Study of B7-H3-Specific CAR T Cell Locoregional Immunotherapy for Diffuse Intrinsic Pontine Glioma/Diffuse Midline Glioma and Recurrent or Refractory Pediatric Central Nervous System Tumors

Learn more about:
Related Clinical Trial
A Phase II Trial Evaluating the Efficacy of Cabozantinib With Patients With Refractory GCTs Maintenance Oral Etoposide or Observation Following High-dose Chemo for GCT A Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors A Study of a New Way to Treat Children With a Brain Tumor Called NGGCT Aerosolized Azacytidine as Epigenetic Priming for Bintrafusp Alfa-Mediated Immune Checkpoint Blockade in Patients With Unresectable Pulmonary Metastases From Sarcomas, Germ Cell Tumors, or Epithelial Malignancies B7H3 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults Symptom Management for YA Cancer Survivors A Study of miRNA 371 in Patients With Germ Cell Tumors Vorinostat in Combination With Chemotherapy in Relapsed/Refractory Solid Tumors and CNS Malignancies Interleukin-15 Armored Glypican 3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric CNS Tumors HER2-specific CAR T Cell Locoregional Immunotherapy for HER2-positive Recurrent/Refractory Pediatric CNS Tumors Study of B7-H3-Specific CAR T Cell Locoregional Immunotherapy for Diffuse Intrinsic Pontine Glioma/Diffuse Midline Glioma and Recurrent or Refractory Pediatric Central Nervous System Tumors Aflac ST0901 CHOANOME – Sirolimus in Solid Tumors Study of Genistein in Pediatric Oncology Patients (UVA-Gen001) A Pilot RCT of the PRISM Intervention for AYAs With Cancer Simvastatin With Topotecan and Cyclophosphamide in Relapsed and/or Refractory Pediatric Solid and CNS Tumors Molecular-Guided Therapy for Childhood Cancer EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults A Study of CD45RA+ Depleted Haploidentical Stem Cell Transplantation in Children With Relapsed or Refractory Solid Tumors and Lymphomas Recombinant Human Thrombopoietin in Children Receiving Ifosfamide, Carboplatin, and Etoposide Chemotherapy MR-guided High Intensity Focused Ultrasound (HIFU) on Pediatric Solid Tumors Tandem Peripheral Blood Stem Cell (PBSC) Rescue for High Risk Solid Tumors Amifostine to Protect From Side Effects of PSCT in Treating Patients With Solid Tumors Talabostat Combined With Temozolomide or Carboplatin in Treating Young Patients With Relapsed or Refractory Brain Tumors or Other Solid Tumors Auto Transplant for High Risk or Relapsed Solid or CNS Tumors Busulfan in Treating Children and Adolescents With Refractory CNS Cancer CpG 7909 in Treating Patients Who Have Undergone Autologous Stem Cell Transplant Development of Strategies to Increase Enrollment in Clinical Trials for Children With Cancer Ixabepilone in Treating Young Patients With Solid Tumors or Leukemia That Haven’t Responded to Therapy ABT-751 in Treating Young Patients With Refractory Solid Tumors Temozolomide and O6-benzylguanine in Treating Children With Solid Tumors Arsenic Trioxide in Treating Patients With Advanced Neuroblastoma or Other Childhood Solid Tumors Temozolomide Plus Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Malignant Glioma or Recurrent CNS or Other Solid Tumors Collecting and Storing Tissue From Young Patients With Cancer Combination Chemotherapy Followed by Bone Marrow Transplantation in Treating Patients With Rare Cancer High-Dose Thiotepa Plus Peripheral Stem Cell Transplantation in Treating Patients With Refractory Solid Tumors Peripheral Stem Cell Transplantation Plus Chemotherapy in Treating Patients With Malignant Solid Tumors Living After a Rare Cancer of the Ovary: Chronic Fatigue, Quality of Life and Late Effects of Chemotherapy Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant Solid Tumors Everolimus in Refractory Testicular Germ Cell Cancer Studying Genes in Samples From Younger Patients With Ovarian or Testicular Sex Cord Stromal Tumors Adolescent and Young Adult Cancer Patients: Cognitive Toxicity on Survivorship (ACTS) A Phase I Study of Lyso-thermosensitive Liposomal Doxorubicin and MR-HIFU for Pediatric Refractory Solid Tumors Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors First Line TIP in Poor Prognosis TGCTs. Sodium Thiosulfate in Preventing Hearing Loss in Young Patients Receiving Cisplatin for Newly Diagnosed Germ Cell Tumor, Hepatoblastoma, Medulloblastoma, Neuroblastoma, Osteosarcoma, or Other Malignancy Electroacupuncture in Treating Delayed Nausea and Vomiting in Patients Receiving Chemotherapy For Newly Diagnosed Childhood Sarcoma, Neuroblastoma, Nasopharyngeal Cancer, Germ Cell Tumors, or Hodgkin Lymphoma Disulfiram and Cisplatin in Refractory TGCTs. Role of Axumin PET Scan in Germ Cell Tumor Evaluating Immune Therapy, Duravalumab (MEDI4736) With Tremelimumab for Relapsed/Refractory Germ Cell Tumors Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) Neoadjuvant Chemotherapy With or Without Second-Look Surgery Followed by Radiation Therapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Intracranial Germ Cell Tumors Study of the Hypomethylating Drug Guadecitabine (SGI-110) Plus Cisplatin in Relapsed Refractory Germ Cell Tumors Active Surveillance, Bleomycin, Carboplatin, Etoposide, or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors Combination Chemotherapy Plus Amifostine in Treating Children With Malignant Germ Cell Tumors Study Evaluating the Impact of Short Message Service on Compliance With Surveillance of Patients With Germ-cell Tumors Rolapitant Plus Olanzapine in Multiday Cisplatin Chemotherapy Aprepitant + a 5HT3 + Dexamethasone in Patients With Germ Cell Tumors Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients With Relapsed or Refractory Germ Cell Tumors Treatment Outcome and Quality of Life in Patients With Pediatric Extra-Cranial Germ Cell Tumors Previously Treated on Clinical Trial CCLG-GC-1979-01 or CCLG-GC-1989-01 Brentuximab Vedotin in Relapsed/Refractory Germ Cell Tumors Durvalumab Alone or With Tremelimumab in Refractory Germ Cell Tumors Etoposide, Carboplatin, and Bleomycin in Treating Young Patients Undergoing Surgery For Malignant Germ Cell Tumors Studying Biomarkers in Samples From Younger Patients With Malignant Germ Cell Tumor Progression Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Germ Cell Tumors Observation and/or Combination Chemotherapy After Surgery or Biopsy in Treating Young Patients With Extracranial Germ Cell Tumors Conventional Dose Versus High Dose Sequential Chemotherapy for Poor Prognosis Germ Cell Tumors Pazopanib in Advanced and Cisplatin-resistant Germ Cell Tumors Combination Chemotherapy in Treating Children With Newly Diagnosed Malignant Germ Cell Tumors Accelerated v’s Standard BEP Chemotherapy for Patients With Intermediate and Poor-risk Metastatic Germ Cell Tumours Phase II Study of Cisplatin Plus Epirubicin Salvage Chemo in Refractory Germ Cell Tumors Salvage Chemotherapy for Poor Prognosis Germ Cell Tumors Autologous Peripheral Blood Stem Cell Transplant for Germ Cell Tumors Dose Intensification Study in Refractory Germ Cell Tumors With Relapse and Bad Prognosis A Novel Single Arm Phase II Study for Relapsed Germ Cell Tumours With Poor Prognosis Combination Chemotherapy With or Without Bone Marrow or Stem Cell Transplantation in Treating Men With Untreated Germ Cell Tumors Paclitaxel, Ifosfamide and Cisplatin (TIP) Versus Bleomycin, Etoposide and Cisplatin (BEP) for Patients With Previously Untreated Intermediate- and Poor-risk Germ Cell Tumors Study of Brentuximab Vedotin And Bevacizumab In Refractory CD-30 Positive Germ Cell Tumors Nivolumab in Platinum Recurrent or Refractory Metastatic Germ Cell Tumors Proton Beam Radiation Therapy for Central Nervous System (CNS) Germ Cell Tumors Germ Cell Tumor and Testicular Tumor DNA Registry A Phase II Study of Sirolimus and Erlotinib in Recurrent/Refractory Germ Cell Tumors Trial of Gemcitabine, Cisplatin, and Ifosfamide in Patients With Relapsed Non-Seminomatous Germ-Cell Tumors

Brief Title

Study of B7-H3-Specific CAR T Cell Locoregional Immunotherapy for Diffuse Intrinsic Pontine Glioma/Diffuse Midline Glioma and Recurrent or Refractory Pediatric Central Nervous System Tumors

Official Title

Phase 1 Study of B7-H3-Specific CAR T Cell Locoregional Immunotherapy for Diffuse Intrinsic Pontine Glioma/Diffuse Midline Glioma and Recurrent or Refractory Pediatric Central Nervous System Tumors

Brief Summary

      This is a Phase 1 study of central nervous system (CNS) locoregional adoptive therapy with
      autologous CD4+ and CD8+ T cells lentivirally transduced to express a B7H3-specific chimeric
      antigen receptor (CAR) and EGFRt. CAR T cells are delivered via an indwelling catheter into
      the tumor resection cavity or ventricular system in children and young adults with diffuse
      intrinsic pontine glioma (DIPG), diffuse midline glioma (DMG), and recurrent or refractory
      CNS tumors.

      A child or young adult meeting all eligibility criteria, including having a CNS catheter
      placed into the tumor resection cavity or into their ventricular system, and meeting none of
      the exclusion criteria, will have their T cells collected. The T cells will then be
      bioengineered into a second-generation CAR T cell that targets B7H3-expressing tumor cells.
      Patients will be assigned to one of 3 treatment arms based on location or type of their
      tumor. Patients with supratentorial tumors will be assigned to Arm A, and will receive their
      treatment into the tumor cavity. Patients with either infratentorial or
      metastatic/leptomeningeal tumors will be assigned to Arm B, and will have their treatment
      delivered into the ventricular system. The first 3 patients enrolled onto the study must be
      at least 15 years of age and assigned to Arm A or Arm B. Patients with DIPG will be assigned
      to Arm C and have their treatment delivered into the ventricular system. The patient's newly
      engineered T cells will be administered via the indwelling catheter for two courses. In the
      first course patients in Arms A and B will receive a weekly dose of CAR T cells for three
      weeks, followed by a week off, an examination period, and then another course of weekly doses
      for three weeks. Patients in Arm C will receive a dose of CAR T cells every other week for 3
      weeks, followed by a week off, an examination period, and then dosing every other week for 3
      weeks. Following the two courses, patients in all Arms will undergo a series of studies
      including MRI to evaluate the effect of the CAR T cells and may have the opportunity to
      continue receiving up to a total of six courses of CAR T cells if the patient has not had
      adverse effects and if more of their T cells are available.

      The hypothesis is that an adequate amount of B7H3-specific CAR T cells can be manufactured to
      complete two courses of treatment with 3 or 2 doses given on a weekly schedule followed by
      one week off in each course. The other hypothesis is that B7H3-specific CAR T cells can
      safely be administered through an indwelling CNS catheter or delivered directly into the
      brain via indwelling catheter to allow the T cells to directly interact with the tumor cells
      for each patient enrolled on the study. Secondary aims of the study will include evaluating
      CAR T cell distribution with the cerebrospinal fluid (CSF), the extent to which CAR T cells
      egress or traffic into the peripheral circulation or blood stream, and, if tissues samples
      from multiple timepoints are available, also evaluate disease response to B7-H3 CAR T cell
      locoregional therapy.
    


Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Establish the safety, defined by the adverse events, of B7H3-specific CAR T cell infusions delivered by a central nervous system (CNS) catheter into the tumor resection cavity or ventricular system

Secondary Outcome

 Assess the distribution of CNS-delivered B7H3-specific CAR T cells distribution within the cerebrospinal fluid (CSF) and peripheral blood

Condition

Central Nervous System Tumor

Intervention

SCRI-CARB7H3(s); B7H3-specific chimeric antigen receptor (CAR) T cel

Study Arms / Comparison Groups

 ARM A (Tumor Cavity Infusion)
Description:  Patients with non-DIPG supratentorial tumors for which CAR T cells will be delivered into the tumor resection cavity

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

70

Start Date

December 11, 2019

Completion Date

May 2041

Primary Completion Date

May 2026

Eligibility Criteria

        Inclusion Criteria:

          1. Age ≥ 1 and ≤ 26 years

          2. Diagnosis of refractory or recurrent CNS disease for which there is no standard
             therapy, or diagnosis of DIPG or DMG at any time point following completion of
             standard therapy

          3. Able to tolerate apheresis, or has apheresis product available for use in
             manufacturing

          4. CNS reservoir catheter, such as an Ommaya or Rickham catheter

          5. Life expectancy ≥ 8 weeks

          6. Lansky or Karnofsky score ≥ 60

          7. If patient does not have previously obtained apheresis product, patient must have
             discontinued, and recovered from acute toxic effects of, all prior chemotherapy,
             immunotherapy, and radiotherapy and discontinue the following prior to enrollment:

               1. ≥ 7 days post last chemotherapy/biologic therapy administration

               2. 3 half lives or 30 days, whichever is shorter post last dose of anti-tumor
                  antibody therapy

               3. Must be at least 30 days from most recent cellular infusion

               4. All systemically administered corticosteroid treatment therapy must be stable or
                  decreasing within 1 week prior to enrollment with maximum dexamethasone dose of
                  2.5 mg/m2/day. Corticosteroid physiologic replacement therapy is allowed.

          8. Adequate organ function

          9. Adequate laboratory values

         10. Patients of childbearing/fathering potential must agree to use highly effective
             contraception

        Exclusion Criteria:

          1. Presence of Grade ≥ 3 cardiac dysfunction or symptomatic arrhythmia requiring
             intervention

          2. Presence of primary immunodeficiency/bone marrow failure syndrome

          3. Presence of clinical and/or radiographic evidence of impending herniation

          4. Presence of >Grade 3 dysphagia

          5. Presence of active malignancy other than the primary CNS tumor under study

          6. Presence of active severe infection

          7. Receiving any anti-cancer agents or chemotherapy

          8. Pregnant or breastfeeding

          9. Subject and/or authorized legal representative unwilling or unable to provide
             consent/assent for participation in the 15 year follow up period

         10. Presence of any condition that, in the opinion of the investigator, would prohibit the
             patient from undergoing treatment under this protocol
      

Gender

All

Ages

1 Year - 26 Years

Accepts Healthy Volunteers

No

Contacts

Nick Vitanza, MD, 206-987-2106, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04185038

Organization ID

BrainChild-03


Responsible Party

Principal Investigator

Study Sponsor

Seattle Children's Hospital


Study Sponsor

Nick Vitanza, MD, Study Chair, Seattle Children's Hospital


Verification Date

March 2021