- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01626495
Phase I/IIA Study of CART19 Cells for Patients With Chemotherapy Resistant or Refractory CD19+ Leukemia and Lymphoma (Pedi CART19)
CHP 959 - A Phase I/IIA Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCRzeta and 4-1BB Signaling Domains in Patients With Chemotherapy Resistant Or Refractory CD19+ Leukemia and Lymphoma
This is a study for children who have been previously treated for Leukemia/Lymphoma. In particular, it is a study for people who have a type of Leukemia/Lymphoma that involves B cells (a type of white cell), which contain the cancer. This is a new approach for treatment of Leukemia/Lymphoma that involves B cells (tumor cells). This study will take the subject's white blood cells (T cells) and modify them in order to target the cancer.
The subject's T cells will be modified in one or two different ways that will allow the cells to identify and kill the tumor cells (B cells). Both ways of modifying the cells tells the T cells to go to the B cells (tumor cells) and turn "on" and potentially kill the B cells (tumor cells). The modification is a genetic change to the T cells, or gene transfer, in order to allow the modified T cells to recognize your tumor cells but not other normal cells in the subject's body. These modified cells are called chimeric antigen receptor 19 (CART19) T-cells.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
At entry subjects will be staged and the suitability of their T cells for CART-19 manufacturing will be determined. Subjects who have adequate T cells will be leukapheresed to obtain large numbers of peripheral blood mononuclear cells (PBMC) for CART-19 manufacturing. The T cells will be purified from the PBMC, transduced with CART-19 lentiviral vector, expanded in vitro and then frozen for future administration. Chemotherapy will then be given. Following tumor burden reassessment, CART-19 cells will be thawed and infused.
Subjects will have blood tests to assess safety, and engraftment and persistence of the CART-19 cells at regular intervals through four weeks after their last infusion of the study. Following the 6 months of intensive follow-up, subjects will be evaluated quarterly for two years with a medical history, a physical examination, and blood tests. Following this evaluation, subjects will enter a roll-over study for annual follow-up by phone and questionnaire for an additional thirteen years to assess for the diagnosis of long-term health problems, such as development of new malignancy.
Primary objectives:
- Determine the safety and feasibility of administration of chimeric antigen receptor T cells transduced with the anti-CD 19 lentiviral vector (referred to as "CART-19" cells).
- Determine duration of in vivio survival of CART-19 cells. Real Time polymerase chain receptor (RT-PCR) analysis of whole blood will be used to detect and quantify survival of CART-19 TCR:4-1BB and TCR cells over time.
Secondary objectives:
- For patients with detectable disease, measure anti-tumor response due to CART-19 cell infusions.
- To determine if the 4-1BB transgene is superior to the TCR only transgene as measured by the relative engraftment levels of CART-19 TCR:4-1BB and TCR cells over time.
- For patients with stored or accessible tumor cells (such as patients with active chronic lymphocytic leukemia (CLL), acute lymphoblastic leukema (ALL), etc) determine tumor cell killing by CART-19 cells in vitro.
- Determine if cellular or humoral host immunity develops against the murine anti-CD19, and assess correlation with loss of detectable CART-19 (loss of engraftment).
- Determine the relative subsets of CART-19 T cells (Tcm, Tem, and Treg)
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19104
- CHOP - http://www.chop.edu/service/oncology/pediatric-cancer-research/cart-19-trial.html
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Male and female subjects with CD 19+ B cell malignancies in patients with no available curative treatment options (such as autologous or allogeneic SCT) who have limited prognosis (several months to <2 year survival) with currently available therapies will be enrolled:
Eligible diseases: CD 19+ leukemia or lymphoma
ALL without curative options for therapy, including those not eligible for allogeneic
SCT because of:
- age
- co-morbid disease
- other contraindications to TBI-based conditioning (required for ALL SCT)
- lack of suitable donor
- prior SCT
- Declines allo SCT (in CR3) as a therapeutic option after documented discussion about the role of SCT with a BMT physician not part of the study team. Note: Patient may be in any complete response, or patient may have active disease but responding or stable after most recent therapy. The intent is not to enroll patients with no degree of disease control, or rapidly increasing disease burden between enrollment and cell infusion.
Follicular lymphoma, previously identified as CD19+
- At least 2 prior combination chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy.
- Stage III-IV disease.
- Less than 1 year between last chemotherapy and progression (i.e. most recent progression free interval <1 year).
- Disease responding or stable after most recent therapy (chemotherapy, MoAb).
CLL
- At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy.
- Less than 1 year between last chemotherapy and progression (i.e. most recent progression free interval <1 year).
- Not eligible or appropriate for conventional allogeneic SCT
- Disease responding or stable after most recent therapy (chemotherapy, MoAb)
Mantle cell lymphoma
- Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT
- Disease responding or stable after most recent therapy (chemotherapy, MoAb)
- Relapsed after prior autologous SCT
- B-cell prolymphocytic leukemia (PLL) with relapsed or residual disease after at least 1 prior therapy and not eligible for allogeneic SCT.
Diffuse large cell lymphoma or other high-grade NHL, previously identified as CD19+
- Residual disease after primary therapy and not eligible for autologous SCT
- Relapsed after prior autologous SCT
- Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT
- Age 1 to 24 years. Patients ages 22-24 will only be enrolled if they are currently being treated at CHOP or another pediatric facility/oncologist
- Expected survival > 12 weeks
- Creatinine < 2.5 mg/dl and less than 2.5x normal for age
- ALT ≤ 5x normal
- Bilirubin <2.0 mg/dl
- Any relapse after prior SCT will make patient eligible regardless of other prior therapy
Patients with relapsed disease after prior allogeneic SCT (myeloablative or non-myeloablative) will be eligible if they meet all other inclusion criteria and
- Have no active GVHD and require no immunosuppression
- Are more than 4 months from transplant
- For those patients who require leukapheresis for T cell collection (i.e. no previously collected product exists), adequate venous access for apheresis or eligible for appropriate catheter placement, and no other contraindications for leukapheresis
- Voluntary informed consent is given
- Patients with CNS3 disease will be eligible if CNS disease is responsive to therapy (at infusion)
Exclusion Criteria:
- Pregnant or lactating women. The safety of this therapy on unborn children is not known. Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion
- Uncontrolled active infection
- Active hepatitis B or hepatitis C infection
- Concurrent use of systemic steroids at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of inhaled steroids, or hydrocortisone for physiological replacement in patients with adrenal insufficiency are permitted as well
- Presence of grade 2-4 acute or extensive chronic GVHD
- Under treatment for GVHD
- Previous treatment with any gene therapy products
- Any uncontrolled active medical disorder that would preclude participation as outlined.
- HIV infection.
- CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: CART-19 T Cells
The subject's thawed T cells will be modified in one or two different ways that will allow the cells to identify and kill the tumor cells (B cells).
The T cells will be infused over 10-15 minutes on days Days 0, and 1. Day 14 is tentative based on response.
|
Day 0: 10% of total dose Day 1: 30% of total dose if patient is stable (no significant toxicity) from prior dose.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Subjects With Study Related Adverse Events.
Time Frame: 24 weeks
|
Inclusive of any events that are "possibly", "likely", or "definitely" related to study treatment any time from the first day of study treatment until week 24.
|
24 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The Number of Subjects With a Successful Product Manufactured
Time Frame: 24 weeks
|
24 weeks
|
|
Number of Subjects With Complete Remission (CR).
Time Frame: 4 Weeks
|
Complete remission rate for subjects with Non-CNS3 ALL. National Comprehensive Cancer Network standard response criteria, which define complete remission (CR) as ,5% bone marrow blasts by morphologic determination, with no evidence of extramedullary disease or refractory disease. |
4 Weeks
|
Number of Subjects With Complete Remission With Incomplete Blood Count Recovery (CRi).
Time Frame: 4 Weeks
|
Complete remission rate for subjects with Non-CNS3 ALL. National Comprehensive Cancer Network standard response criteria, which define complete remission (CR) as ,5% bone marrow blasts by morphologic determination, with no evidence of extramedullary disease or refractory disease. |
4 Weeks
|
Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Gofshteyn JS, Shaw PA, Teachey DT, Grupp SA, Maude S, Banwell B, Chen F, Lacey SF, Melenhorst JJ, Edmonson MJ, Panzer J, Barrett DM, McGuire JL. Neurotoxicity after CTL019 in a pediatric and young adult cohort. Ann Neurol. 2018 Oct;84(4):537-546. doi: 10.1002/ana.25315. Epub 2018 Sep 26.
- Fitzgerald JC, Weiss SL, Maude SL, Barrett DM, Lacey SF, Melenhorst JJ, Shaw P, Berg RA, June CH, Porter DL, Frey NV, Grupp SA, Teachey DT. Cytokine Release Syndrome After Chimeric Antigen Receptor T Cell Therapy for Acute Lymphoblastic Leukemia. Crit Care Med. 2017 Feb;45(2):e124-e131. doi: 10.1097/CCM.0000000000002053.
- Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF, Mahnke YD, Melenhorst JJ, Rheingold SR, Shen A, Teachey DT, Levine BL, June CH, Porter DL, Grupp SA. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014 Oct 16;371(16):1507-17. doi: 10.1056/NEJMoa1407222. Erratum In: N Engl J Med. 2016 Mar 10;374(10):998.
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 10-007706, 815870
- CHP959 (OTHER: Children's Hospital of Philadelphia)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on B Cell Lymphoma
-
Iksuda Therapeutics Ltd.RecruitingFollicular Lymphoma | B-cell Lymphoma | Mantle Cell Lymphoma | Diffuse Large B Cell Lymphoma | B-cell Non-Hodgkin LymphomaAustralia, Canada, United States
-
Nathan DenlingerBristol-Myers SquibbRecruitingB-Cell Non-Hodgkin Lymphoma-Recurrent | Diffuse Large B-Cell Lymphoma-Recurrent | Follicular Lymphoma-Recurrent | High Grade B-Cell Lymphoma-Recurrent | Primary Mediastinal Large B-Cell Lymphoma-Recurrent | Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma-Recurrent and other conditionsUnited States
-
AstraZenecaRecruitingFollicular Lymphoma | Diffuse Large B Cell Lymphoma | High-grade B-cell Lymphoma | B-cell Non Hodgkin LymphomaKorea, Republic of, United States, Japan, Australia, Taiwan
-
Memorial Sloan Kettering Cancer CenterRecruitingLymphoma | Lymphoma, B-Cell | DLBCL - Diffuse Large B Cell Lymphoma | Large B-cell Lymphoma | Large-cell Lymphoma | Mediastinal B-Cell Diffuse Large Cell LymphomaUnited States
-
Massachusetts General HospitalVarian Medical SystemsRecruitingLymphoma, B-Cell | Follicular Lymphoma | Mantle Cell Lymphoma | Diffuse Large B Cell Lymphoma | Refractory Lymphoma | High-grade B-cell Lymphoma | Relapsed Cancer | Mediastinal Large B-cell LymphomaUnited States
-
University of ChicagoMerck Sharp & Dohme LLCRecruitingLymphoma | Lymphoma, B-Cell | B Cell Lymphoma | Diffuse Large B Cell Lymphoma | High-grade B-cell LymphomaUnited States
-
Curocell Inc.RecruitingHigh-grade B-cell Lymphoma | Diffuse Large B-cell Lymphoma (DLBCL) | Primary Mediastinal Large B-Cell Lymphoma (PMBCL) | Transformed Follicular Lymphoma (TFL) | Refractory Large B-cell Lymphoma | Relapsed Large B-cell LymphomaKorea, Republic of
-
Qian WenbinNot yet recruitingDiffuse Large B Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | Relapsed Diffuse Large B-Cell LymphomaChina
-
University of NebraskaBristol-Myers SquibbRecruitingFollicular Lymphoma | Refractory Non-Hodgkin Lymphoma | High-grade B-cell Lymphoma | DLBCL - Diffuse Large B Cell Lymphoma | Relapsed Non-Hodgkin Lymphoma | Mediastinal Large B-cell Lymphoma | Indolent B-Cell Non-Hodgkin LymphomaUnited States
-
Northwestern UniversityNational Cancer Institute (NCI)Active, not recruitingDiffuse Large B-Cell Lymphoma | Diffuse Large B-Cell Lymphoma, Not Otherwise Specified | High Grade B-Cell Lymphoma, Not Otherwise Specified | T-Cell/Histiocyte-Rich Large B-Cell Lymphoma | High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements | Diffuse Large B-Cell Lymphoma... and other conditionsUnited States
Clinical Trials on CART-19
-
Shanghai Unicar-Therapy Bio-medicine Technology...RecruitingAcute Myeloid LeukemiaChina
-
University of PennsylvaniaTerminatedLYMPHOCYTIC LEUKEMIA (CLL) OR SMALL LYMPHOCYTIC LYMPHOMA (SLL)United States
-
Fujian Medical UniversityUnknown
-
University of PennsylvaniaCompletedPatients With B Cell ALL, Relapsed or Refractory, With no Available Curative Treatment OptionsUnited States
-
University of PennsylvaniaCompletedRecurrent Adult Diffuse Large Cell Lymphoma | Recurrent Grade 1 Follicular Lymphoma | Recurrent Grade 2 Follicular Lymphoma | Recurrent Grade 3 Follicular Lymphoma | Recurrent Mantle Cell Lymphoma | Hematopoietic/Lymphoid Cancer | Adult Acute Lymphoblastic Leukemia in Remission | B-cell Chronic Lymphocytic... and other conditionsUnited States
-
University of PennsylvaniaTerminated
-
Beijing Sanwater Biological Technology Co., Ltd.UnknownAcute Lymphoblastic LeukemiaChina
-
University of Sao PauloHospital das Clínicas de Ribeirão Preto; Blood Center of Ribeirao PretoNot yet recruitingLymphoma, Non-Hodgkin | Leukemia, Acute LymphoblasticBrazil
-
University of PennsylvaniaCompletedAdult Patients Who Have Relapsed or Refractory CLL (3rd Line) or SLLUnited States
-
University of PennsylvaniaTerminatedLeukemia, Acute LymphoblasticUnited States