BSB-2002 After Cyclophosphamide and Fludarabine for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia Patients With NPM1 Mutation

NCT07583303 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 25704NCI-2026-02922P30CA033572
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of BSB-2002 when given after cyclophosphamide and fludarabine and tests how well it works in treating NPM1-mutated acute myeloid leukemia (AML) that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). BSB-2002 is a type of personalized autologous T cell receptor-modified T cell therapy. T cells are infection fighting blood cells that can kill cancer cells. The T cells given in this study come from the patient and have a new gene put in them that makes them able to recognize mutated NPM1, a protein on the surface of cancer cells. These NPM1 mutated-specific T cells may help the body's immune system identify and kill NPM1-mutated AML cells. Giving chemotherapy, such as cyclophosphamide and fludarabine, before BSB-2002 helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. Giving BSB-2002 after cyclophosphamide and fludarabine may be safe, tolerable, and/or effective in treating relapsed or refractory AML in patients with NPM1 mutation.

Conditions

Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (3)

• Incidence of dose-limiting toxicity

  Dose-limiting toxicity (DLT) will be assessed using the National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Adverse events will be coded according to the Medical Dictionary for Regulatory Activities. Each adverse event will be counted once per patient. Separate tables and listings will present treatment-emergent adverse events (TEAEs), Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESI), and dose-limiting toxicities (DLT). Tables will include system organ class, high-level term, and severity grade. Listings will also include treatment interruption or discontinuation, dose level, relevant severity scales, relationship to study intervention, expectedness, onset day, duration day, action taken, outcome, sex, age, and race.

  From the start of the infusion on day 0 through day 28

• Frequency and severity of adverse events (AEs)

  AEs will be graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) scale version (v) 5.0, cytokine release syndrome (CRS) and neurotoxicity (immune effector cell associated neurotoxicity syndrome \[ICANS\]) events will be graded by the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus criteria scales for CRS and ICANS, respectively. Tables and listings will present AEs. Tables will include system organ class, high-level term, and severity grade. Listings will also include treatment interruption or discontinuation, dose level, relevant severity scales, relationship to study intervention, expectedness, onset day, duration day, action taken, outcome, sex, age, and race.

  Up to day +365

• Frequency and severity of serious AEs

  AEs will be graded by NCI CTCAE scale v 5.0, CRS and neurotoxicity (ICANS-Immune Effector Cell-Associated Neurotoxicity) events will be graded by the ASTCT Consensus criteria scales for CRS and ICANS, respectively. Tables and listings will present serious AEs. Tables will include system organ class, high-level term, and severity grade. Listings will also include treatment interruption or discontinuation, dose level, relevant severity scales, relationship to study intervention, expectedness, onset day, duration day, action taken, outcome, sex, age, and race.

  Up to day +365

Secondary Outcomes (3)

• Complete remission (CR)

  Up to day +365

• Duration of response

  From first tumor assessment at which the overall response was recorded as CR/CRi / CRi, CRh until documented relapse, or death from any cause, whichever occurred first, assessed up to 15 years

• Overall survival

  Up to 15 years

Study Arms (1)

Treatment (cyclophosphamide, fludarabine, BSB-2002)

EXPERIMENTAL

Patients undergo leukapheresis between days -45 and -21 for manufacturing of BSB-2002. Patients then receive cyclophosphamide IV and fludarabine IV on days -5 to -3 followed by BSB-2002 IV over 30 minutes on day 0 in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection as well as bone marrow aspiration and possible biopsy throughout the study. Patients also undergo echocardiography during screening.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Cyclophosphamide; Procedure: Echocardiography Test; Drug: Fludarabine; Procedure: Leukapheresis; Drug: Single Agent Therapy

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (cyclophosphamide, fludarabine, BSB-2002)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Treatment (cyclophosphamide, fludarabine, BSB-2002)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (cyclophosphamide, fludarabine, BSB-2002)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518, B-518, B518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR 138719, WR- 138719, WR-138719, WR138719

Treatment (cyclophosphamide, fludarabine, BSB-2002)

Echocardiography Test PROCEDURE

Undergo echocardiography

Also known as: EC, Echocardiography

Treatment (cyclophosphamide, fludarabine, BSB-2002)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (cyclophosphamide, fludarabine, BSB-2002)

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocyte Adsorptive Apheresis, Leukocytopheresis, Therapeutic Leukopheresis, White Blood Cell Reduction Apheresis

Treatment (cyclophosphamide, fludarabine, BSB-2002)

Single Agent Therapy DRUG

Given BSB-2002 IV

Also known as: Drug Monotherapy, Monotherapy, Single Agent Treatment, Single Drug Therapy

Treatment (cyclophosphamide, fludarabine, BSB-2002)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent of the participant
• 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, while the request for a translated full consent is processed
• Age: ≥ 18 years
• HLA-A\*02:01
• Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Adequate venous access for apheresis or agree to use of a central line for apheresis collection
• AML diagnosed per ELN criteria which has been treated with at least two lines of therapy, and meet one of these 3 criteria:
• Which is relapsed (after previously complete remission, CR, CRh or CRi), OR
• Are refractory (failed to achieve complete remission) to the last treatment
• Primary refractory patients should have received at least two cycles of induction treatment, OR
• MRD positive (at least 1% leukemic blasts in blood or bone marrow) after being MRD negative following the last treatment
• Positive for NPM1 mutation type A, D, G or H. The confirmation for NPM1 mutation must be performed by NGS within 3 months from enrollment
• If participant has had prior hematopoietic cell transplant (HCT), all 3 of the following must be met:
• More than 3 months from transplant at the time of enrollment
• No clinically significant graft-versus (vs)-host disease requiring systemic treatment

You may not qualify if:

• Leukemic blast count of \> 20,000/µl. If the blast count can be maintained below the threshold with hydroxyurea, the patient would be eligible
• Extramedullary only AML
• Central nervous system (CNS) involvement refractory to intrathecal chemotherapy and/or standard cranial- spinal radiation
• Candidates for hematopoietic cell transplant
• Eligible to receive an approved targeted therapy
• Treatment with other investigational agents within 5 half-lives of the planned dosing of BSB-2002 (day 0)
• Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine or systemic steroids at any dose)
• Unstable cardiac disease as defined by one of the following:
• Cardiac events such as myocardial infarction (MI) within the past 6 months
• NYHA (New York Heart Association) heart failure class III-IV
• Uncontrolled atrial fibrillation or hypertension
• Uncontrolled bacterial, viral, or fungal infections at time of enrollment
• Other active malignancy that requires treatment. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Females only: Pregnant or breastfeeding
• 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 or interference with study participation or data interpretation

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Specimen Handling; Biopsy; Cyclophosphamide; fludarabine; Leukapheresis; Drug Therapy

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation

Study Officials

• Ryotaro Nakamura

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2026
• First Posted: May 13, 2026
• Study Start (Estimated): December 14, 2026
• Primary Completion (Estimated): April 16, 2027
• Study Completion (Estimated): April 16, 2027
• Last Updated: May 13, 2026

Record last verified: 2026-05

Locations

US (1)