 × 10^7 ATLCAR.CD30.CCR4 cells/m2; dose level 3 = 5 × 10^7/m2 ATLCAR.CD30.CCR4 cells/m2; dose level 4 = 1 × 10^8 ATLCAR.CD30 cells/m2 and 5 × 10^7 ATLCAR.CD30.CCR4 cells/m2; dose level 5 = 1 × 10^8/m2 ATLCAR.CD30.CCR4 cells/m2; dose level 6 = 1 × 108 ATLCAR.CD30 cells/m2 and 1 × 108 ATLCAR.CD30.CCR4 cells/m2. | - ATLCAR.CD30.CCR4 cells
- ALTCAR.CD30 cells
- Bendamustine
- Fludarabine
|
Eligibility Criteria
Inclusion Criteria
- Unless otherwise noted, subjects must meet all of the following criteria to
participate in this study:
- Written informed consent and HIPAA authorization for release of personal health
information. Subjects or their Legally Authorized Representative must sign a consent
to undergo cell procurement. Written informed consent to enroll in the CAR T-cell
therapy trial must be obtained prior to lymphodepletion.
- Adults ≥18 years of age.
- Subjects must have one of the following diagnoses by WHO criteria:
- Classic Hodgkin Lymphoma
- Mycosis fungoides
- Sezary syndrome
- Primary cutaneous CD30 positive T cell lymphoproliferative disorder including
lymphomatoid papulosis or primary cutaneous anaplastic large cell lymphoma
- B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and
classic Hodgkin Lymphoma (Grey Zone Lymphoma)
- Diagnosis of recurrent lymphoma in subjects who have failed ≥2 prior treatment
regimens.
- These prior treatment regimens must include brentuximab vedotin.
- If the subject has Hodgkin Lymphoma, the subject must have either failed autologous
transplant or must not be eligible for autologous transplant.
- If the subject has grey zone lymphoma, the subject must have failed an anthracycline
containing regimen unless the subject was not previously a candidate for anthracycline
- Subjects relapsed after autologous or allogeneic stem cell 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.CCR4 and ATLCAR.CD30 cells); NOTE: CD30+
disease requires documented CD30 expression by immunohistochemistry based on the
institutional hematopathology standard.
- Karnofsky score of > 60%
- For Subjects in the Expansion Cohort: Willing to undergo biopsy following the cell
infusion. A biopsy may be required (i.e., considered mandatory) in subjects receiving
both cellular products if the Investigator determines the tumor site is easily
accessible (e.g., palpable tumor). If the Investigator feels that the biopsy would be
difficult to obtain or poses a high degree of risk to the subject, it may be deferred.
- Women of childbearing potential (WOCBP) must 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 subjects will also be instructed to tell
their male partners to use a condom.
Exclusion Criteria
- Subjects meeting any of the following exclusion criteria will not be able to
participate in this study:
- Pregnant or lactating.
- Tumor in a location where enlargement could cause airway obstruction.
- Current use of systemic corticosteroids at doses ≥10mg prednisone daily or its
equivalent; those receiving <10mg daily may be enrolled at discretion of the
Investigator.
- 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. Subjects are
required to have negative HIV antibody, negative HTLV1 and 2 antibody, and negative
HCV antibody or viral load.
- Active infection with HBV. Subjects are required to have a negative Hepatitis B
surface Antigen. In addition, subjects must either have core antibody negative HBV
(results can be pending at the time of cell procurement) OR if a subject is Hepatitis
B core antibody positive they 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.
- Has a known additional malignancy that is active and/or progressive requiring
treatment; exceptions include basal cell or squamous cell skin cancer, in situ
cervical or bladder cancer, or other cancer for which the subject has been
disease-free for at least three years.
- A history of intolerance to fludarabine. Subjects with an intolerance to bendamustine
may be allowed to enroll at the discretion of the clinical investigator if he/she
thinks that the subject is a candidate for lymphodepletion with cyclophosphamide and
fludarabine.
- Subject is not a good candidate for treatment with ATLCAR.CD30.CCR4 with and without
ATLCAR.CD30 per Investigator's discretion.
Eligibility criteria to be met prior to procurement
Evidence of adequate organ function as defined by:
The following is required prior to procurement:
- Hgb ≥ 8.0g/dL (transfusion independent for 2 weeks prior to enrollment)
- Bilirubin ≤1.5 times the upper limit of normal (ULN). Subjects with Gilbert's syndrome
may be enrolled despite a total bilirubin level >1.5 mg/dL if their conjugated
bilirubin is <1.5× ULN
- AST ≤ 3 times ULN
- Serum creatinine ≤1.5 times ULN.
- Creatinine Clearance (CrCl) >60mL/min per Cockcroft and Gault
- Pulse oximetry of >90% on room air
- Imaging results from within 120 days prior to procurement to assess presence of active
disease (no tumor imaging is required prior to procurement for participants with
active cutaneous lymphoma).
- Negative serum pregnancy test within 72 hours prior to procurement or documentation
that the subject is post-menopausal. Post-menopausal status must be confirmed with
documentation of absence of menses for > 1 year, or documentation of surgical
menopause involving bilateral oophorectomy.
- Subject has no clinical indication of rapidly progressing disease in opinion of
treating physician.
- Subject has adequate cardiac function, defined as:
- No ECG evidence of acute ischemia
- No ECG evidence of active, clinically significant conduction system abnormalities
- Prior to study entry, any ECG abnormality at screening not felt to put the
subject at risk has to be documented by the Investigator as not medically
significant
- No uncontrolled angina or severe ventricular arrhythmias
- No clinically significant pericardial disease
- No history of myocardial infarction within the last 6 months prior to infusion
- No Class 3 or higher New York Heart Association Congestive Heart Failure
Eligibility criteria to be met prior to lymphodepletion
- Presence of active disease. Imaging results from within 7 days prior to
lymphodepletion to confirm presence of active disease. 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).
Evidence of adequate organ function as defined by:
The following are required prior to lymphodepletion:
- Adequate bone marrow function (ANC>1000 cells/mm3 and platelets >75,000/mm3). Subjects
cannot have received platelet transfusion within 7 days of lymphodepletion.
- Bilirubin ≤1.5 times the upper limit of normal (ULN). Subjects with Gilbert's syndrome
may be enrolled despite a total bilirubin level >1.5 mg/dL if their conjugated
bilirubin is <1.5× ULN)
- AST ≤ 3 times ULN
- Serum creatinine ≤1.5 times ULN.
- Creatinine Clearance (CrCl) >60mL/min per Cockcroft and Gault
- Pulse oximetry of > 90% on room air
- Negative serum pregnancy test within 72 hours prior to lymphodepletion or
documentation that the subject is post-menopausal. Post-menopausal status must be
confirmed with documentation of absence of menses for > 1 year or documentation of
surgical menopause involving bilateral oophorectomy.
- Subjects must have autologous transduced activated T-cells that meet the Certificate
of Analysis (CofA) acceptance criteria.
- Has not received any investigational agents or received any tumor vaccines within the
previous six weeks prior to lymphodepletion.
- Has not received anti-CD30 antibody-based therapy within the previous 4 weeks prior to
lymphodepletion.
- Has not received chemotherapy or radiation therapy within the previous 3 weeks prior
to lymphodepletion.
Subjects cannot be on strong inhibitors of CYP1A2 (e.g., fluvoxamine, ciprofloxacin) as
these may increase plasma concentrations of bendamustine, and decrease plasma
concentrations of its metabolites. See http://medicine.iupui.edu/clinpharm/ddis/ for an
updated list of strong inhibitors of CYP1A2. (This applies to subjects who receive
bendamustine for lymphodepletion (required) up through 72 hours after the last dose of
bendamustine).
- Subjects who are HBV core antibody positive and HBV viral load negative prior to
lymphodepletion must have initiated anti-HBV prophylaxis prior to lymphodepletion.
- Subject has no clinical indication of rapidly progressing disease in the opinion of
the treating physician.
- Subject is a good candidate for treatment with ATLCAR.CD30.CCR4 with and without
ATLCAR.CD30 per the investigator's discretion.
Eligibility criteria to be met prior to cell infusion after lymphodepletion
- No evidence of uncontrolled infection or sepsis.
Evidence of adequate organ function as defined by:
1. Bilirubin ≤2 times the upper limit of normal (ULN) unless attributed to Gilbert's
syndrome
2. AST ≤3 times ULN
3. ALT ≤3 times ULN
4. Creatinine Clearance (CrCl) >60mL/min per Cockcroft and Gault
5. Pulse oximetry of >90% on room air
- Subject has no clinical indication of rapidly progressing disease in the opinion
of the treating physician.
- Subject is a good candidate for treatment with ATLCAR.CD30.CCR4 with and without
ATLCAR.CD30 per the investigator's discretion.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of participants with adverse events (AE) as a measure of safety and tolerability ATLCAR.CD30.CCR4 and ATLCAR.CD30 cells |
Time Frame: | 6 weeks |
Safety Issue: | |
Description: | Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0), CRS toxicity will be graded according to the toxicity scale outlined in CRS Grading Criteria/Link to CRS Management Guidelines and ICANS will be graded according to the toxicity scale outlined in Management of Neurotoxicity/Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) from CAR-T Therapy. The MTD will be based on the rate of dose-limiting toxicity. |
Secondary Outcome Measures
Measure: | Median progression free survival (PFS) after infusion of ATLCAR.CD30.CCR4 with and without ATLCAR.CD30 in subjects with CD30+ relapsed/refractory HL and CTCL. |
Time Frame: | 15 years |
Safety Issue: | |
Description: | PFS is defined from day of ATLCAR.CD30.CCR4 with and without ATLCAR.CD30 infusion to relapse (in subjects in a documented complete response prior to conditioning chemotherapy) or progression (in subjects not in a complete response prior to conditioning chemotherapy), or death as a result of any cause |
Measure: | Median overall survival (OS) in subjects with CD30+ relapsed/refractory HL and CTCL after administration of ATLCAR.CD30.CCR4 with and without ATLCAR.CD30 |
Time Frame: | 15 years |
Safety Issue: | |
Description: | Overall survival will be measured from the date of administration of ATLCAR.CD30.CCR4 with and without ATLCAR.CD30 infusion to date of death |
Measure: | Objective response rate by 7 weeks and best overall response rate in subjects with CD30+ relapsed/refractory HL and CTCL after infusion of ATLCAR.CD30.CCR4 with and without ATLCAR.CD30 |
Time Frame: | 7 weeks |
Safety Issue: | |
Description: | The objective response rate will be defined as the rate of complete responses (CR) + partial responses (PR) by 7 weeks post ATLCAR.CD30.CCR4 with and without ATLCAR.CD30 infusion |
Measure: | Differential infiltration of ATLCAR.CD30.CCR4 vs. ATLCAR.CD30 cells in tumor biopsies in subjects who received both ATLCAR.CD30.CCR4 and ATLCAR.CD30 cellular products |
Time Frame: | 15 years |
Safety Issue: | |
Description: | Differential infiltration of ATLCAR.CD30.CCR4 vs. ATLCAR.CD30 cells in tumor biopsies in subjects receiving both ATLCAR.CD30.CCR4 and ATLCAR.CD30 cellular products will be determined by measuring the level of the transgene and by phenotypic analyses |
Measure: | Persistence of ATLCAR.CD30.CCR4 vs. ATLCAR.CD30 in peripheral blood in subjects who received both ATLCAR.CD30.CCR4 and ATLCAR.CD30 cellular products |
Time Frame: | 15 years |
Safety Issue: | |
Description: | Persistence of ATLCAR.CD30.CCR4 and ATLCAR.CD30 cells in peripheral blood will be determined by quantitative polymerase chain reaction (PCR) and flow cytometry in samples of peripheral blood in subjects who received infusion of both ATLCAR.CD30.CCR4 and ATLCAR.CD30 cellular products |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | UNC Lineberger Comprehensive Cancer Center |
Trial Keywords
- CAR T cells
- CD30
- CCR4
- Lymphoma
- T lymphocytes
Last Updated
July 7, 2021