Clinical Trials /

Study of CAR T-Cells Targeting the GD2 With IL-15+iCaspase9 for Relapsed/Refractory Neuroblastoma

NCT03721068

Description:

The body has different ways of fighting infections 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 molecules that fight infections and protect your body from diseases caused by bacteria and toxic substances. Antibodies work by sticking to those bacteria or substances, which stops them from growing and causing bad effects. T cells 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 enough to cure most patients. This study is designed to combine both T cells and antibodies in order to create a more effective treatment. The treatment that is being researched is called autologous T lymphocyte chimeric antigen receptor cells (CAR) cells targeted against the disialoganglioside (GD2) antigen that express Interleukin (IL)-15, and the inducible caspase 9 safety switch (iC9), also known as iC9.GD2.CAR.IL-15 T cells. In previous studies, it has been shown that when T cells have part of an antibody attached to them they are better at recognizing and killing cancer cells. The antibody that will be used in this study is called anti-GD2. This antibody floats around in the blood and can detect and stick to cancer cells called neuroblastoma cells because they have a substance on the outside of the cells called GD2. For this study, the anti-GD2 antibody has been changed so instead of floating freely in the blood, it is now joined to the T cells. However, it is unknown how long the iC9.GD2.CAR.IL-15 T cells last in the body, so their chances of fighting cancer cells are not well known. To improve the tumor fighting power of GD2-CAR-T cells, our researchers have added two additional components to these cells. The IL-15 gene was added so that the GD2-CAR-T cells can attack tumor cells more effectively. Interleukin-15 (IL-15) is a chemical that cells use to communicate with one another. Other research using IL-15 in combination with CAR-T cells has shown there is an increase in the body's ability to allow the CAR-T cells to survive and grow in the body. The iC9 gene was added as an "off switch" so it can stop the activity of the GD2-CAR-T cells if you experience any serious bad side effects. Bad side effects seen previously in patients receiving the GD2 antibody alone include pain. In this study, the "stop switch" can be used to turn off the GD2-CAR-T cells if you experience intense pain that does not respond to normal pain treatments. The primary purpose of this study is to determine whether receiving iC9.GD2.IL-15 T cells is safe and tolerable in patients with relapsed/refractory neuroblastoma.

Related Conditions:
  • Ganglioneuroblastoma
  • Neuroblastoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of CAR T-Cells Targeting the GD2 With IL-15+iCaspase9 for Relapsed/Refractory Neuroblastoma
  • Official Title: Phase I Study of Autologous Activated T-cells Transduced With a 3rd Generation GD2 Chimeric Antigen Receptor, Co-expression of IL-15, and iCaspase9 Safety Switch Administered To Patients With Relapsed or Refractory Neuroblastoma

Clinical Trial IDs

  • ORG STUDY ID: LCCC 1743-ATL
  • NCT ID: NCT03721068

Conditions

  • Neuroblastoma

Interventions

DrugSynonymsArms
iC9.GD2.CAR.IL-15 T-cellsiC9.GD2.CAR.IL-15 T-cells
CyclophosphamideiC9.GD2.CAR.IL-15 T-cells
FludarabineiC9.GD2.CAR.IL-15 T-cells

Purpose

The body has different ways of fighting infections 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 molecules that fight infections and protect your body from diseases caused by bacteria and toxic substances. Antibodies work by sticking to those bacteria or substances, which stops them from growing and causing bad effects. T cells 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 enough to cure most patients. This study is designed to combine both T cells and antibodies in order to create a more effective treatment. The treatment that is being researched is called autologous T lymphocyte chimeric antigen receptor cells (CAR) cells targeted against the disialoganglioside (GD2) antigen that express Interleukin (IL)-15, and the inducible caspase 9 safety switch (iC9), also known as iC9.GD2.CAR.IL-15 T cells. In previous studies, it has been shown that when T cells have part of an antibody attached to them they are better at recognizing and killing cancer cells. The antibody that will be used in this study is called anti-GD2. This antibody floats around in the blood and can detect and stick to cancer cells called neuroblastoma cells because they have a substance on the outside of the cells called GD2. For this study, the anti-GD2 antibody has been changed so instead of floating freely in the blood, it is now joined to the T cells. However, it is unknown how long the iC9.GD2.CAR.IL-15 T cells last in the body, so their chances of fighting cancer cells are not well known. To improve the tumor fighting power of GD2-CAR-T cells, our researchers have added two additional components to these cells. The IL-15 gene was added so that the GD2-CAR-T cells can attack tumor cells more effectively. Interleukin-15 (IL-15) is a chemical that cells use to communicate with one another. Other research using IL-15 in combination with CAR-T cells has shown there is an increase in the body's ability to allow the CAR-T cells to survive and grow in the body. The iC9 gene was added as an "off switch" so it can stop the activity of the GD2-CAR-T cells if you experience any serious bad side effects. Bad side effects seen previously in patients receiving the GD2 antibody alone include pain. In this study, the "stop switch" can be used to turn off the GD2-CAR-T cells if you experience intense pain that does not respond to normal pain treatments. The primary purpose of this study is to determine whether receiving iC9.GD2.IL-15 T cells is safe and tolerable in patients with relapsed/refractory neuroblastoma.

Detailed Description

      We plan to conduct a single center, open-label, Phase I clinical trial to establish a safe
      dose (i.e., number of cells/kg) of autologous iC9.GD2.CAR.IL-15 T-cells in pediatric patients
      with relapsed or refractory neuroblastoma. The study will enroll a minimum of 10 subjects;
      all subjects will undergo lymphodepleting chemotherapy prior to the cell infusion as outlined
      in section 4.2.2. The continual reassessment method (CRM) will be used to estimate the
      maximum-tolerated dose (MTD) of cells that can be administered in dose escalation cohorts
      comprised of 2-6 subjects. The final MTD will be the dose with estimated probability of DLT
      closest to the target toxicity rate of 20%. The three cell doses that will be evaluated are
      outlined in the table below starting at the lowest dose level 1: 0.5 x 106 CAR+ cells/kg
      iC9.GD2.CAR.IL-15 T cells. Cohort enrollment will be staggered and each subject must complete
      at least 2 weeks of cell treatment without incident of DLT before another subject can be
      enrolled at that dose level. A minimum of two subjects must complete the 4-week post-infusion
      DLT safety assessment period before cohort enrollment of subjects at the next higher dose
      level will be considered. If dose level 1 is determined to be above a tolerable dose,
      de-escalation would occur to dose level -1 where subjects would receive 0.25 x 106 CAR+
      cells/kg. After dose escalation is completed, an expansion cohort will enroll up to 8
      subjects at the maximum tolerated dose (MTD) to further assess the safety and efficacy of
      iC9.GD2.CAR.IL-15 T-cells. In the expansion phase, subjects will receive iC9.GD2.CAR.IL-15
      T-cells at the maximum tolerated dose (MTD) with lymphodepletion given prior to a cell
      product administration.

      Cell Procurement

      Up to 3 mL/kg of peripheral blood will be obtained (in up to 3 collections) from patients for
      cell procurement. For subjects with inadequate lymphocyte count or who are unable to donate
      adequate amounts of peripheral blood, a leukopheresis may be performed to isolate sufficient
      T cells. The parameters for pheresis will be up to 2 blood volumes. Approximately 4-6 weeks
      later, subjects for whom cells have been successfully generated and who meet eligibility
      criteria for lymphodepletion will undergo lymphodepleting chemotherapy.

      Lymphodepleting Regimen

      All subjects will be given lymphodepleting chemotherapy with cyclophosphamide and
      fludarabine. This will consist of four days total and should be timed to be completed 2-14
      days before planned infusion of CAR T-cells.

      Cyclophosphamide will be given IV 500 mg/m2/day on days 1-2 and fludarabine will be given IV
      30 mg/m2/day on days 1-4. No mesna will be required, although it may be used at investigator
      discretion.

      Administration of iC9.GD2.CAR.IL-15 T cells

      Post lymphodepletion, subjects who meet eligibility criteria for cellular therapy will
      receive iC9.GD2.CAR.IL-15 T cells within 2-14 days after completing the lymphodepleting
      chemotherapy regimen. We will administer T-cells post lymphodepletion as dosed above.

      After dose escalation is completed, an expansion cohort will enroll up to 8 subjects to
      further assess the safety and efficacy of iC9.GD2.CAR.IL-15 T-cells. In the expansion phase,
      patients who meet criteria outlined in Section 4.2.5 will be allowed to receive a second cell
      infusion.

      Duration of Therapy

      Therapy in LCCC 1743-ATL involves infusion of iC9.GD2.CAR.IL-15 CAR T cells. Treatment 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.

        -  Subject is ineligible for a second infusion

      Duration of Follow-up

      Subjects will be followed for up to 15 years for RCR evaluation or until death, whichever
      occurs first. In addition to this follow-up, subjects removed from study treatment for
      unacceptable adverse events will be followed until resolution or stabilization of the adverse
      event.

      Subjects who receive new therapy after receiving a cell infusion will still be required to
      complete abbreviated follow up procedures.
    

Trial Arms

NameTypeDescriptionInterventions
iC9.GD2.CAR.IL-15 T-cellsExperimentalThe continuous reassessment method (CRM) will be used to estimate the maximum-tolerated dose (MTD) of cells that to be given in dose escalation cohorts comprised of 2-6 subjects. The final MTD will be the dose with estimated probability of dose limiting toxicity (DLT) closest to the target toxicity rate of 20%. Three cell doses will be evaluated: 0.5 x 10^6 cells/kg, 1.0 x 10^6 cells/kg, 1.5 x 10^6 cells/kg. Cohort enrollment will be staggered and each subject must complete at least 2 weeks of the cell treatment without incident of DLT before another subject can be enrolled at that dose level. A minimum of two subjects must complete the 4-week post-infusion DLT period before enrollment at the next higher dose level will be considered. If dose level 1 is determined to be above a tolerable dose, de-escalation would occur to dose level -1 where subjects would receive 0.25 x 10^6 cells/kg.
  • iC9.GD2.CAR.IL-15 T-cells
  • Cyclophosphamide
  • Fludarabine

Eligibility Criteria

        Inclusion Criteria:

          1. Age greater than 18 months and less than 18 years at the time of consent.

          2. Adequate performance status as defined by Lansky or Karnofsky performance status of ≥
             60 (Lansky for <16 years of age).

          3. Life expectancy >12 weeks.

          4. Histological confirmation of neuroblastoma or ganglioneuroblastoma at initial
             diagnosis. Bone marrow samples are acceptable as confirmation of neuroblastoma.

          5. High risk neuroblastoma with persistent/refractory or relapsed disease, defined as:

             • First or greater relapse of neuroblastoma following completion of aggressive
             multi-drug frontline therapy.

             • First episode of progressive neuroblastoma during aggressive multi-drug frontline
             therapy.

               -  Persistent/refractory neuroblastoma as defined by less than a complete response
                  (by the revised INRC) at the conclusion of at least 4 cycles of aggressive
                  multidrug induction chemotherapy on or according to a high-risk neuroblastoma
                  protocol (such as A3973 or ANBL0532).

               -  Patients must be diagnosed with high risk neuroblastoma at initial diagnosis or
                  if non-high risk at time of initial diagnosis must have had evidence of
                  metastatic progression when >18 months of age. (See Section 12.9 for COG and INRG
                  definitions if needed)

          6. Subjects must have measurable or evaluable disease per Revised International
             Neuroblastoma Response Criteria (See Section 12.6)

          7. Adequate central nervous system function as defined by:

               -  No known CNS disease

               -  No seizure disorder requiring antiepileptic drug therapy

          8. Adequate cardiac function as defined by:

             • Shortening fraction of ≥27% by echocardiogram

          9. Adequate pulmonary function as defined by:

             • No chronic oxygen requirement and room air pulse oximetry >94%.

         10. Females of childbearing potential must have a negative serum pregnancy test within 72
             hours prior to cell procurement. NOTE: Premenarchal females do not require pregnancy
             testing.

         11. Females of childbearing potential must be willing to abstain from heterosexual
             activity or to use 2 forms of effective methods of contraception from the time of
             informed consent until 3 months after treatment discontinuation. The two contraception
             methods can be comprised of two barrier methods, or a barrier method plus a hormonal
             method or an intrauterine device that meets <1% failure rate for protection from
             pregnancy in the product label.

         12. Male subjects with female partners must have had a prior vasectomy or agree to use an
             adequate method of contraception (i.e., double barrier method: condom plus spermicidal
             agent) starting with the first dose of study therapy through 3 months after the last
             dose of study therapy.

         13. As determined by the enrolling physician, subject is willing and able to comply with
             study procedures.

        Exclusion Criteria:

        Subjects meeting any of the following exclusion criteria will not be able to participate in
        this study (procurement, lymphodepletion and cell infusion).

          1. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the
             mother is being treated on study).

          2. Has a known additional malignancy that is active and/or progressive requiring
             treatment.

          3. History of hypersensitivity reactions to murine protein-containing products.

          4. History of hypersensitivity to cyclophosphamide or fludarabine.

          5. Systemic steroid use except as below:

               -  Physiologic replacement for adrenal insufficiency is allowed at doses of
                  hydrocortisone 6-12 mg/m2/day or equivalent.

               -  Inhaled steroids are allowed.

               -  Other than the above, systemic steroids must be stopped >14 days prior to
                  procurement, but may be resumed after procurement if needed as per treating
                  physician. Systemic steroids must be stopped 48 hours prior to lymphodepletion
                  and not used after infusion unless clinically required.

          6. Uncontrolled infection requiring systemic therapy.

          7. Subjects are required to be negative for HIV antibody or HIV viral load, negative for
             HTLV1 and 2 antibody or PCR negative for HTLV1 and 2, negative for Hepatitis B surface
             antigen, or negative for HCV antibody or HCV viral load. Tests can be pending at the
             time of cell procurement; only those samples confirming lack of active infection will
             be used to generate transduced cells.

             A. Eligibility criteria to be met prior to procurement A.1 Written informed consent to
             undergo cell procurement signed by legal guardian must be obtained prior to
             procurement. Written assent required as applicable for age <15 years old.

             A.2 Age greater than 18 months and less than 18 years at the time of consent. A.3
             Imaging and bone marrow study results from within 90 days prior to procurement to
             assess presence of active disease.

             A.4 Subjects who have received murine antibodies must have documentation of absence of
             human anti-mouse antibodies (HAMA). Test can be pending at the time of cell
             procurement; only those patients with confirmed absence of HAMA will have cells
             generated.

             A.5 Adequate organ function as defined in the table below; all labs to be obtained
             within 7 days of procurement System Laboratory Value Hematological* Hemoglobin ≥ 9.0
             g/dL, Absolute Neutrophil Count (ANC) ≥ 0.8 x 109/L, Platelets (transfusion
             independent) ≥ 50 x 109/L Renal Age: Maximum Serum Creatinine (mg/dL) (Male, Female) 1
             to <2 years: (≤0.6, ≤0.6); 2 to <6 years:(≤0.8, ≤0.8); 6 to <10 years: (≤1, ≤1); 10 to
             <13 years: (≤1.2, ≤1.2); 13 to <16 years: (≤1.5, ≤1.4); ≥16 years: (≤1.7, ≤1.4)
             Hepatic Total Bilirubin ≤ 1.5 × upper limit of normal (ULN) for age Alanine
             aminotransferase (ALT) ≤ 500 U/L Coagulation International Normalized Ratio (INR) ≤ 2
             × ULN

             *Subjects with known bone marrow involvement are eligible even if they have not met
             the above Hematological eligibility criteria. However, those subjects must be able to
             be supported with transfusions to prevent life-threatening bleeding as per
             investigator discretion.

             B. Eligibility criteria to be met prior to lymphodepletion B.1 Written informed
             consent to enroll in the iC9.GD2.CAR.IL-15 cell therapy trial signed by legal guardian
             must be obtained prior to starting lymphodepletion. Written assent required as
             applicable for age <15 years old.

             B.2 Subjects must have imaging and bone marrow study results within 14 days prior to
             lymphodepletion (used as baseline measure for documentation of progression before the
             lymphodepletion). Subjects who have received bridging chemotherapy must have imaging
             and bone marrow study results at least 3 weeks after most recent therapy. Required is
             anatomic imaging (MRI or CT) and functional imaging with MIBG (or PET if mass is
             MIBG-nonavid). A mass which is neither MIBG-avid nor PET-avid will require biopsy to
             confirm neuroblastoma or ganglioneuroblastoma.

             B.3 Adequate organ function as defined in the table below; all labs to be obtained
             within 7 days of procurement System Laboratory Value Hematological* Hemoglobin ≥ 9.0
             g/dL, Absolute Neutrophil Count (ANC) ≥ 0.8 x 109/L, Platelets (transfusion
             independent) ≥ 50 x 109/L Renal Age: Maximum Serum Creatinine (mg/dL) (Male, Female) 1
             to <2 years: (≤0.6, ≤0.6); 2 to <6 years:(≤0.8, ≤0.8); 6 to <10 years: (≤1, ≤1); 10 to
             <13 years: (≤1.2, ≤1.2); 13 to <16 years: (≤1.5, ≤1.4); ≥16 years: (≤1.7, ≤1.4)
             Hepatic Total Bilirubin ≤ 1.5 × upper limit of normal (ULN) for age Alanine
             aminotransferase (ALT) ≤ 500 U/L

             *Subjects with known bone marrow involvement are eligible even if they have not met
             the above Hematological eligibility criteria. However, those subjects must be able to
             be supported with transfusions to prevent life-threatening bleeding as per
             investigator discretion.

             **Patients with moderate impairment of renal function (normalized creatinine clearance
             30-70 mL/min/1.73m2) should have their fludarabine dose reduced by 20% and be
             monitored closely for excessive toxicity.

             B.4 Treatment with any investigational drug within 21 days of lymphodepletion or any
             tumor vaccines within the previous six weeks prior to lymphodepletion.

             B.5 Adequate performance status as defined by Lansky or Karnofsky performance status
             of ≥ 60 (Lansky for <16 years of age).

             B.6 Females of childbearing potential must have a negative serum pregnancy test within
             72 hours prior to lymphodepletion. NOTE: Premenarchal females do not require pregnancy
             testing.

             B.7 Available autologous transduced activated T cells product meets the certificate of
             analysis.

             B.8 Subject has not received aldesleukin (IL-2) within 28 days of starting
             lymphodepletion.

             B.9 Subject has not received:

             • filgrastim (G-CSF) (or biosimilar) within 7 days of starting lymphodepletion;

             • sargramostim (GM-CSF) within 14 days of starting lymphodepletion;

             • pegfilgrastim within 21 days of starting lymphodepletion.

             B.10 Systemic steroid use is prohibited, except as below:

             • Physiologic replacement for adrenal insufficiency is allowed at doses of
             hydrocortisone 6-12 mg/m2/day or equivalent.

             • Inhaled steroids are allowed.

               -  Other than the above, systemic steroids must be stopped 48 hours prior to
                  lymphodepletion and not used after infusion unless clinically required.

             B.11 Prior autologous stem cell transplant is allowed as long as it occurred ≥4 weeks
             prior to lymphodepletion.

             B.12 Prior therapeutic 131I-MIBG is allowed as long as it is completed ≥4 weeks prior
             to lymphodepletion.

             B.13 Prior anti-GD2 therapy (such as dinutuximab) is allowed as long as it is
             completed ≥4 weeks prior to lymphodepletion.

             B.14 Subject did not have major surgery within 14 days of starting lymphodepletion.

             B.15 Subjects that have received bridging therapy with murine antibodies must have
             documentation of absence of human anti-mouse antibodies (HAMA) prior to
             lymphodepletion.

             B.16 Subject is not taking a prohibited or contraindicated medication listed in
             Section 4.2.11 prior to lymphodepletion. Contraindicated medications should be
             discontinued at least two weeks prior to the scheduled lymphodepletion or by at least
             5 half-lives of the contraindicated medication, whichever is shorter.

             B.17 Subject does not have disease progression that would, in the opinion of the
             treating physician, place the subject at significant potential risk, such as location
             of lesion that would have high risk with tumor swelling (examples include airway or
             spinal canal).

             B.18 No evidence of uncontrolled infection or sepsis.

             C. Eligibility criteria to be met prior to cell infusion after lymphodepletion C.1
             Subject is a good candidate for treatment per investigator's discretion. C.2 No
             evidence of uncontrolled infection or sepsis.

             D. Eligibility Criteria Prior to Lymphodepltion for Second Infusion (Optional) D.1
             Subjects must not have received bridging therapy after their initial iC9.GD2.CAR.IL-15
             cell infusion.

             D.2 Adequate organ function as defined in the table below:

             System Laboratory Value Hematological* Absolute Neutrophil Count (ANC) ≥ 0.8 x 109/L,
             Platelets (transfusion independent) ≥ 50 x 109/L Renal** Age: Maximum Serum Creatinine
             (mg/dL) (Male, Female) 1 to <2 years: (≤0.6, ≤0.6); 2 to <6 years:(≤0.8, ≤0.8); 6 to
             <10 years: (≤1, ≤1); 10 to <13 years: (≤1.2, ≤1.2); 13 to <16 years: (≤1.5, ≤1.4); ≥16
             years: (≤1.7, ≤1.4) Hepatic Total Bilirubin ≤ 1.5 × upper limit of normal (ULN) for
             age Alanine aminotransferase (ALT) ≤ 500 U/L

             *Subjects with known bone marrow involvement are eligible even if they have not met
             the above Hematological eligibility criteria. However, those subjects must be able to
             be supported with transfusions to prevent life-threatening bleeding as per
             investigator discretion.

             **Patients with moderate impairment of renal function (normalized creatinine clearance
             30-70 mL/min/1.73m2) should have their fludarabine dose reduced by 20% and be
             monitored closely for excessive toxicity.

             D.3 Adequate performance status as defined by Lansky or Karnofsky performance status
             of ≥ 60 (Lansky for <16 years of age).

             D.4 Females of childbearing potential must have a negative serum pregnancy test within
             72 hours prior to lymphodepletion. NOTE: Premenarchal females do not require pregnancy
             testing.

             D.5 Subject has not received:

             • filgrastim (G-CSF) (or biosimilar) within 7 days of starting lymphodepletion;

             • sargramostim (GM-CSF) within 14 days of starting lymphodepletion;

             • pegfilgrastim within 21 days of starting lymphodepletion.

             D.6 Systemic steroid use is prohibited, except as below:

               -  Physiologic replacement for adrenal insufficiency is allowed at doses of
                  hydrocortisone 6-12 mg/m2/day or equivalent.

               -  Inhaled steroids are allowed.

               -  Other than the above, systemic steroids must be stopped 48 hours prior to
                  lymphodepletion and not used after infusion unless clinically required.

             D.7 Subject did not have major surgery within 14 days of starting lymphodepletion.

             D.8 Subject is not taking a prohibited or contraindicated medication listed in Section
             4.2.12 prior to lymphodepletion. Contraindicated medications should be discontinued at
             least two weeks prior to the scheduled lymphodepletion or by at least 5 half-lives of
             the contraindicated medication, whichever is shorter.

             D.9 No evidence of uncontrolled infection or sepsis. D.10 Subject has completed the
             initial safety evaluation period without DLTs. D.11 Subject has not experienced
             additional toxicity(ies) directly attributable to the initial T-cell infusion that
             would place them at excessive risk with re-infusion.

             D.12 Subject has derived clinical benefit from the initial infusion as assessed by the
             investigator (stable disease or better to the initial infusion).

             D.13 Subject has sufficient stored iC9.GD2.CAR.IL-15 T-cells for re-infusion.

             E. Eligibility Criteria Prior to Second Infusion (Optional) E.1 Subject is a good
             candidate for treatment per investigator's discretion. E.2 No evidence of uncontrolled
             infection or sepsis.
      
Maximum Eligible Age:18 Years
Minimum Eligible Age:18 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with adverse events as a measure of safety and tolerability of iC9.GD2.CAR.IL-15 T cells administered to pediatric subjects with relapsed or refractory neuroblastoma
Time Frame:4 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) and CRS symptoms will be graded according to criteria outlined in Section 12.4 and neurotoxicity/ICANS will be graded according to criteria outlined in Section 12.5

Secondary Outcome Measures

Measure:Identify the maximum tolerated dose (MTD) of iC9.GD2.CAR.IL-15 T cells administered to pediatric subjects with relapsed or refractory neuroblastoma
Time Frame:4 weeks
Safety Issue:
Description:Tolerability of iC9.GD2.CAR.IL-15 T cells will be assessed by NCI-CTCAE criteria and the CRS grading criteria outlined in Section 12.4 and neurotoxicity/ICANS will be graded according to criteria outlined in Section 12.5
Measure:Expansion and persistence of iC9.GD2.CAR.IL-15 cells in vivo
Time Frame:15 years
Safety Issue:
Description:Persistence of iC9.GD2.CAR.IL-15 T cells in vivo will be determined by quantitative Polymerase chain reaction (PCR) and flow cytometry in peripheral blood samples
Measure:Anti-tumor response rate to iC9.GD2.CAR.IL-15 t cell administration in pediatric subjects with relapsed or refractory neuroblastoma per Revised International Neuroblastoma Response Criteria (INCR)
Time Frame:6 weeks
Safety Issue:
Description:The overall response rate (ORR = complete (CR) + partial (PR) + minor (MR) responses) to iC9.GD2.CAR.IL-15 T cell infusion will be determined using the revised International Neuroblastoma Response Criteria (INRC)
Measure:Overall survival (OS) in pediatric subjects with relapsed or refractory neuroblastoma treated with iC9.GD2.CAR.IL-15 T cells
Time Frame:15 years
Safety Issue:
Description:OS will be measured from the date of administration of iC9.GD2.CAR.IL-15 T cells to the date of death
Measure:Progression free survival (PFS) in pediatric subjects with relapsed or refractory neuroblastoma treated with iC9.GD2.CAR.IL-15 T cells
Time Frame:15 years
Safety Issue:
Description:PFS is defined from the date of administration of iC9.GD2.CAR.IL-15 T cells to the date of signs and symptoms of treatment failure or relapse from CR or PR, or death from any cause.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:UNC Lineberger Comprehensive Cancer Center

Trial Keywords

  • Autologous Chimeric Antigen Receptor (CAR) T Cells
  • Interleukin (IL)-15
  • Disialoganglioside (GD2)
  • Caspase 9
  • Pediatric
  • Rimiducid
  • AP1903
  • modified T cells
  • CAR T

Last Updated

September 12, 2019