RECRUITING

Humanized CD19-Specific CAR T Cells for the Treatment of Patients With Positive Relapsed or Refractory CD19 Positive B-Cell Acute Lymphoblastic Leukemia

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Conditions

Recurrent Acute Lymphoblastic LeukemiaRefractory Acute Lymphoblastic Leukemia

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase Ib trial tests the safety, side effects, and effectiveness of humanized (hu)CD19-chimeric antigen receptor (CAR) T cell therapy in treating patients with CD19 positive B-cell acute lymphoblastic leukemia (ALL) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). CAR T-cell therapy is a treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein, such as CD19, on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the huCD19 positive CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Chemotherapy drugs, such as fludarabine and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. huCD19-CAR T cell therapy may be safe, tolerable and effective in treating patients with relapsed or refractory CD19 positive ALL.

Official Title

Phase Ib Study to Evaluate Humanized CD19-Specific CAR T Cells Following Lymphodepleting Chemotherapy in Adult Patients With Relapsed/Refractory CD19+ B-Cell Acute Lymphoblastic Leukemia

Quick Facts

Study Start:2024-12-15
Study Completion:2026-12-05
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT06447987

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Documented informed consent of the participant
  2. * Agreement to allow the use of archival tissue from diagnostic tumor biopsies.
  3. * If unavailable, exceptions may be granted with study principal investigator (PI) approval
  4. * Note: For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated full consent is processed. However, the research participant is allowed to proceed with lymphodepletion and T cell infusion only after the translated full consent form is signed
  5. * Age: ≥ 18 years
  6. * Eastern Cooperative Oncology Group (ECOG) 0-2 / Karnofsky performance status (KPS) ≥ 70
  7. * Histologically confirmed CD19+ relapsed/refractory ALL with at least 2 prior lines of therapy
  8. * Prior alloHCT \> 100 days prior to enrollment may be considered a prior line of therapy
  9. * Research participants with confirmed 1st or higher relapse of disease by morphology, cytogenetics or molecular, or research participants with refractory or residual disease
  10. * Participants with central nervous system (CNS) involvement by leukemia (CNS2 and CNS3) may be considered eligible after discussions with the study team
  11. * Patients with only MRD+ disease may be eligible
  12. * Patients with isolated extramedullary disease may also be eligible
  13. * Total bilirubin ≤ 2.0 X upper limit of normal (ULN) (unless has Gilbert's disease or related to leukemia involving the liver)
  14. * Aspartate aminotransferase (AST) ≤ 2.5 x ULN (unless related to leukemia involving the liver)
  15. * Alanine aminotransferase (ALT) ≤ 2.5 x ULN (unless related to leukemia involving the liver)
  16. * Creatinine clearance of ≥ 50 mL/min per 24-hour urine test or the Cockcroft-Gault formula
  17. * Left ventricular ejection fraction (LVEF) ≥ 45%
  18. * Note: To be performed within 28 days prior to start of protocol therapy
  19. * Cardiac function (12 lead-electrocardiogram \[ECG\]): Corrected QT interval (QTc) must be ≤ 480 msec
  20. * Oxygen (O2) saturation \> 92% on room air
  21. * Note To be performed within 28 days prior to start of protocol therapy
  22. * Seronegative for HIV quantitative polymerase chain reaction (qPCR), hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin \[RPR\])
  23. * If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed. OR
  24. * If seropositive for HIV, HCV or HBV, nucleic acid quantitation must be performed. The viral load must be undetectable
  25. * Meets other institutional and federal requirements for infectious disease titer requirements
  26. * Note Infectious disease testing to be performed within 28 days prior to start of protocol therapy
  27. * Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  28. * Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy
  29. * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)
  30. * ELIGIBILITY TO PROCEED WITH PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC) COLLECTION FOR CAR T CELL MANUFACTURING
  31. * Research participant has signed the 'screening and leukapheresis' informed consent
  32. * Research participant must have appropriate venous access, have a central line or be willing to undergo central or temporary line placement
  33. * The last dose of systemic chemotherapy must be at least 2 weeks before the leukapheresis procedure with the following exceptions:
  34. * Steroids and vincristine are allowed up to 7 days prior to leukapheresis.
  35. * Intrathecal chemotherapy is allowed up to 3 days prior to leukapheresis.
  36. * Tyrosine kinase inhibitors are allowed up to 48 hours prior to leukapheresis.
  37. * Hydrea is allowed up to 48 hours prior to leukapheresis.
  38. * The research participant cannot be on ≥ 7.5 mg prednisone or equivalent doses of other corticosteroids at the time of leukapheresis. Note: Topical and inhaled corticosteroids in standard doses and physiologic replacement for subjects with adrenal insufficiency are allowed
  39. * The last dose of prior targeted agents, immunotherapy or radiation must be at least 2 weeks before the leukapheresis procedure
  40. * If the research participant has undergone prior alloHCT, 100 days must have elapsed since allogeneic stem cell transplant to undergo PBMC collection for CAR T cell manufacturing
  41. * ELIGIBILITY TO UNDERGO LYMPHODEPLETION
  42. * Research participant's absolute leukemic blast count does not exceed 10,000 cells/uL
  43. * The last dose of chemotherapy, maintenance therapy, radiation therapy, biological therapy, and/or immunotherapy must have been 7 days prior to start of lymphodepletion
  44. * The following washout periods must be met:
  45. * Corticosteroids 3 days
  46. * Biologic agents 3 half lives
  47. * Oral chemotherapeutic agents 3 half lives
  48. * Intrathecal chemotherapy 3 days
  49. * Chemo and/or immunotherapy 2 weeks
  50. * Local radiation to sites 7 days
  51. * Non myeloablative agents 7 days
  52. * Investigational agents 2 weeks, or at least 3 half lives
  53. * Hydroxyurea no washout period
  54. * Research participant has a released cryopreserved CAR T cell product for CAR T cell infusion on approximately day 0 (performed no more than 7 days prior to start of lymphodepletion)
  55. * ECOG \< 2 / KPS ≥ 70 (performed no more than 7 days prior to start of lymphodepletion)
  56. * No ongoing post treatment ≥ grade 3 non-heme toxicities (with exception of grade 3 glucose intolerance, cholesterol, triglyceride, peripheral neuropathy, and hyperglycemia) (performed no more than 7 days prior to start of lymphodepletion)
  57. * Research participant does not require supplemental oxygen to keep saturation greater than or equal to 92% and/or does not have any radiographic abnormalities on chest x-ray that are progressive (performed no more than 7 days prior to start of lymphodepletion)
  58. * Research participant does not require pressor support and/or does not have symptomatic cardiac arrhythmias (performed no more than 7 days prior to start of lymphodepletion)
  59. * Research participant does not have a fever exceeding 38.5 degree Celsius (C); there is an absence of positive blood cultures for bacteria, fungus, or virus within 48-hours prior to lymphodepletion and/or there aren't any indications of meningitis (performed no more than 7 days prior to start of lymphodepletion)
  60. * Research participant serum total bilirubin does not exceed 2.5X normal limit or transaminases do not exceed 3X normal limit unless related to underlying leukemia (to be discussed at the discretion of the PI/study team) (performed no more than 7 days prior to start of lymphodepletion)
  61. * Note: in the event a participant has elevated levels of liver enzymes possibly related to underlying disease/disease progression, the participant will still be considered eligible
  62. * Research participant serum creatinine ≤ 2 mg/dL (performed no more than 7 days prior to start of lymphodepletion)
  63. * Research participant does not have uncontrolled seizure activity (performed no more than 7 days prior to start of lymphodepletion)
  64. * ELIGIBILITY TO PROCEED WITH CAR T CELL INFUSION
  65. * No ongoing post treatment ≥ grade 3 non-heme toxicities (with exception of grade 3 glucose intolerance, cholesterol, triglyceride, peripheral neuropathy, and hyperglycemia)
  66. * Prednisone (or prednisone equivalent) dose of ≤ 7.5 mg/kg/day is allowed
  67. * Prohibited medications have not been administered
  68. * KPS ≥ 70
  69. * No untreated or active systemic infection
  70. * No Class III/IV cardiovascular disability according to the NYHA Classification
  71. * Research participant does not require supplemental oxygen to keep saturation greater than or equal to 92% and/or does not have any radiographic abnormalities on chest x-ray that are progressive
  72. * Research participant does not require pressor support and/or does not have symptomatic cardiac arrhythmias
  73. * Research participant does not have a fever exceeding 38.5 degree C; there is an absence of positive blood cultures for bacteria, fungus, or virus within 48-hours prior to T cell infusion and/or there aren't any indications of meningitis
  74. * Research participant serum total bilirubin does not exceed 2.5X normal limit or transaminases do not exceed 3X normal limit unless related to underlying leukemia (to be discussed at the discretion of the PI/study team)
  75. * Research participant serum creatinine ≤ 2 mg/dL
  76. * Research participant does not have uncontrolled seizure activity
  77. * ELIGIBILITY TO PROCEED WITH OPTIONAL CAR T CELL ABLATION
  78. * Research participant has \> 1% CAR T cells in the peripheral blood
  79. * No known hypersensitivity to cetuximab
  80. * Not requiring supplemental oxygen or mechanical ventilation, oxygen saturation 92% or higher on room air
  81. * Not requiring pressor support, no symptomatic cardiac arrhythmias, no acute coronary syndrome, or uncontrolled hypertension
  82. * Serum creatinine did NOT increase by more than 2.5 fold from base line (at time of screening )
  83. * Adequate liver function defined as total bilirubin \< 3.0 mg/dl, AST \< 5 x ULN; ALT \< 5 x ULN
  84. * Research participant without clinically significant encephalopathy/new focal deficits
  85. * No clinical evidence of uncontrolled active infectious process
  1. * Allogeneic stem cell transplant within 100 days at the time of enrollment
  2. * Received prior CAR T therapy within 90 days of enrollment
  3. * EXCEPTION: Participants who have previously received B-cell-activating factor receptor (BAFFR)-CAR T cells will be excluded from this study
  4. * Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I study
  5. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent(s)
  6. * History or presence of clinically relevant CNS pathology such as uncontrolled seizure disorder, recent stroke, severe brain injuries, dementia, cerebellar disease or psychosis
  7. * Autoimmune disease or active graft versus host disease (GVHD) requiring systemic immunosuppressant therapy
  8. * Class III/IV cardiovascular disability according to the New York Heart Association (NYHA) Classification
  9. * History of other malignancies, except for malignancy surgically resected (or treated with other modalities) with curative intent, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; non-muscle invasive bladder cancer; malignancy treated with curative intent with no known active disease present for ≥ 2 years
  10. * Clinically significant uncontrolled illness
  11. * Active systemic uncontrolled infection requiring antibiotics
  12. * Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
  13. * Subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR) result. Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded
  14. * Subjects who are hepatitis B core antibody positive (or have a known history of HBV infection) should be monitored quarterly with a quantitative PCR test for HBV deoxyribonucleic acid (DNA). HBV monitoring should last until 12 months after the last dose of study drug. Any subject with a rising viral load (above lower limit of detection) should discontinue study drug and have antiviral therapy instituted and a consultation with a physician with expertise in managing hepatitis B. Subjects who are core antibody (Ab) positive at study enrollment are strongly recommended to start Entecavir before start and until completion of study treatment
  15. * Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded
  16. * Females only: Pregnant or breastfeeding
  17. * Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of topical or inhaled steroids is not exclusionary. Physiologic replacement of steroids (prednisone ≤ 7.5 mg /day or equivalent) is allowed
  18. * Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
  19. * Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Contacts and Locations

Principal Investigator

Ibrahim Aldoss
PRINCIPAL_INVESTIGATOR
City of Hope Medical Center

Study Locations (Sites)

City of Hope Medical Center
Duarte, California, 91010
United States

Collaborators and Investigators

Sponsor: City of Hope Medical Center

  • Ibrahim Aldoss, PRINCIPAL_INVESTIGATOR, City of Hope Medical Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-12-15
Study Completion Date2026-12-05

Study Record Updates

Study Start Date2024-12-15
Study Completion Date2026-12-05

Terms related to this study

Additional Relevant MeSH Terms

  • Recurrent Acute Lymphoblastic Leukemia
  • Refractory Acute Lymphoblastic Leukemia