Trial Outcomes & Findings for Therapy to Treat Ewing's Sarcoma, Rhabdomyosarcoma or Neuroblastoma (NCT NCT00923351)

Last Updated: 2018-06-15

Results Overview

A positive response to the tumor vaccine requires a positive reaction in at least one of the two assays below (immune responses to tumor lysates using ex vivo and delayed type of hypersensitivity (DTH). The presence of a positive delayed type of hypersensitivity (DTH) reaction to the tumor lysate in a patient who did not show a positive DTH reaction prior to immunotherapy. A positive reaction is induration of at least 0.5 cm. Immunotherapy administered to patients with recurrent or metastatic pediatric solid tumors such as Ewing's sarcoma, rhabdomyosarcoma, or neuroblastoma. Each vaccine is given as 6 separate injections. Three intradermal on one arm or leg and three subcutaneous on the other arm or leg.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

44 participants

Primary outcome timeframe

Week 8, 14, 20 (Arm A) and on Days 42, 84 and 126 (± 7 days) (Arm B)

Results posted on

2018-06-15

Participant Flow

Forty-four patients were enrolled. Twelve patients were not treated in Arm A or B because they did not get far enough in the study to be designated for an Arm.

Participant milestones

Participant milestones
Measure	Arm A - Participants Who Did Not Receive rhIL-7 Six patients with Ewings sarcoma family or tumors (ESFT) participants will receive cytotoxic/lympholytic therapy with cyclophosphamide and fludarabine (if cluster of differentiation 4 (CD4) count \> 200 cells/mcl). Participant will receive Tumor lysate/keyhole limpet hemocyanin (KLH) pulsed dendritic cell vaccine followed by Infusion of 8H9/CD25 depleted autologous lymphocyte infusion on Day 1, followed by Tumor lysate/KLH pulsed dendritic cell vaccine on week 4, 6, 8, 10, and 12.	Arm B - Participants Who Received rhIL-7 Eight patients with rhabdomyosarcoma, fifteen patients with Ewings sarcoma family or tumors (ESFT), two patients with desmoplastic small round cell tumor, and one patient with synovial cell sarcoma participants will receive CYT107 20 mcg/kg/dose subcutaneous (SQ) (approx. 48h prior to vaccine\[Day 0\]), Tumor lysate/KLH pulsed dendritic cell vaccine followed by Infuse 8H9/CD25 depleted autologous lymphocyte infusion on Day 2, followed by CYT107 20 mcg/kg/dose SQ on days 14, 28 and 42 (± 7 days), and Tumor lysate/KLH pulsed dendritic cell vaccine on Days 16, 30, 44, 56, and 70 (± 7 days). Apheresis/flow cytometry/delayed type of hypersensitivity (DTH) responses for immune endpoint monitoring (skin tests) will be performed on Week 8, 14, 20 (Arm A) and on Days 42, 84 and 126 (+/- 7 days) (Arm B); and radiographic studies for clinical restaging will be performed on Week 8 and 20 (Arm A) and Days 42 and 126 (+/- 7 days) (Arm B).	Enrolled But Not Assigned to Treatment Twelve participants were not treated in Arm A or Arm B because they did not get far enough in the study to be designated for an Arm. Were unable to obtain apheresis, and adequate tumor samples.
Overall Study STARTED	6	26	12
Overall Study COMPLETED	6	26	0
Overall Study NOT COMPLETED	0	0	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A - Participants Who Did Not Receive rhIL-7 Six patients with Ewings sarcoma family or tumors (ESFT) participants will receive cytotoxic/lympholytic therapy with cyclophosphamide and fludarabine (if cluster of differentiation 4 (CD4) count \> 200 cells/mcl). Participant will receive Tumor lysate/keyhole limpet hemocyanin (KLH) pulsed dendritic cell vaccine followed by Infusion of 8H9/CD25 depleted autologous lymphocyte infusion on Day 1, followed by Tumor lysate/KLH pulsed dendritic cell vaccine on week 4, 6, 8, 10, and 12.	Arm B - Participants Who Received rhIL-7 Eight patients with rhabdomyosarcoma, fifteen patients with Ewings sarcoma family or tumors (ESFT), two patients with desmoplastic small round cell tumor, and one patient with synovial cell sarcoma participants will receive CYT107 20 mcg/kg/dose subcutaneous (SQ) (approx. 48h prior to vaccine\[Day 0\]), Tumor lysate/KLH pulsed dendritic cell vaccine followed by Infuse 8H9/CD25 depleted autologous lymphocyte infusion on Day 2, followed by CYT107 20 mcg/kg/dose SQ on days 14, 28 and 42 (± 7 days), and Tumor lysate/KLH pulsed dendritic cell vaccine on Days 16, 30, 44, 56, and 70 (± 7 days). Apheresis/flow cytometry/delayed type of hypersensitivity (DTH) responses for immune endpoint monitoring (skin tests) will be performed on Week 8, 14, 20 (Arm A) and on Days 42, 84 and 126 (+/- 7 days) (Arm B); and radiographic studies for clinical restaging will be performed on Week 8 and 20 (Arm A) and Days 42 and 126 (+/- 7 days) (Arm B).	Enrolled But Not Assigned to Treatment Twelve participants were not treated in Arm A or Arm B because they did not get far enough in the study to be designated for an Arm. Were unable to obtain apheresis, and adequate tumor samples.
Overall Study no apheresis/adequate tumor sample	0	0	12

Baseline Characteristics

Therapy to Treat Ewing's Sarcoma, Rhabdomyosarcoma or Neuroblastoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A - Participants Who Did Not Receive rhIL-7 n=6 Participants Six patients with Ewings sarcoma family or tumors (ESFT) participants will receive cytotoxic/lympholytic therapy with cyclophosphamide and fludarabine (if cluster of differentiation 4 (CD4) count \> 200 cells/mcl). Participants will receive Tumor lysate/KLH pulsed dendritic cell vaccine followed by Infusion of 8H9/CD25 depleted autologous lymphocyte infusion on Day 1, followed by Tumor lysate/KLH pulsed dendritic cell vaccine on week 4, 6, 8, 10, and 12.	Arm B - Participants Who Received rhIL-7 n=26 Participants Eight patients with rhabdomyosarcoma, fifteen patients with Ewings sarcoma family or tumors (ESFT), two patients with desmoplastic small round cell tumor, and one patient with synovial cell sarcoma participants will receive CYT107 20 mcg/kg/dose SQ (approx. 48h prior to vaccine\[Day 0\]), Tumor lysate/KLH pulsed dendritic cell vaccine followed by Infuse 8H9/CD25 depleted autologous lymphocyte infusion on Day 2, followed by CYT107 20 mcg/kg/dose SQ on days 14, 28 and 42 (± 7 days), and Tumor lysate/KLH pulsed dendritic cell vaccine on Days 16, 30, 44, 56, and 70 (± 7 days). Apheresis/flow cytometry/delayed type of hypersensitivity (DTH) responses for immune endpoint monitoring (skin tests) will be performed on Week 8, 14, 20 (Arm A) and on Days 42, 84 and 126 (+/- 7 days) (Arm B); and radiographic studies for clinical restaging will be performed on Week 8 and 20 (Arm A) and Days 42 and 126 (+/- 7 days) (Arm B).	Total n=32 Participants Total of all reporting groups
Age, Categorical <=18 years	4 Participants n=5 Participants	15 Participants n=7 Participants	19 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	11 Participants n=7 Participants	13 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	21.6 years STANDARD_DEVIATION 7.56 • n=5 Participants	20.96 years STANDARD_DEVIATION 8.19 • n=7 Participants	21.0 years STANDARD_DEVIATION 8.04 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	20 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	20 Participants n=7 Participants	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White (non-Hispanic)	6 Participants n=5 Participants	20 Participants n=7 Participants	26 Participants n=5 Participants
Race/Ethnicity, Customized More than one race	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	6 Participants n=5 Participants	26 Participants n=7 Participants	32 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 8, 14, 20 (Arm A) and on Days 42, 84 and 126 (± 7 days) (Arm B)

Population: Five of the original six participants from Arm A were analyzed because one subject was changed to a special exemption.

Outcome measures

Outcome measures
Measure	Arm A - Participants Who Did Not Receive rhIL-7 n=5 Participants Six patients with Ewings sarcoma family or tumors (ESFT) participants will receive cytotoxic/lympholytic therapy with cyclophosphamide and fludarabine (if cluster of differentiation 4 (CD4) count \> 200 cells/mcl). Participants will receive Tumor lysate/KLH pulsed dendritic cell vaccine followed by Infusion of 8H9/CD25 depleted autologous lymphocyte infusion on Day 1, followed by Tumor lysate/KLH pulsed dendritic cell vaccine on week 4, 6, 8, 10, and 12.	Arm B - Participants Who Received rhIL-7 n=26 Participants Eight patients with rhabdomyosarcoma, fifteen patients with Ewings sarcoma family or tumors (ESFT), two patients with desmoplastic small round cell tumor, and one patient with synovial cell sarcoma participants will receive CYT107 20 mcg/kg/dose SQ (approx. 48h prior to vaccine\[Day 0\]), Tumor lysate/KLH pulsed dendritic cell vaccine followed by Infuse 8H9/CD25 depleted autologous lymphocyte infusion on Day 2, followed by CYT107 20 mcg/kg/dose SQ on days 14, 28 and 42 (± 7 days), and Tumor lysate/KLH pulsed dendritic cell vaccine on Days 16, 30, 44, 56, and 70 (± 7 days). Apheresis/flow cytometry/delayed type of hypersensitivity (DTH) responses for immune endpoint monitoring (skin tests) will be performed on Week 8, 14, 20 (Arm A) and on Days 42, 84 and 126 (+/- 7 days) (Arm B); and radiographic studies for clinical restaging will be performed on Week 8 and 20 (Arm A) and Days 42 and 126 (+/- 7 days) (Arm B).
Number of Participants With a Positive Immune Response as Evidenced by the Delayed Type of Hypersensitivity (DTH) Reaction Assay	0 Participants	15 Participants

PRIMARY outcome

Timeframe: Date treatment consent signed to date off study, approximately 49.5 months

Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

Outcome measures

Outcome measures
Measure	Arm A - Participants Who Did Not Receive rhIL-7 n=6 Participants Six patients with Ewings sarcoma family or tumors (ESFT) participants will receive cytotoxic/lympholytic therapy with cyclophosphamide and fludarabine (if cluster of differentiation 4 (CD4) count \> 200 cells/mcl). Participants will receive Tumor lysate/KLH pulsed dendritic cell vaccine followed by Infusion of 8H9/CD25 depleted autologous lymphocyte infusion on Day 1, followed by Tumor lysate/KLH pulsed dendritic cell vaccine on week 4, 6, 8, 10, and 12.	Arm B - Participants Who Received rhIL-7 n=26 Participants Eight patients with rhabdomyosarcoma, fifteen patients with Ewings sarcoma family or tumors (ESFT), two patients with desmoplastic small round cell tumor, and one patient with synovial cell sarcoma participants will receive CYT107 20 mcg/kg/dose SQ (approx. 48h prior to vaccine\[Day 0\]), Tumor lysate/KLH pulsed dendritic cell vaccine followed by Infuse 8H9/CD25 depleted autologous lymphocyte infusion on Day 2, followed by CYT107 20 mcg/kg/dose SQ on days 14, 28 and 42 (± 7 days), and Tumor lysate/KLH pulsed dendritic cell vaccine on Days 16, 30, 44, 56, and 70 (± 7 days). Apheresis/flow cytometry/delayed type of hypersensitivity (DTH) responses for immune endpoint monitoring (skin tests) will be performed on Week 8, 14, 20 (Arm A) and on Days 42, 84 and 126 (+/- 7 days) (Arm B); and radiographic studies for clinical restaging will be performed on Week 8 and 20 (Arm A) and Days 42 and 126 (+/- 7 days) (Arm B).
Toxicity	6 Participants	24 Participants

PRIMARY outcome

Timeframe: Time between the first day of treatment to the day of death or at the conclusion of 5 years of follow-up, whichever comes first, assessed up to approximately 11 years.

Overall survival is defined as the time between the first day of treatment to the day of death.

Outcome measures

Outcome measures
Measure	Arm A - Participants Who Did Not Receive rhIL-7 n=6 Participants Six patients with Ewings sarcoma family or tumors (ESFT) participants will receive cytotoxic/lympholytic therapy with cyclophosphamide and fludarabine (if cluster of differentiation 4 (CD4) count \> 200 cells/mcl). Participants will receive Tumor lysate/KLH pulsed dendritic cell vaccine followed by Infusion of 8H9/CD25 depleted autologous lymphocyte infusion on Day 1, followed by Tumor lysate/KLH pulsed dendritic cell vaccine on week 4, 6, 8, 10, and 12.	Arm B - Participants Who Received rhIL-7 n=26 Participants Eight patients with rhabdomyosarcoma, fifteen patients with Ewings sarcoma family or tumors (ESFT), two patients with desmoplastic small round cell tumor, and one patient with synovial cell sarcoma participants will receive CYT107 20 mcg/kg/dose SQ (approx. 48h prior to vaccine\[Day 0\]), Tumor lysate/KLH pulsed dendritic cell vaccine followed by Infuse 8H9/CD25 depleted autologous lymphocyte infusion on Day 2, followed by CYT107 20 mcg/kg/dose SQ on days 14, 28 and 42 (± 7 days), and Tumor lysate/KLH pulsed dendritic cell vaccine on Days 16, 30, 44, 56, and 70 (± 7 days). Apheresis/flow cytometry/delayed type of hypersensitivity (DTH) responses for immune endpoint monitoring (skin tests) will be performed on Week 8, 14, 20 (Arm A) and on Days 42, 84 and 126 (+/- 7 days) (Arm B); and radiographic studies for clinical restaging will be performed on Week 8 and 20 (Arm A) and Days 42 and 126 (+/- 7 days) (Arm B).
Overall Survival	2.4 years Interval 1.0 to 3.3	4.3 years Interval 0.9 to 10.4

Adverse Events

Arm A - Participants Who Did Not Receive rhIL-7

Serious events: 6 serious events

Other events: 6 other events

Deaths: 0 deaths

Arm B - Participants Who Received rhIL-7

Serious events: 12 serious events

Other events: 24 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Arm A - Participants Who Did Not Receive rhIL-7 n=6 participants at risk Six patients with Ewings sarcoma family or tumors (ESFT) participants will receive cytotoxic/lympholytic therapy with cyclophosphamide and fludarabine (if cluster of differentiation 4 (CD4) count \> 200 cells/mcl). Participants will receive Tumor lysate/KLH pulsed dendritic cell vaccine followed by Infusion of 8H9/CD25 depleted autologous lymphocyte infusion on Day 1, followed by Tumor lysate/KLH pulsed dendritic cell vaccine on week 4, 6, 8, 10, and 12.	Arm B - Participants Who Received rhIL-7 n=26 participants at risk Eight patients with rhabdomyosarcoma, fifteen patients with Ewings sarcoma family or tumors (ESFT), two patients with desmoplastic small round cell tumor, and one patient with synovial cell sarcoma participants will receive CYT107 20 mcg/kg/dose SQ (approx. 48h prior to vaccine\[Day 0\]), Tumor lysate/KLH pulsed dendritic cell vaccine followed by Infuse 8H9/CD25 depleted autologous lymphocyte infusion on Day 2, followed by CYT107 20 mcg/kg/dose SQ on days 14, 28 and 42 (± 7 days), and Tumor lysate/KLH pulsed dendritic cell vaccine on Days 16, 30, 44, 56, and 70 (± 7 days). Apheresis/flow cytometry/delayed type of hypersensitivity (DTH) responses for immune endpoint monitoring (skin tests) will be performed on Week 8, 14, 20 (Arm A) and on Days 42, 84 and 126 (+/- 7 days) (Arm B); and radiographic studies for clinical restaging will be performed on Week 8 and 20 (Arm A) and Days 42 and 126 (+/- 7 days) (Arm B).
General disorders Death not associated with CTCAE term: Disease progression NOS	0.00% 0/6 • Date treatment consent signed to date off study, approximately 49.5 months.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 49.5 months.
Nervous system disorders Dizziness	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 49.5 months.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 49.5 months.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	0.00% 0/6 • Date treatment consent signed to date off study, approximately 49.5 months.	7.7% 2/26 • Number of events 2 • Date treatment consent signed to date off study, approximately 49.5 months.
General disorders Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	50.0% 3/6 • Number of events 3 • Date treatment consent signed to date off study, approximately 49.5 months.	19.2% 5/26 • Number of events 5 • Date treatment consent signed to date off study, approximately 49.5 months.
Cardiac disorders Hypertension	0.00% 0/6 • Date treatment consent signed to date off study, approximately 49.5 months.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 49.5 months.
Infections and infestations Infection with unknown ANC: Upper airway NOS	0.00% 0/6 • Date treatment consent signed to date off study, approximately 49.5 months.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 49.5 months.
Nervous system disorders Mood alteration: depression	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 49.5 months.	0.00% 0/26 • Date treatment consent signed to date off study, approximately 49.5 months.
Respiratory, thoracic and mediastinal disorders Pain: Chest/thorax NOS	0.00% 0/6 • Date treatment consent signed to date off study, approximately 49.5 months.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 49.5 months.
Musculoskeletal and connective tissue disorders Pain::Extremity-limb	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 49.5 months.	11.5% 3/26 • Number of events 3 • Date treatment consent signed to date off study, approximately 49.5 months.
Respiratory, thoracic and mediastinal disorders Pleural effusion (non-malignant)	0.00% 0/6 • Date treatment consent signed to date off study, approximately 49.5 months.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 49.5 months.
Renal and urinary disorders Urine color change	0.00% 0/6 • Date treatment consent signed to date off study, approximately 49.5 months.	3.8% 1/26 • Number of events 1 • Date treatment consent signed to date off study, approximately 49.5 months.

Other adverse events

Additional Information

Dr. John Glod

National Cancer Institute, National Institutes of Health

Phone: 301-451-0391

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place