Study of CD30 CAR for Relapsed/Refractory CD30+ HL and CD30+ NHL
- Conditions
- Lymphoma, Non-HodgkinLymphomaImmune System DiseasesImmunoproliferative DisordersLymphatic DiseasesLymphoproliferative DisordersNeoplasmsNeoplasms by Histologic Type
- Interventions
- Registration Number
- NCT02690545
- Lead Sponsor
- 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 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. 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 that 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 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 establish a safe dose of ATLCAR.CD30 cells to infuse after lymphodepleting chemotherapy and to estimate the number patients whose cancer does not progress for two years after ATLCAR.CD30 administration. This study will also look at other effects of ATLCAR.CD30 cells, including their effect on the patient's cancer.
- Detailed Description
STUDY OBJECTIVES
Primary Objective (Phase Ib portion of Study) To establish a safe dose (ie, number cells/m2) of ATLCAR.CD30 to infuse after lymphodepletion with bendamustine in adult patients with CD30+ refractory/relapsed Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).
To establish a safe dose (ie, number cells/m2) of ATLCAR.CD30 to infuse after lymphodepletion with bendamustine and fludarabine in pediatric patients with CD30+ refractory/relapsed Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).
Primary Objective (Phase II portion of study) 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
Secondary Objectives
To estimate 2 year overall survival (OS) after administration of CAR.CD30 transduced ATL following lymphodepletion with bendamustine in adult patients with CD30+ relapsed/refractory HL and NHL.
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.
To estimate 2 year PFS after administration of ATLCAR.CD30 following lymphodepletion with bendamustine in adult patients with CD30+ refractory/relapsed HL and NHL.
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.
To estimate the objective response rate as defined by the Lugano Classification78 for CAR.CD30 transduced ATL following lymphodepletion with bendamustine when administered in adult patients with CD30+ relapsed/refractory HL and NHL.
To estimate the objective response rate as defined by the Lugano Classification78 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.
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
To estimate duration of response 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
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.
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.
To evaluate the safety of bendamustine and fludarabine as lymphodepleting agents prior to infusion of CAR.CD30 transduced ATLs in pediatric patients.
To measure the survival of ATLCAR.CD30 in vivo when infused after lymphodepletion with bendamustine.
To measure the survival of ATLCAR.CD30 in vivo when infused after lymphodepletion with bendamustine and fludarabine.
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.
Primary Endpoint (Phase Ib)
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 CRS Management Guidelines and CRS Toxicity Grading Scale
Primary Endpoint (Phase II)
PFS is defined from day of ATLCAR.CD30 infusion to relapse (in patients with a documented complete response at time of cell infusion) or progression (in patients without complete response at time of cell infusion), or death as a result of any cause per the Lugano classification
Secondary Endpoints
Overall survival will be measured from the date of administration of CAR.CD30 transduced ATL to date of death and will be measured separately in subjects receiving bendamustine alone for lymphodepletion and those receiving a combination of bendamustine and fludarabine for lymphodepletion.
Progression free survival is defined from day of ATLCAR.CD30 infusion to relapse (in patients with a documented complete response at time of cell infusion) or progression (in patients without complete response at time of cell infusion), or death as a result of any cause per the Lugano classification78 and will be measured separately in subjects receiving bendamustine alone for lymphodepletion and those receiving a combination of bendamustine and fludarabine for lymphodepletion.
The objective response rate will be defined as the rate of complete responses (CR) + partial responses (PR) as determined by the Lugano classification78 and will be measured separately in subjects receiving bendamustine alone for lymphodepletion and those receiving a combination of bendamustine and fludarabine for lymphodepletion.
The duration of response will be defined as time from documentation of tumor response to disease progression and will be measured separately in subjects receiving bendamustine alone for lymphodepletion and those receiving a combination of bendamustine and fludarabine for lymphodepletion.
Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 4.0). S
Persistence of CAR.CD30 T cells in vivo will be determined by quantitative PCR and flow cytometry in peripheral blood samples and will be measured separately in subjects receiving bendamustine alone for lymphodepletion and those receiving a combination of bendamustine and fludarabine for lymphodepletion.
For adult patients: Patient reported symptoms will be measured using selected symptoms from the NCI PRO-CTCAE. Patient-reported physical function will be measured using the PROMIS Physical Function Score derived from the PROMIS Physical Function Short Form 20a v1.0. Patient-reported health-related quality of life will be measured using the PROMIS Global Health Score derived from the PROMIS Global Health Short Form v1.0-1.1.
OUTLINE
Cell Procurement
Up to 100 mL per collection (up to 3 collections) of peripheral blood will be obtained from patients for cell procurement. In patients with low (CD3 count as assayed by flow cytometry less than 200/μl) T-cell count in the peripheral blood, a leukopheresis may be performed to isolate sufficient T cells. The parameters for pheresis will be 2 blood volumes.
ATLCAR.CD30 Cells Administration
ATLCAR.CD30 cells will be administered as described below 1-14 days (preferably 1-2 days) after lymphodepletion with bendamustine and fludarabine. ATLCAR.CD30 cells will be given 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. Patients with a partial response or stable disease at 6 weeks may receive a second infusion of ATLCAR.CD30 if cells are available. Note: Lymphodepletion with bendamustine and fludarabine will occur for three consecutive days and may be given prior to a second infusion of cells (if applicable).
Duration of Therapy
Therapy in Lineberger Comprehensive Cancer Center (LCCC) 1532 involves 1-2 infusions of ATLCAR.CD30 cells. Treatment with one infusion will be administered unless:
* Patient decides to withdraw from study treatment, OR
* General or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator.
Duration of Follow-up
Patients will be followed for up to 15 years for Replication Competent Retrovirus (RCR) evaluation or until death, whichever occurs first. Patients removed from study for unacceptable adverse events will be followed until resolution or stabilization of the adverse event.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 40
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ATLCAR.CD30 cells ATLCAR.CD30 cells Phase Ib: In adults, and separately, in children, two doses will be investigated 1x10\^8 cells/m2 and 2x10\^8 cells/m\^2. The study team will run two independent dose-escalation sequences, one for adults and another one for children. The study team plans to use the 3+3 design and start with a low dose of 1x10\^8 cells/m2. If there are no DLT in first 3 patients, the study team will go up to the dose of 2 x 10\^8 cells/m2. If there is toxicity in 1/3 patients in the initial cohort, the study team would expand to enroll up to 6 patients. If there are dose limiting toxicities (DLT) at the dose of 2 x 10\^8 cells/m\^2, the study team will initially decrease the dose to an intermediate dose of 1.5 x 10\^8 cells/m\^. Phase II: The study team planning to enroll 31 patients to contribute data. Sequential boundary will be used to monitor DLT rate.
- Primary Outcome Measures
Name Time Method Number of participants with adverse events as a measure of safety and tolerability of ATLCAR.CD30 cells to establish a safe dose after lymphodepletion with bendamustine in adult patients 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). Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE
Number of participants with adverse events as a measure of safety and tolerability of ATLCAR.CD30 cells to establish a safe dose after lymphodepletion after lymphodepletion with bendamustine and fludarabine in pediatric patients 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). Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE
2 year progression free survival (PFS) after administration of ATLCAR.CD30 in combined adult/pediatric patients with CD30+ refractory/relapsed HL and NHL. 2 years PFS is defined from day of ATLCAR.CD30 infusion to relapse (in patients with a documented complete response at time of cell infusion) or progression (in patients without complete response at time of cell infusion), or death as a results of any cause per the Lugano classification.
- Secondary Outcome Measures
Name Time Method 2 year overall survival (OS) after administration of ATLCAR.CD30 transduced ATl following lymphodepletion with bendamustine in adult patients with CD30+ refractory/relapsed HL and NHL 2 years Overall survival will be measured from the date of administration of CAR.CD30 transduced ATL to date of death and will be measured in subjects receiving bendamustine alone.
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. 6 weeks The objective response rate will be defined as the rate of complete responses (CR) + partial responses (PR) as determined by the Lugano classification and will be measured in subjects receiving bendamustine and fludarabine for lymphodepletion.
Adverse events associated with CAR.CD30 transduced ATL when administered in adult and pediatric patients with CD30+ relapsed/refractory HL and NHL. 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).
2 year overall survival (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. 2 years Overall survival will be measured from the date of administration of CAR.CD30 transduced ATL to the date of death and will be measured in subjects receiving a combination of bendamustine and fludarabine for lymphodepletion.
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 6 weeks The objective response rate will be defined as the rate of complete responses (CR) + partial responses (PR) as determined by the Lugano classification and will be measured in subjects receiving bendamustine alone for lymphodepletion.
2 year progression free survival after administration of ATLCAR.CD30 following lymphodepletion with bendamustine in adult patients with CD30+ in adult patients with CD30+ refractory/relapsed HL and NHL. 2 years Progression free survival is defined from day of ATLCAR.CD30 infusion to relapse (in patients with a documented complete response at time of cell infusion) or progression (in patients without complete response at time of cell infusion), or death as a result of any cause per the Lugano classification and will be measured in subjects receiving bendamustine alone.
2 year progression free survival after administration of ATLCAR.CD30 following lymphodepletion with bendamustine and fludarabine in adult and pediatric patients with CD30+ refractory/relapsed HL and NHL. 2 years Progression free survival is defined from day of ATLCAR.CD30 infusion to relapse (in patients with a documented complete response at time of cell infusion) or progression (in patients without complete response at time of cell infusion), or death as a result of any cause per the Lugano classification and will be measured in subjects receiving a combination of bendamustine and fludarabine for lymphodepletion.
Duration of response after administration of CAR.CD30 transduced ATL following lymphodepletion with bendamustine in adult patients with CD30+ relapsed/refractory HL and NHL. 15 years Duration of response will be defined as time from documentation of tumor response to disease progression and will be measured in subjects receiving bendamustine alone for lymphodepletion.
Duration of response 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. 15 years Duration of response will be defined as time from documentation of tumor response to disease progression and will be measured in subjects receiving a combination of bendamustine and fludarabine for lymphodepletion.
Number of participants with adverse events as a measure of safety and tolerability of bendamustine and fludarabine as lymphodepleting agents 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).
Survival of ATLCAR.CD30 in vivo when infused after lymphodepletion with bendamustine. 15 years Persistence of CAR.CD30 T cells in vivo will be determined by quantitative PCR and flow cytometry in peripheral blood samples and will be measured in subjects receiving bendamustine alone for lymphodepletion.
Measure patient reported quality of life using the PROMIS Physical Function (PROMIS Physical Function SF20a) at baseline and over time in adult patients treated with CAR.CD30 T cells. 15 years The PROMIS Physical Function short form is a 20 item instrument that measures self-reported capability rather than actual performance of physical activities. This includes the functioning of one's upper extremities (dexterity), lower extremities (walking or mobility), and central regions (neck, back), as well as instrumental activities of daily living, such as running errands. Each item has five response options ranging in value from 1 (unable to do) to 5 (without any difficulty). To items are summed to find the overall raw score.
Number of adverse events as a measure of safety and tolerability of bendamustine and fludarabine as lymphodepleting agents prior to infusion of CAR.CD30 transduced ATLs in pediatric patients. 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).
Measure patient-reported symptoms using selected symptom items from the NCI Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) at baseline and over time in adult patients treated with CAR.CD30 T cells. 15 years The NCI Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) is a patient-reported outcome measurement system developed to characterize the frequency, severity and interference of 78 symptomatic treatment toxicities. Each item is scored from 0 to four.
Measure patient-reported quality of life using the PROMIS Global Health (PROMIS GHS SF v1.0-1.1) at baseline and over time in adult patients treated with CAR.CD30 T cells. 15 years The PROMIS Global Health Short Form is a 10-item instrument representing multiple domains relating to overall health. Each item has a scale from 1 (poor) to 5 (excellent). Item 7, 8, and 10 are recoded. The global physical health score is generated by summing responses to Global03, Global06, Global07 rescored, Global08 rescored. The Global Mental Health score is generated by summing responses to Global02, Global04, Global05, Global10 Rescored.
To measure the survival of ATLCAR.CD30 in vivo when infused after lymphodepletion with bendamustine and fludarabine. 15 years Persistence of CAR.CD30 T cells in vivo will be determined by quantitative PCR and flow cytometry in peripheral blood samples and will be measured in subjects receiving bendamustine in combination with fludarabine for lymphodepletion
Trial Locations
- Locations (1)
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States