RECRUITING

CD19/CD22 Bicistronic Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory CD19/CD22-expressing B Cell Malignancies

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Conditions

B-NHLB-Non Hodgkin LymphomaAcute Lymphocytic LeukemiaAcute Lymphoblastic LeukemiaB-precursor ALLB-AllLymphoma, Non-HodgkinLeukemia, Lymphocytic, B CellB-Cell LymphomaB-Cell LeukemiaAcute Lymphoid LeukemiaPhiladelphia chromosome + ALLLymphomaCD-22 Expressing TumorCD-19 expressing tumorAdoptive Immunotherapy

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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

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer in children. About 90% of children and young adults who are treated for ALL can now be cured. But if the disease comes back, the survival rate drops to less than 50%. Better treatments are needed for ALL relapses. Objective: To test chimeric antigen receptor (CAR) therapy. CARs are genetically modified cells created from each patient s own blood cells. his trial will use a new type of CAR T-cell that is targeting both CD19 and CD22 at the same time. CD19 and CD22 are proteins found on the surface of most types of ALL. Eligibility: People aged 3 to 39 with ALL or related B-cell lymphoma that has not been cured by standard therapy. Design: Participants will be screened. This will include: Physical exam Blood and urine tests Tests of their lung and heart function Imaging scans Bone marrow biopsy. A large needle will be inserted into the body to draw some tissues from the interior of a bone. Lumbar puncture. A needle will be inserted into the lower back to draw fluid from the area around the spinal cord. Participants will undergo apheresis. Their blood will circulate through a machine that separates blood into different parts. The portion containing T cells will be collected; the remaining cells and fluids will be returned to the body. The T cells will be changed in a laboratory to make them better at fighting cancer cells. Participants will receive chemotherapy starting 4 or 5 days before the CAR treatment. Participants will be admitted to the hospital. Their own modified T cells will be returned to their body. Participants will visit the clinic 2 times a week for 28 days after treatment. Follow-up will continue for 15 years....

Official Title

Phase 1/2 Dose Escalation Study of CD19/CD22 Bicistronic Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory CD19/CD22-expressing B Cell Malignancies

Quick Facts

Study Start:2022-12-28
Study Completion:2029-07-01
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT05442515

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:3 Years to 39 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:CHILD, ADULT
Inclusion CriteriaExclusion Criteria
  1. * Diagnosis
  2. * Participant must:
  3. * Have pathology confirmed B cell ALL (not isolated to the testis or CNS), CML with ALL transformation, or high-grade lymphoma (e.g., Burkitt s lymphoma, B-lymphoblastic lymphoma, diffuse large B-cell lymphoma, inclusive of low-grade lymphoma that has transformed to high grade disease); and
  4. * Have relapsed or been refractory after at least one standard chemotherapy regimen and at least one salvage treatment. Participants with Philadelphia chromosome + ALL must have failed prior tyrosine kinase inhibitor; and
  5. * Be ineligible for allogeneic stem cell transplant (SCT), have refused SCT, or have recurred after SCT; and
  6. * Have no evidence of graft-versus- host disease (GVHD) and have been without immunosuppressive agents for at least 30 days prior to apheresis, if undergone prior allogeneic SCT; and
  7. * Be unable to access (in a timely manner), ineligible for, or have relapsed/failed after or not responded to a commercially available CD19 CAR T-cell construct; and
  8. * Have evidence of at least minimal residual disease or PET-avid disease (lymphoma) at the time of enrollment.
  9. * CD22/CD19 expression
  10. * CD19 must be detected on \>15% of the malignant cells by immunohistochemistry or \> 80% by flow cytometry.
  11. * CD22 positivity must be confirmed.
  12. * Age \>= 3 years of age and \<=39 years of age at time of enrollment.
  13. * Clinical Performance status: Participants \>= 16 years of age: Karnofsky \>= 50%; Participants \< 16 years of age: Lansky scale \>= 50%.
  14. * Participants must have adequate organ and marrow function as defined below:
  15. * leukocytes \>= 750/mcL\*
  16. * platelets \>= 50,000/mcL\*
  17. * total bilirubin \<=2 X ULN (except in the case of participants with documented Gilbert s disease \> 3x ULN)
  18. * AST(SGOT)/ALT(SGPT) \<=10 x institutional upper limit of normal
  19. * creatinine \<= the maximum for age listed in the table below OR
  20. * measured creatinine clearance \>=60 mL/min/1.73 m\^2 for participants with creatinine levels above the max listed below per age.
  21. * Age (Years) \<= 5 \|\| Maximum Serum Creatinine (mg/dL) \<= 0.8
  22. * Age (Years) 6 to \<= 10 \|\| Maximum Serum Creatinine (mg/dL) \<= 1.0
  23. * Age (Years) \>10 \|\| Maximum Serum Creatinine (mg/dL) \<= 1.2
  24. * a participant will not be excluded because of pancytopenia \>= Grade 3 if it is due to underlying bone marrow involvement by leukemia
  25. * Central nervous system (CNS) Status
  26. * Participants with leukemia with CNS 1 and 2 disease are eligible in the absence of exclusion criteria
  27. * Participants of child-bearing or child-fathering potential must be willing to practice effective birth control from the time of enrollment until 12 months following completion of study treatment for women and for 4 months following completion of study treatment for men.
  28. * Participants who are breastfeeding or plan to breastfeed must agree to discontinue/postpone breastfeeding while on study therapy and until 1 month after the administration of CAR.
  29. * Cardiac function: Left ventricular ejection fraction \>= 45% or fractional shortening \>=28%
  30. * Pulmonary Function
  31. * Baseline oxygen saturation \>92% on room air at rest
  32. * Ability of participant or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.
  33. * Ability and willingness of participant or Legally Authorized Representative (LAR) to co- enroll on 15-C-0028: Follow-up Evaluation for Gene-Therapy Related Delayed Adverse Events after Participation in Pediatric Oncology Branch Clinical Trials.
  1. * Participants with CNS3 disease, neurologic signs of CNS disease, radiologically detected active CNS lymphoma
  2. * Hyperleukocytosis (\>= 50,000 blasts/microL)
  3. * Positive serum or urine beta-HCG pregnancy test performed at screening.
  4. * Participants will be excluded based on prior therapy if they fail to meet following washout criteria:
  5. * Therapy: Systemic Chemotherapy, anti-neoplastic agents, antibody- based therapies
  6. * Washout\*: \>=2 weeks
  7. * Exceptions: 6 weeks for clofarabine or nitrosoureas; No washout for prior intrathecal chemotherapy, steroid therapy, hydroxyurea (no dose increases within prior 2 weeks) or ALL maintenance-type chemotherapy (vincristine, 6-mercaptopurine, oral methotrexate, or a tyrosine kinase inhibitor for participants with Ph+ ALL) provided there is recovery from any acute toxic effects
  8. * Therapy: Radiation
  9. * Washout\*: \>=3 weeks
  10. * Exceptions: No time restriction with radiation therapy if the volume of bone marrow treated is less than 10% and the participant has measurable/evaluable disease outside the radiation window
  11. * Therapy: Allogeneic Stem Cell Transplant
  12. * Washout\*: \>= 100 days since SCT; \>= 30 days since completion of immunosuppression; \>= 6 weeks since donor lymphocyte infusion (DLI)
  13. * Exceptions: Cannot have evidence of active graft-versus-host disease (GVHD)
  14. * Therapy: CAR T-Cell Therapy or other Adoptive Cell Therapy
  15. * Washout\*: \> 30 days post infusion
  16. * Exceptions: For patients previously treated with CAR T-cells without interim HSCT (cohorts B1 and D1) cannot have circulating CAR T cells (or genetically modified cells) \>5% by flow cytometry in peripheral blood
  17. * Washout: Time between therapy and apheresis
  18. * Positive HIV antibodies consistent with active HIV.
  19. * Positive hepatitis C antibodies or positive Hepatitis B surface antigen (HbsAG) indicative of current/active HCV/HBV.
  20. * Active second malignancy other than in situ carcinoma of the cervix, unless the tumor was treated with curative intent at least two years previously and participant is in remission.
  21. * History of severe, immediate hypersensitivity reaction attributed to compounds of similar chemical or biologic composition to any agents used in study or in the manufacturing of the cells.
  22. * Uncontrolled, symptomatic, intercurrent illness or social situations that would limit compliance with study requirements or in the opinion of the PI would pose an unacceptable risk to the participant.

Contacts and Locations

Study Contact

NCI Pediatric Leukemia, Lymphoma Transpl
CONTACT
(240) 760-6970
ncilltct@mail.nih.gov
Nirali N Shah, M.D.
CONTACT
(240) 760-6970
shahnn@mail.nih.gov

Principal Investigator

Nirali N Shah, M.D.
PRINCIPAL_INVESTIGATOR
National Cancer Institute (NCI)

Study Locations (Sites)

National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

  • Nirali N Shah, M.D., PRINCIPAL_INVESTIGATOR, National Cancer Institute (NCI)

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 Date2022-12-28
Study Completion Date2029-07-01

Study Record Updates

Study Start Date2022-12-28
Study Completion Date2029-07-01

Terms related to this study

Keywords Provided by Researchers

  • Philadelphia chromosome + ALL
  • Lymphoma
  • CD-22 Expressing Tumor
  • CD-19 expressing tumor
  • Adoptive Immunotherapy
  • B-All
  • B-precursor ALL
  • Acute Lymphoblastic Leukemia
  • Acute Lymphocytic Leukemia
  • B-Non Hodgkin Lymphoma

Additional Relevant MeSH Terms

  • B-NHL
  • B-Non Hodgkin Lymphoma
  • Acute Lymphocytic Leukemia
  • Acute Lymphoblastic Leukemia
  • B-precursor ALL
  • B-All
  • Lymphoma, Non-Hodgkin
  • Leukemia, Lymphocytic, B Cell
  • B-Cell Lymphoma
  • B-Cell Leukemia
  • Acute Lymphoid Leukemia