Dose Finding Study to Evaluate the Safety of BSB-2002 in Relapsed or Refractory Acute Myeloid Leukemia (AML) Patients With NPM1 Mutation

A Phase 1 Multicenter Dose Finding Study to Evaluate the Safety of BSB-2002 in Relapsed or Refractory Acute Myeloid Leukemia (AML) Patients With NPM1 Mutation

The goal of this clinical trial is to test BSB-2002 which is a new type of cellular therapy to treat blood cancer (AML). It will evaluate the safety of BSB-2002 and also determine whether it works to prevent relapse of your cancer.

Study Overview

• Status: Recruiting
• Conditions: AML, Adult Recurrent; AML - Acute Myeloid Leukemia; AML With Mutated NPM1
• Intervention / Treatment: Drug: SOC+BSB-2002; Drug: SOC+ BSB-2002

Detailed Description

This is a Phase I, multicenter, open-label, non-randomized study to characterize the safety and clinical activity of BSB-2002, a genetically modified autologous T cell product incorporating an HLA-A*02:01-restricted mutant NPM1-directed T cell receptor (TCR), administered to patients with relapsed or refractory acute myeloid leukemia (AML). Enrolled patients must be HLA-A*02:01+ and positive for the NPM1 mutation which produces the alternative amino acid sequence CLAVEEVSL (Type A, D, G or H).

The study is an adaptive dose escalation design with up to 3 cohorts to evaluate single doses of BSB-2002, employing the 3+3 design.

• Study Type: Interventional
• Enrollment (Estimated): 19
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Medical Director: Nawazish Khan, BlueSphere Bio, MD; Phone Number: 252-347-4938; Email: nkhan@bluespherebio.com

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University at St Louis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female patients, ages 18 years or older,

2. AML diagnosed per ELN criteria1 which has been treated with at least two lines of therapy,

   1. which is relapsed (after previously complete remission, CR, CRh or CRi), or
   2. refractory (failed to achieve complete remission) to the last treatment*, *Primary refractory patients should have received at least two cycles of induction treatment
3. Patients who are MRD positive by NGS for NPM1 after being MRD negative following the last treatment
4. HLA-A*02:01,
5. Positive for NPM1 mutation type A, D, G or H (see Appendix 3)2
6. Adequate venous access for apheresis or agree to use of a central line for apheresis collection,
7. Willing and able to provide informed consent and adhere to all study requirements.

Exclusion Criteria:

1. Leukemic blast count of >20,000/μl. If the blast count can be maintained below the threshold with hydroxyurea, the patient would be eligible.
2. Patients with extramedullary only AML.
3. Patients that are candidates for hematopoietic stem cell transplant.
4. Patients that are eligible to receive an approved targeted therapy.
5. Treatment with other investigational agents within 5 half-lives of the planned dosing of BSB-2002 (day 1).

6. Subject has had hematopoietic stem cell transplant (HSCT) and has any of the following:

   1. Is within 3 months of transplant;
   2. Has clinically significant graft-versus-host disease requiring systemic treatment;
   3. Has ≥ Grade 2 persistent non-hematological toxicity related to the transplant.
7. Other malignancy that requires treatment.
8. Uncontrolled bacterial, viral, or fungal infections at time of enrollment.
9. Active Hepatitis B or C infection.
10. Seropositive for Human Immunodeficiency Virus-1 or -2.
11. CNS involvement refractory to intrathecal chemotherapy and/or standard cranial- spinal radiation.
12. Subject has congestive heart failure NYHA class 3 or 4, or subject with a history of congestive heart failure NYHA class 3 or 4 in the past, unless an echocardiogram performed within 3 months prior to study entry results in a left ventricular ejection fraction that is ≥ 45%.
13. Renal insufficiency, with estimated creatinine clearance of < 40 ml/min/1.73m2 by the Cockcroft-Gault equation with adjustment if the weight is ≥ 125% of ideal body weight OR inadequate renal function defined by serum creatinine > 1.6 mg/dL
14. Total bilirubin > 2x upper limit of normal (unless attributed to Gilbert's Syndrome).
15. AST or ALT > 3x upper limit of normal.
16. Pregnant or lactating women.
17. Eastern Cooperative Oncology Group (ECOG) performance status >2.
18. Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine or systemic steroids at any dose)
19. Women of childbearing potential (WOCBP) and men who are fertile and are unwilling to use an effective birth control method or abstinence for 12 months. Effective forms of birth control are listed in the Contraception section.
20. Any condition, in the judgement of the Investigator, that would interfere with study participation, pose a significant risk to the patient, or interfere with study data interpretation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation Cohorts; AML HLA-A*02:01 and Positive for NPM1 mutation type A, D, G or H patients with an identified will be dosed in dose escalation cohorts	Drug: SOC+BSB-2002; Patients will receive BSB-2002 as a single IV infusion at day 1 following the lymphodepletion regime.
Experimental: Expansion Cohort; Once the maximum tolerated dose (MTD) or promising dose is reached additional AML HLA-A*02:01 and Positive for NPM1 mutation type A, D, G or H patients will be enrolled in the expansion cohort.	Drug: SOC+ BSB-2002; Patients will receive BSB-2002 as a single IV infusion at day 1 following the lymphodepletion regime.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with dose-limiting toxicity, adverse events (AEs) and serious AEs (SAEs)	Incidence of dose-limiting toxicity, frequency and severity of adverse events (AEs) and serious AEs (SAEs)	365 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Defined as the time from treatment to death due to any cause	Through 365 days
Number of Patients with Relapse	Presence of malignant cells in marrow (>5%), peripheral blood (>1%), or extramedullary sites by histopathology after achievement of CR, CRh or CRi any time after study treatment.	365 days
Cellular kinetics of BSB-2002 in peripheral blood	Quantitation of BSB-2002 (copies per μL of genomic DNA)	365 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Malignant Cell presence detected by Molecular MRD Methods	Presence of malignant cells in the marrow, peripheral blood, or extramedullary sites detectable only by molecular methods	365 days
Cellular kinetics of serum cytokines and biomarkers	Evaluation of inflammatory cytokines and other potential biomarkers	365 days

Collaborators and Investigators

• Sponsor: BlueSphere Bio, Inc

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: April 21, 2026
• First Submitted That Met QC Criteria: April 27, 2026
• First Posted (Actual): May 5, 2026

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: TCR; T-cell therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Leukemia, Myeloid, Acute
• Other Study ID Numbers: BSB2002-CL-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No