Phase 2, Open-Label, Single Arm Study, With BST-236 in Adults With R/R AML or Higher-Risk MDS
Study Details
Study Description
Brief Summary
An open label multi center study to assess the safety and efficacy of BST-236 as single agent in adult patients unfit for standard therapy with Acute Myeloid Leukemia (AML) or higher-risk (HR) Myelodysplastic Syndromes (MDS) who fail to respond or relapsed following first line therapy.
Approximately 20 adult patients with relapsed and/or refractory AML and approximately 20 adult patients with relapsed and/or refractory HR MDS, will be enrolled into the study.
Patients will be treated with 1-2 induction courses and 2-4 maintenance courses. All patients will be followed for 1 year in the study and additional 1 year post study follow-up.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: BST-236 BST-236 Intravenous, 4.5 g/m^2/d or 2.3 g/m^2/d, for 6 days |
Drug: BST-236
BST-236 is a conjugate of cytarabine and asparagine, provided as a sterile lyophilized powder for IV administration
Other Names:
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Outcome Measures
Primary Outcome Measures
- CR rate [To be assessed 5 months after the last patient was enrolled to the study]
In AML patients -The proportion of patients who achieve a CR per the IWG 2006 Criteria
- Overall response rate (ORR) [To be assessed 5 months after the last patient was enrolled to the study]
In MDS patients -Overall response rate (ORR), defined as the proportion of patients who achieve a CR or PR per proposal for modification of the International Working Group (IWG) criteria for MDS, 2006
Eligibility Criteria
Criteria
- Documented diagnosis of MDS, according to World Health Organization (WHO) classification and Revised International Prognostic Scoring System (IPSS-R) overall score ≥ 4.5 Or
Diagnosed AML according to the 2016 revision to the WHO classification of myeloid neoplasms and acute leukemia: ≥20% blasts in peripheral blood or bone marrow
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Adult ≥18 years of age
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MDS relapse following treatment with azacitidine or decitabine Or
MDS failure to achieve complete or partial response or stable disease with hematologic improvement after at least 4 cycles of azacitidine or decitabine, all within the last 1 year Or
MDS progression while on azacitidine or decitabine treatment irrespective of the number of cycles the patient has received Or
AML relapse after initial CR/CRi/CRh following treatment with: azacitidine, decitabine, Low-Dose Ara-C (LDAC) , venetoclax+HMA, or venetoclax+LDAC Or
AML failure to achieve CR, CRh or CRi following at least 4 cycles of azacitidine or decitabine or 2 cycles of venetoclax+HMA or venetoclax+LDAC within the last 1 year.
Or
AML progression while on azacitidine, decitabine, LDAC, venetoclax+HMA, venetoclax+LDAC, irrespective of the number of cycles the patient has received.
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Not able to receive an allogeneic bone marrow transplantation (BMT) at the time of study enrolment.
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Not eligible for intensive chemotherapy;
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Age ≥75 years Or
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Age ≥18 years with at least one of the following comorbidities:
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Significant heart or lung comorbidities, as reflected by at least one of the following:
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Left ventricular ejection fraction (LVEF) ≤50%
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Lung diffusing capacity for carbon monoxide (DLCO) ≤65% of expected
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Forced expiratory volume in 1 second (FEV1) ≤65% of expected
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Chronic stable angina or congestive heart failure controlled with medication
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Other comorbidity or conditions that the Investigator judges as incompatible with intensive chemotherapy, which must be documented
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ECOG=2
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Creatinine clearance (estimated by the Modification of Diet in Renal Disease (MDRD) equation or measured by 24 hours urine collection) ≥45 mL/min
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Liver enzymes (aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤2.5 times the upper limits of normal (ULN), unless attributed to leukemia (in AML patients)
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Total bilirubin ≤3 XULN unless due to Gilbert disease
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Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
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Women of reproductive potential must have a negative serum pregnancy test within 48 hours prior to the first day of any BST-236 treatment course
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Women of reproductive potential must use two forms of effective birth control methods starting from at least 1 month prior to BST-236 first dose and until 3 months following the last BST-236 administration day (acceptable methods of birth control in this study include: surgical sterilization, intrauterine devices, oral contraceptives, contraceptive patch, long-acting injectable contraceptives, or double-barrier method condom or diaphragm with spermicide)
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Male subjects must agree to refrain from unprotected sex and sperm donation from initial study drug administration until 3 months following the last dose of study drug
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Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures
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Patient must be able to adhere to the study visit schedule and other protocol requirements
Exclusion Criteria:
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MDS or AML evolving from a pre-existing myeloproliferative neoplasm (MPN)
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MDS/MPN including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (CML), juvenile myelomonocytic leukemia (JMML) and unclassifiable MDS/MPN
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Acute promyelocytic leukemia
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Previous treatment for AML or MDS with drugs other than HMA or LDAC or combinations of venetoclax with either HMA or LDAC
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Previous allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation
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Participation in a previous clinical trial involving use of an investigational drug within 30 days or at least 5 half-lives of tested drug (whichever is shorter) of study day 1
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Peripheral White Blood Cell (WBC) count >30,000 /µL in the 48 hours prior to first BST-236 dose administration. Hydroxyurea administration or leukapheresis is permitted to meet this criterion
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Administration of HMA, LDAC, or venetoclax within 14 days prior to Study Day 1
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Previous treatment with cytarabine at a dose higher than 20 mg/ m2/d
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Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment)
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Any medical or surgical condition, presence of laboratory abnormalities or psychiatric illness that may preclude safe and complete study participation based on the Investigator's judgment
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Diagnosis of malignant disease (other than AML) within the previous 12 months (excluding basal cell carcinoma of the skin without complications, "in-situ" carcinoma, or other local malignancy excised or irradiated with a high probability of cure and not treated with systemic or topical chemotherapy)
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Surgical procedure, excluding central venous catheter placement or other minor procedures (e.g. skin biopsy) in the 14 days prior to first BST-236 dose administration
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History of allergic reactions attributed to compounds of similar chemical composition as BST-236 and/or cytarabine
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Life expectancy shorter than 3 months attributed to any known medical condition other than AML/MDS
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In 12 leads ECG, corrected QT interval (QTc)>480msec or history of QT prolongation or Torsades de pointes
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ochsner LSU Health Shreveport - Academic Medical Center | Shreveport | Louisiana | United States | 71104 |
| 2 | The University of Texas MD Anderson Cancer center | Houston | Texas | United States | 77030 |
| 3 | University of Virginia Cancer Center | Charlottesville | Virginia | United States | 22903 |
| 4 | Seattle Cancer Care Alliance | Seattle | Washington | United States | 98109 |
Sponsors and Collaborators
- BioSight Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BST004