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Credit: Charles Haymond
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for JCAR015, a chimeric antigen receptor (CAR) T-cell therapy, to treat patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
Breakthrough designation is designed to help accelerate the development and review of new drugs for serious or life-threatening conditions.
The designation comes with potential benefits, including intensive FDA guidance and eligibility for priority review. It is granted to applicants when preliminary clinical evidence indicates the drug may demonstrate substantial improvement over existing therapies on one or more clinical endpoints.
The FDA recently granted JCAR015 orphan designation to treat ALL as well.
JCAR015 consists of autologous T cells expressing a CD19-specific, CD28/CD3z CAR. The treatment has shown promise in an ongoing phase 1 trial of patients with B-cell ALL.
Initial results from this study were published in Science Translational Medicine last year and in February. Updated results were presented at the AACR Annual Meeting in April.
At that point, the researchers had enrolled 22 adult patients with relapsed or refractory B-ALL who were minimal residual disease-positive or were in first complete remission at enrollment. Patients in complete remission were monitored and only received JCAR015 if they relapsed.
The remaining patients received re-induction chemotherapy (physician’s choice), followed by an infusion of JCAR015. After treatment, patients could receive allogeneic transplant, a different salvage therapy, or monitoring.
Eighty-two percent of patients achieved a complete response to JCAR015. The average time to complete response was about 24.5 days.
Twelve of the responders were eligible for transplant. Of the 8 patients who ultimately underwent transplant and survived, 1 relapsed, but the rest remained in remission.
Ten patients had died at the time of the AACR presentation. Six deaths were a result of disease relapse or progression, and 2 patients died of complications from stem cell transplant.
The 2 remaining deaths prompted a temporary suspension of enrollment in this trial. Those deaths were related to complications from cytokine release syndrome. One patient died of cardiovascular disease, and the other died following persistent seizure activity.
So researchers at the Memorial Sloan-Kettering Cancer Center, where the trial is being conducted, reviewed these cases. The results prompted them to amend trial enrollment criteria and dosing recommendations. Now, patients with cardiac disease are ineligible to receive JCAR015.
And the T-cell dose a patient receives will depend on the extent of his or her disease. The hope is that this will reduce the risk of cytokine release syndrome and any resulting seizures. The researchers also noted that the monoclonal antibody tocilizumab has proven effective in treating cytokine release syndrome.
In addition to this trial, JCAR015 is under investigation at Memorial Sloan-Kettering Cancer Center in a phase 1 trial of patients with relapsed and refractory non-Hodgkin lymphoma.
Two other CAR T-cell product candidates under development by the same company, Juno Therapeutics, Inc., are being tested in clinical trials as well. JCAR017 is under investigation at Seattle Children’s Hospital for relapsed/refractory CD19-positive pediatric leukemia.
JCAR014 is being tested for refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, and ALL at the Fred Hutchinson Cancer Research Center. Data on these programs are set to be presented at the 56th ASH Annual Meeting next week in San Francisco. 
Credit: Charles Haymond
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for JCAR015, a chimeric antigen receptor (CAR) T-cell therapy, to treat patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
Breakthrough designation is designed to help accelerate the development and review of new drugs for serious or life-threatening conditions.
The designation comes with potential benefits, including intensive FDA guidance and eligibility for priority review. It is granted to applicants when preliminary clinical evidence indicates the drug may demonstrate substantial improvement over existing therapies on one or more clinical endpoints.
The FDA recently granted JCAR015 orphan designation to treat ALL as well.
JCAR015 consists of autologous T cells expressing a CD19-specific, CD28/CD3z CAR. The treatment has shown promise in an ongoing phase 1 trial of patients with B-cell ALL.
Initial results from this study were published in Science Translational Medicine last year and in February. Updated results were presented at the AACR Annual Meeting in April.
At that point, the researchers had enrolled 22 adult patients with relapsed or refractory B-ALL who were minimal residual disease-positive or were in first complete remission at enrollment. Patients in complete remission were monitored and only received JCAR015 if they relapsed.
The remaining patients received re-induction chemotherapy (physician’s choice), followed by an infusion of JCAR015. After treatment, patients could receive allogeneic transplant, a different salvage therapy, or monitoring.
Eighty-two percent of patients achieved a complete response to JCAR015. The average time to complete response was about 24.5 days.
Twelve of the responders were eligible for transplant. Of the 8 patients who ultimately underwent transplant and survived, 1 relapsed, but the rest remained in remission.
Ten patients had died at the time of the AACR presentation. Six deaths were a result of disease relapse or progression, and 2 patients died of complications from stem cell transplant.
The 2 remaining deaths prompted a temporary suspension of enrollment in this trial. Those deaths were related to complications from cytokine release syndrome. One patient died of cardiovascular disease, and the other died following persistent seizure activity.
So researchers at the Memorial Sloan-Kettering Cancer Center, where the trial is being conducted, reviewed these cases. The results prompted them to amend trial enrollment criteria and dosing recommendations. Now, patients with cardiac disease are ineligible to receive JCAR015.
And the T-cell dose a patient receives will depend on the extent of his or her disease. The hope is that this will reduce the risk of cytokine release syndrome and any resulting seizures. The researchers also noted that the monoclonal antibody tocilizumab has proven effective in treating cytokine release syndrome.
In addition to this trial, JCAR015 is under investigation at Memorial Sloan-Kettering Cancer Center in a phase 1 trial of patients with relapsed and refractory non-Hodgkin lymphoma.
Two other CAR T-cell product candidates under development by the same company, Juno Therapeutics, Inc., are being tested in clinical trials as well. JCAR017 is under investigation at Seattle Children’s Hospital for relapsed/refractory CD19-positive pediatric leukemia.
JCAR014 is being tested for refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, and ALL at the Fred Hutchinson Cancer Research Center. Data on these programs are set to be presented at the 56th ASH Annual Meeting next week in San Francisco.
Credit: Charles Haymond
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for JCAR015, a chimeric antigen receptor (CAR) T-cell therapy, to treat patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
Breakthrough designation is designed to help accelerate the development and review of new drugs for serious or life-threatening conditions.
The designation comes with potential benefits, including intensive FDA guidance and eligibility for priority review. It is granted to applicants when preliminary clinical evidence indicates the drug may demonstrate substantial improvement over existing therapies on one or more clinical endpoints.
The FDA recently granted JCAR015 orphan designation to treat ALL as well.
JCAR015 consists of autologous T cells expressing a CD19-specific, CD28/CD3z CAR. The treatment has shown promise in an ongoing phase 1 trial of patients with B-cell ALL.
Initial results from this study were published in Science Translational Medicine last year and in February. Updated results were presented at the AACR Annual Meeting in April.
At that point, the researchers had enrolled 22 adult patients with relapsed or refractory B-ALL who were minimal residual disease-positive or were in first complete remission at enrollment. Patients in complete remission were monitored and only received JCAR015 if they relapsed.
The remaining patients received re-induction chemotherapy (physician’s choice), followed by an infusion of JCAR015. After treatment, patients could receive allogeneic transplant, a different salvage therapy, or monitoring.
Eighty-two percent of patients achieved a complete response to JCAR015. The average time to complete response was about 24.5 days.
Twelve of the responders were eligible for transplant. Of the 8 patients who ultimately underwent transplant and survived, 1 relapsed, but the rest remained in remission.
Ten patients had died at the time of the AACR presentation. Six deaths were a result of disease relapse or progression, and 2 patients died of complications from stem cell transplant.
The 2 remaining deaths prompted a temporary suspension of enrollment in this trial. Those deaths were related to complications from cytokine release syndrome. One patient died of cardiovascular disease, and the other died following persistent seizure activity.
So researchers at the Memorial Sloan-Kettering Cancer Center, where the trial is being conducted, reviewed these cases. The results prompted them to amend trial enrollment criteria and dosing recommendations. Now, patients with cardiac disease are ineligible to receive JCAR015.
And the T-cell dose a patient receives will depend on the extent of his or her disease. The hope is that this will reduce the risk of cytokine release syndrome and any resulting seizures. The researchers also noted that the monoclonal antibody tocilizumab has proven effective in treating cytokine release syndrome.
In addition to this trial, JCAR015 is under investigation at Memorial Sloan-Kettering Cancer Center in a phase 1 trial of patients with relapsed and refractory non-Hodgkin lymphoma.
Two other CAR T-cell product candidates under development by the same company, Juno Therapeutics, Inc., are being tested in clinical trials as well. JCAR017 is under investigation at Seattle Children’s Hospital for relapsed/refractory CD19-positive pediatric leukemia.
JCAR014 is being tested for refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, and ALL at the Fred Hutchinson Cancer Research Center. Data on these programs are set to be presented at the 56th ASH Annual Meeting next week in San Francisco.