RECRUITING

BAFFR Targeting CAR-T Cells for the Treatment of Relapsed or Refractory B-cell ALL

Conditions

Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia B cell ALL relapsed or refractory

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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

A Phase 1 Study Evaluating BAFFR-targeting CAR T Cells for Patients with Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia

Official Title

A Phase 1 Study Evaluating BAFFR-targeting CAR T Cells for Patients With Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia

Quick Facts

Study Start:2021-05-18

Study Completion:2027-11-18

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04690595

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 Criteria	Exclusion Criteria
1. Documented informed consent of the participant and/or legally authorized representative. 2. Agreement to allow the use of archival tissue from diagnostic tumor biopsies. If unavailable, exceptions may be granted with study PI approval. 3. Age ≥ 18 years. 4. ECOG ≤ 2. 5. Life expectancy ≥ 16 weeks. 6. Histologically confirmed B-ALL or B-cell lymphoblastic lymphoma 7. Relapsed/refractory disease after failure of ≥ 2 prior lines of therapy. 8. Evidence of active BAFF-R expression at the time of enrollment. 9. Recovered to ≤ Grade 1 from the acute toxic effects (except alopecia) of prior anti-cancer therapy. 10. No known contraindications to leukapheresis, steroids or tocilizumab. 11. Ineligible for or failed prior CD19-targeted immunotherapy (e.g., blinatumomab or CD19-CAR T cells). 12. Participants with CNS involvement by leukemia (CNS2 and asymptomatic CNS3) may be considered eligible after discussions with the study team. 13. Total serum bilirubin ≤ULN (unless has Gilbert's disease, then ≤3.0) 14. AST ≤ ULN 15. ALT ≤ ULN 16. Creatinine clearance of ≥ 40 mL/min per 24-hour urine test or the Cockcroft-Gault formula 17. Left ventricular ejection fraction (LVEF) ≥ 50% 18. O2 saturation ≥ 92% on room air. 19. Seronegative for HIV Ag/Ab combo, HCV\, and active HBV (Surface Antigen Negative) 20. 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. 21. QuantiFERON-TB Gold or equivalent\ 22. 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 3 months after the last dose of protocol therapy. 23. A complete liver evaluation (which includes ultrasound elastography, MRI of the liver and a hepatology consult) may be done if needed based on PI's recommendation. 24. Evaluation of acquired hemochromatosis (indicated through MRI of the liver and elevated levels of Ferritin) is recommended for participants who have undergone multiple transfusions and prior alloHCT.	1. Autologous/allogeneic stem cell transplant within 100 days at the time of enrollment. 2. Immunosuppressant medications within 1 months prior to protocol enrollment. 3. Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. Physiologic replacement of steroids (prednisone ≤ 7.5 mg /day or equivalent) is allowed 4. Auto-immune disease or active GVHD within 4 months prior to protocol enrollment requiring systemic immunosuppressant therapy. 5. Class III/IV cardiovascular disability according to the New York Heart Association (NYHA) Classification. 6. Subjects with clinically significant arrhythmia or arrhythmias not stable on medical management within 2 weeks of enrollment. 7. Any abnormal liver enzyme levels (as defined ≥ULN in ALT, AST, Bilirubin and Alkaline Phosphatase levels) at time of enrollment 8. . Subjects with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, including seizure disorder. 9. History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent. 10. Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia. 11. History of venous occlusive disease (VOD), or GvHD. 12. History of stroke or intracranial hemorrhage within 6 months of enrollment. 13. 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 ≥ 3 years. 14. Clinically significant uncontrolled illness. 15. Active systemic uncontrolled infection requiring antibiotics. 16. Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection. 17. Females only: Pregnant or breastfeeding. 18. Any other condition that would, in the investigator's judgment, contraindicate the subject'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).

Inclusion Criteria

Exclusion Criteria

1. Documented informed consent of the participant and/or legally authorized representative.
2. Agreement to allow the use of archival tissue from diagnostic tumor biopsies. If unavailable, exceptions may be granted with study PI approval.
3. Age ≥ 18 years.
4. ECOG ≤ 2.
5. Life expectancy ≥ 16 weeks.
6. Histologically confirmed B-ALL or B-cell lymphoblastic lymphoma
7. Relapsed/refractory disease after failure of ≥ 2 prior lines of therapy.
8. Evidence of active BAFF-R expression at the time of enrollment.
9. Recovered to ≤ Grade 1 from the acute toxic effects (except alopecia) of prior anti-cancer therapy.
10. No known contraindications to leukapheresis, steroids or tocilizumab.
11. Ineligible for or failed prior CD19-targeted immunotherapy (e.g., blinatumomab or CD19-CAR T cells).
12. Participants with CNS involvement by leukemia (CNS2 and asymptomatic CNS3) may be considered eligible after discussions with the study team.
13. Total serum bilirubin ≤ULN (unless has Gilbert's disease, then ≤3.0)
14. AST ≤ ULN
15. ALT ≤ ULN
16. Creatinine clearance of ≥ 40 mL/min per 24-hour urine test or the Cockcroft-Gault formula
17. Left ventricular ejection fraction (LVEF) ≥ 50%
18. O2 saturation ≥ 92% on room air.
19. Seronegative for HIV Ag/Ab combo, HCV\*, and active HBV (Surface Antigen Negative)
20. 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.
21. QuantiFERON-TB Gold or equivalent\*
22. 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 3 months after the last dose of protocol therapy.
23. A complete liver evaluation (which includes ultrasound elastography, MRI of the liver and a hepatology consult) may be done if needed based on PI's recommendation.
24. Evaluation of acquired hemochromatosis (indicated through MRI of the liver and elevated levels of Ferritin) is recommended for participants who have undergone multiple transfusions and prior alloHCT.

1. Autologous/allogeneic stem cell transplant within 100 days at the time of enrollment.
2. Immunosuppressant medications within 1 months prior to protocol enrollment.
3. Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. Physiologic replacement of steroids (prednisone ≤ 7.5 mg /day or equivalent) is allowed
4. Auto-immune disease or active GVHD within 4 months prior to protocol enrollment requiring systemic immunosuppressant therapy.
5. Class III/IV cardiovascular disability according to the New York Heart Association (NYHA) Classification.
6. Subjects with clinically significant arrhythmia or arrhythmias not stable on medical management within 2 weeks of enrollment.
7. Any abnormal liver enzyme levels (as defined ≥ULN in ALT, AST, Bilirubin and Alkaline Phosphatase levels) at time of enrollment
8. . Subjects with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, including seizure disorder.
9. History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent.
10. Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia.
11. History of venous occlusive disease (VOD), or GvHD.
12. History of stroke or intracranial hemorrhage within 6 months of enrollment.
13. 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 ≥ 3 years.
14. Clinically significant uncontrolled illness.
15. Active systemic uncontrolled infection requiring antibiotics.
16. Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection.
17. Females only: Pregnant or breastfeeding.
18. Any other condition that would, in the investigator's judgment, contraindicate the subject'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

Study Contact

Hazel Cheng, PhD

CONTACT

714-599-8077

hazel.cheng@pepromenebio.com

Qing Liu-Michael, PhD

CONTACT

626-877-4603

qliumichael@coh.org

Principal Investigator

Ibrahim Aldoss, MD

PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Study Locations (Sites)

City of Hope Medical Center

Duarte, California, 91010

United States

Collaborators and Investigators

Sponsor: PeproMene Bio, Inc.

Ibrahim Aldoss, MD, 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 Date2021-05-18

Study Completion Date2027-11-18

Study Record Updates

Study Start Date2021-05-18

Study Completion Date2027-11-18

Terms related to this study

Keywords Provided by Researchers

B cell
ALL
relapsed or refractory

Additional Relevant MeSH Terms

Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia