BSB-1001 for Blood Cancers

Recruiting at 7 trial locations

Overseen By Medical Director: Nawazish Khan, MD, BlueSphere Bio

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BlueSphere Bio, Inc

Must not be taking: Investigational agents, Checkpoint inhibitors

Disqualifiers: Weight > 100 kg, Other malignancy, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

38 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cellular therapy called BSB-1001 for certain blood cancers, such as AML, ALL, and MDS. Researchers aim to determine if BSB-1001 is safe and effective in preventing cancer recurrence. Individuals who have experienced relapse or resistance to other treatments and possess specific genetic markers may be suitable candidates. Participants must have a matched donor for the treatment. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you cannot have had certain treatments like CAR-T therapy within 2 years or investigational agents recently, so it's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that BSB-1001 is likely to be safe for humans?

Research shows that BSB-1001 is a promising new treatment for blood cancers like AML, ALL, and MDS. This therapy uses specially designed T cells to target cancer cells while sparing healthy ones. Although BSB-1001 remains in the early testing stages, similar treatments are usually well-tolerated.

This trial is in its early phases, meaning researchers are beginning to gather safety information, but a complete safety profile is not yet available. In these early trials, the main focus is on safety, ensuring any side effects can be managed. Researchers closely monitor participants to address any potential issues quickly.

Prospective participants will receive support from a team dedicated to their safety and to collecting important data to better understand how the treatment works. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for blood cancers like AML (acute myeloid leukemia), ALL (acute lymphoblastic leukemia), and MDS (myelodysplastic syndromes) involve chemotherapy, targeted therapy, or stem cell transplants. However, BSB-1001 is unique because it targets the HA-1 antigen, which is a specific protein found on cancer cells in certain patients. This personalized approach allows BSB-1001 to potentially attack cancer cells more precisely, reducing harm to healthy cells. Researchers are excited about BSB-1001 because it not only offers a new way to target blood cancers but also holds promise for improved efficacy and fewer side effects compared to traditional treatments.

What evidence suggests that BSB-1001 might be an effective treatment for blood cancers?

Research has shown that BSB-1001 is a promising treatment for certain blood cancers, such as acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndromes (MDS). In this trial, participants will receive BSB-1001 in different treatment arms, including dose escalation cohorts and an expansion dose cohort. Studies have found that BSB-1001 is powerful and could improve outcomes for patients, especially those receiving a stem cell transplant from a donor. This treatment aims to prevent cancer recurrence by targeting specific parts of the cancer cells. Early evidence suggests that BSB-1001 could be effective, offering hope for patients with these challenging conditions. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for patients with blood cancers like AML, ALL, or MDS who are getting a stem cell transplant from a donor that matches their tissue type. Participants should not have had previous treatments that would interfere with the study.

Inclusion Criteria

I have a high-risk blood cancer such as AML, ALL, or MDS.

Suitable for one of the approved conditioning regimens as defined in the protocol

I have a donor match for my transplant who is fully compatible.

Exclusion Criteria

My organs are not functioning well enough for the study.

I have had a stem cell transplant before.

Treatment with other investigational agents within 5 half-lives of the planned dosing of BSB-1001 (day 0)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Patients undergo myeloablative conditioning regimens including fludarabine, thiotepa, total body irradiation, or busulfan, melphalan, fludarabine

1-2 weeks

Treatment

Patients receive CD34-selected alloHSCT followed by BSB-1001 on day 0 without prophylactic immunosuppression

1 day

Follow-up

Participants are monitored for safety and effectiveness, including cellular kinetics of BSB-1001 and incidence of GVHD

365 days

Expansion Cohort (optional)

Additional AML patients may be enrolled at the recommended dose level if the maximum tolerated dose is reached

What Are the Treatments Tested in This Trial?

Interventions

• BSB-1001

Trial Overview The study tests BSB-1001, an experimental cellular therapy added to standard care (SOC), in two parts: first, finding the right dose and then seeing how well it works at preventing cancer relapse after stem cell transplants.

How Is the Trial Designed?

Group I: Dose Escalation Cohorts Experimental Treatment 1 Intervention

AML, ALL and MDS HLA-A\*02:01 and HA-1-positive (H/H or H/R) patients with an identified HLA-matched, HA-1-negative (R/R) donor will be dosed in dose escalation cohorts

Group II: BSB-1001 Expansion Dose Experimental Treatment 1 Intervention

Once the maximum tolerated dose (MTD) or promising dose is reached additional AML HLA-A\*02:01 and HA-1-positive (H/H or H/R) patients with an identified HLA-matched, HA-1-negative (R/R) donor will be enrolled in the expansion cohort.

Who Is Running the Clinical Trial?

BlueSphere Bio, Inc

Lead Sponsor

Trials

1

Recruited

40+

Published Research Related to This Trial

BB-10010, a variant of MIP-1alpha, was well-tolerated in a phase II study involving 30 breast cancer patients undergoing chemotherapy, showing no severe adverse events and a low incidence of febrile neutropenia (4%).

Patients receiving BB-10010 had significantly higher neutrophil levels after treatment compared to controls, with a notable fivefold increase in granulocyte/macrophage colony-forming cells, suggesting enhanced recovery of the bone marrow after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase-II study of BB-10010 (macrophage inflammatory protein- 1alpha) in patients with advanced breast cancer receiving 5-fluorouracil, adriamycin, and cyclophosphamide chemotherapy. Clemons, MJ., Marshall, E., Dürig, J., et al.[2021]

BS-HH-002, a modified version of homoharringtonine, shows strong antitumor activity against pancreatic cancer by completely degrading the anti-apoptosis protein MCL-1, leading to inhibited cell growth and increased cell death.

In animal studies, BS-HH-002 demonstrated a faster absorption into the bloodstream and significantly less heart toxicity compared to its predecessor, HHT, suggesting it may be a safer and more effective treatment option for solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic effects of an innovative BS-HH-002 drug on pancreatic cancer cells via induction of complete MCL-1 degradation. Wang, AM., Qiu, R., Zhang, D., et al.[2023]

In a phase 2 study involving 36 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL), dasatinib demonstrated significant efficacy, achieving major hematologic responses in 42% of patients and complete cytogenetic responses in 58%.

Dasatinib was found to be tolerable, with only 6% of patients discontinuing treatment due to toxicity, and most adverse events were manageable, indicating it is a safe and effective option for patients with Ph-positive ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 study. Ottmann, O., Dombret, H., Martinelli, G., et al.[2022]

In a study of primary large B-cell lymphoma (DLBCL), 38% of tumors expressed active Src family kinases, which are potential targets for the drug dasatinib, and this expression was linked to poorer prognostic indicators.

Sensitivity to dasatinib varied significantly among DLBCL cell lines, with resistance associated with specific signaling changes that prevented effective inhibition of BCR-mediated pathways, highlighting the complexity of treatment responses in DLBCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic implications of Src independent calcium mobilization in diffuse large B-cell lymphoma. Hollmann, CA., Tzankov, A., Martínez-Marignac, VL., et al.[2015]

In a study of 57 patients with newly diagnosed B cell-derived hematologic malignancies, the level of B cell lymphocyte stimulating factor (BLyS) was found to be significantly higher compared to healthy volunteers, indicating its potential role as a biomarker for these diseases.

After chemotherapy, BLyS levels significantly decreased, suggesting that monitoring BLyS levels could help assess treatment response and guide diagnosis and staging in patients with B cell-derived malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Abnormal Expression and Clinical Significance of B Lymphocyte Stimulating Factor in B Cell-derived Malignant Hematologic Diseases]. Han, XL., Zhang, XY., Li, JD., et al.[2018]

In a phase II study involving 18 patients with higher-risk myelodysplastic syndrome and related conditions, dasatinib (100 mg/day) showed limited efficacy, with only 3 patients responding positively and 10 experiencing disease progression.

The treatment was found to be safe, with toxicities consistent with previous reports, indicating that while dasatinib may not be highly effective for this patient group, it does not pose significant safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II pilot study of oral dasatinib in patients with higher-risk myelodysplastic syndrome (MDS) who failed conventional therapy. Duong, VH., Jaglal, MV., Zhang, L., et al.[2015]

Ibrutinib, an oral BTK inhibitor, has shown durable clinical responses in patients with chronic lymphocytic leukemia (CLL), including those with high-risk genetic abnormalities, and is also effective in mantle cell lymphoma (MCL) and Waldenström's macroglobulinemia (WM).

While generally well tolerated, ibrutinib can cause specific side effects like bleeding and atrial fibrillation, particularly in older patients, and ongoing studies are exploring its use in combination with other therapies to enhance efficacy and reduce toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Status of Bruton's Tyrosine Kinase Inhibitor Development and Use in B-Cell Malignancies. Aw, A., Brown, JR.[2021]

The small-molecule S1, a BH3 mimetic that inhibits Bcl-2, Mcl-1, and Bcl-XL, showed variable sensitivity in killing leukaemic cells, with lethal dose 50 (LD(50)) values differing significantly across five leukaemic cell lines and 41 newly diagnosed leukaemia samples.

A predictive index for S1's effectiveness was established, indicating that the ratio of phosphorylated Bcl-2 to total Bcl-2 and Mcl-1 can forecast the response to treatment, revealing a novel mechanism where phosphorylated Bcl-2 sequesters pro-apoptotic proteins, preventing their activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An antiapoptotic Bcl-2 family protein index predicts the response of leukaemic cells to the pan-Bcl-2 inhibitor S1. Zhang, Z., Liu, Y., Song, T., et al.[2021]

BH3-mimetics are a new class of drugs that can directly target and reverse the mechanisms that allow tumors to evade apoptosis, which is crucial for tumor survival and resistance to treatment.

Clinical trials have shown that BH3-mimetics have significant anti-tumor activity in certain blood cancers and may enhance the effectiveness of other cancer therapies across a wider range of malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overcoming blocks in apoptosis with BH3-mimetic therapy in haematological malignancies. Khaw, SL., Huang, DC., Roberts, AW.[2021]

A study of over 100 hematological cell line models revealed that certain mantle cell lymphoma (MCL) cell lines are highly sensitive to B cell receptor (BCR) signaling inhibitors like ibrutinib and sotrastaurin, linked to chronic activation of the classical NF-κB pathway.

In contrast, MCL cell lines that are insensitive to these inhibitors often have genetic mutations affecting the alternative NF-κB pathway, suggesting that targeting the protein kinase NIK could be a promising new treatment strategy for patients with refractory MCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological and genomic profiling identifies NF-κB-targeted treatment strategies for mantle cell lymphoma. Rahal, R., Frick, M., Romero, R., et al.[2023]

The novel Hsp90 inhibitor BJ-B11 demonstrated significant antitumor activity against human chronic myeloid leukemia K562 cells, with an IC(50) of 1.1 μM after 48 hours, indicating effective growth inhibition with minimal toxicity to normal cells.

BJ-B11 induces apoptosis through mechanisms including cell cycle arrest, degradation of key proteins like Bcr-Abl and Akt, and activation of caspases, suggesting it could be a promising treatment for chronic myeloid leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BJ-B11, a novel Hsp90 inhibitor, induces apoptosis in human chronic myeloid leukemia K562 cells through the mitochondria-dependent pathway. Ju, HQ., Wang, SX., Xiang, YF., et al.[2016]

The BNT162b2 vaccine significantly increases both antibody and T-cell responses in patients with hematological malignancies, indicating a positive immunogenic effect after two doses.

However, only 47% of these patients achieved a protective antibody level, compared to 87% of healthy controls, highlighting that many patients may not develop sufficient immunity against COVID-19 after vaccination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weak immunogenicity of SARS-CoV-2 vaccine in patients with hematologic malignancies. Malard, F., Gaugler, B., Gozlan, J., et al.[2021]

Novobiocin (NB) effectively inhibits the growth of Bcr-Abl-positive leukemia cells, such as HL-60/Bcr-Abl and K562, by inducing apoptosis through the activation of caspases and the accumulation of cytochrome c.

NB disrupts the interaction between Bcr-Abl and Hsp90, leading to decreased levels of Bcr-Abl protein and promoting its degradation, making it a potential treatment option even for imatinib-resistant leukemia cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disruption of the Bcr-Abl/Hsp90 protein complex: a possible mechanism to inhibit Bcr-Abl-positive human leukemic blasts by novobiocin. Wu, LX., Xu, JH., Zhang, KZ., et al.[2015]

SAR103168, a novel multi-targeted kinase inhibitor, was tested in a phase I trial involving 29 patients aged 18-83 with relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

The treatment showed a pharmacokinetic profile with expected adverse events for the patient population, and no specific toxicities related to SAR103168 were identified, although the study was discontinued before reaching the maximum tolerated dose due to unpredictable drug exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of SAR103168, a novel multi-kinase inhibitor, in patients with refractory/relapsed acute leukemia or high-risk myelodysplastic syndrome. Roboz, GJ., Khoury, HJ., Jabbour, E., et al.[2021]

Citations

1. bluespherebio.com bluespherebio.com/press_release/bluesphere-bio-presents-data-demonstrating-the-potential-of-lead-product-candidate-at-37th-society-for-immunotherapy-of-cancer-sitc-annual-meeting-2/

BlueSphere Bio Presents Data Demonstrating the Potential ... Data supports BSB-1001 as a potential treatment to improve outcomes for patients with acute myeloid leukemia (AML) ... AML, ALL and MDS ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06704152

BSB-1001 in Patients Undergoing HLA-Matched Allogenic ... The goal of this clinical trial is to test BSB-1001 which is a new type of cellular therapy to treat blood cancers (AML, ALL and MDS).

3. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/558995

BSB-1001 in Patients Undergoing HLA-Matched Allogenic ... The goal of this clinical trial is to test BSB-1001 which is a new type of cellular therapy to treat blood cancers (AML, ALL and MDS).

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06704152?locStr=United+States&country=United+States&aggFilters=phase%3A2+3+4%2CstudyType%3Aint+obs&start=2023-01-01_&primComp=2027-12-31_

BSB-1001 in Patients Undergoing HLA-Matched Allogenic ... This may be indicated by a specific age or the following age groups: The age groups are: Child (birth-17); Adult (18-64); Older Adult (65+) ... A ...

5. globenewswire.com globenewswire.com/news-release/2022/11/10/2553338/0/en/BlueSphere-Bio-Presents-Data-Demonstrating-the-Potential-of-Lead-Product-Candidate-at-37th-Society-for-Immunotherapy-of-Cancer-SITC-Annual-Meeting.html

BlueSphere Bio Presents Data Demonstrating the Potential of BSB-1001 is a highly potent cell therapy with the potential to be an effective in treatment for patients with AML undergoing alloSCT. BSB-1001 ...

6. synapse.patsnap.com synapse.patsnap.com/drug/3244f89dda9341ffb4e613134ffcf28b

BSB-1001 - Drug Targets, Indications, Patents BSB-1001 is an engineered TCR T cell therapy that targets the blood-restricted antigen, HA-1. BlueSphere will provide high-risk leukemia patients with a T cell ...

7. delta.larvol.com delta.larvol.com/Products/?ProductId=bfc1f270-1d91-4451-b9f7-cc9ed3383b97

BSB-1001 / BlueSphere Bio BlueSphere Bio To Partner with NMDP BioTherapies for the Company's First-In-Human TCR-based Product Candidate in Combination with Allogeneic Hematopoietic ...

8. moffitt.org moffitt.org/cancers/leukemia/treatment/clinical-trials/

Leukemia Clinical Trials - Cancers Leukemia clinical trials are designed to better detect and treat leukemia, as well as enhance patients' quality of life. Learn about Moffitt's trials here.