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New treatment option for Hematologic Malignancies
Official title Study of SLS009 (Formerly GFH009) a Potent Highly Selective CDK9 Inhibitor in Patients With Hematologic Malignancies and High-Risk Newly Diagnosed AML
ClinicalTrials.gov ID: NCT04588922
What this study is testing
What is SLS009?
SLS009 is an investigational medicine, given as an injectable medicine, being studied as a potential treatment for hematologic malignancies.
Also referred to as GFH009.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- SLS009 (formerly GFH009) is a potent and highly selective CDK9 inhibitor. In this study the safety, tolerability, and antitumor activity of single agent SLS009 are assessed in two dose escalation groups (Group 1 in patients with relapsed/refractory AML, Group 2 in patients with relapse/refractory lymphoma/CLL/SLL).
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 12 and older
You may be able to join if
- For Groups 1, 2, 3, 4 and 5: Patients eligible for inclusion must meet all of the following criteria:
- Male or female ≥ 18 years. For Group 3 Cohorts 4 and 5 only male or female ≥18 years and pediatric patients 12-18 years and ≥40 kg body mass
- Written informed consent must be obtained prior to any screening procedures
- For AML, acute promyelocytic leukemia (APL) patients are not included in the study.
- Adequate hepatic function as evidenced by meeting all the following requirements:
You likely can't join if
- For Groups 1, 2, 3, 4 and 5: Patients eligible for inclusion must not meet any of the following criteria:
- Uncontrolled medical conditions such as hypertension (systolic blood pressure \> 160 mmHg and/or diastolic blood pressure \> 100 mmHg), a history of...
- History of previous exposure to any other CDK9 inhibitors.
- Known hypersensitivity to the study drug or excipients of the preparation or any agent given in association with this study.
- Severe cardiovascular disease within 6 months of study entry, including any of the following:
- Clinically significant heart disease such as congestive heart failure requiring treatment (NYHA class III or IV), left ventricular ejection fraction...
See the full eligibility criteria
Who can join
- For Groups 1, 2, 3, 4 and 5: Patients eligible for inclusion must meet all of the following criteria:
- Male or female ≥ 18 years. For Group 3 Cohorts 4 and 5 only male or female ≥18 years and pediatric patients 12-18 years and ≥40 kg body mass
- Written informed consent must be obtained prior to any screening procedures
- For AML, acute promyelocytic leukemia (APL) patients are not included in the study.
- Adequate hepatic function as evidenced by meeting all the following requirements:
- Total bilirubin ≤ 1.5 × upper limit of normal (ULN) except for patients with Gilbert's syndrome, who are included if total bilirubin is \< 3 × ULN or if direct bilirubin is \< 1.5 × ULN.
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤2.5 × ULN. For those with hepatic metastases, AST and ALT ≤ 5 ×ULN.
- Measured or calculated (determined by the Cockcroft-Gault equation) serum creatinine clearance (CrCl) ≥ 60 mL/min (glomerular filtration rate can be alternative to CrCl) for adult patients or serum creatinine ≤ 1.5 x...
- Amylase ≤ 1.5 × ULN.
- Eastern cooperative oncology group (ECOG) performance status 0-2.
- The electrolytes and uric acid level need to be stable judged by investigators for at least 3 days before the first dose of GFH009 (Medical intervention is permitted). For AML and other leukemias:
- Peripheral WBC counts \< 50,000/µL. Cytoreduction prior to study will be allowed with hydroxyurea; hydroxyurea use will also be permitted during treatment period in patients with proliferative, progressive disease. Use...
- Recovery to grade 0-1 from adverse events related to prior anti-tumor therapy except alopecia, fatigue, \< Grade 2 sensory neuropathy and endocrinopathies controlled with hormone replacement therapy.
- For women of childbearing potential, she must consent to use highly effective methods (e.g., total abstinence, placement of an intrauterine device) of contraception during GFH009 treatment and for an additional 90 days...
- Male or female ≥ 18 years. Pediatric patients ages 12-18 and ≥40 kg body mass.
- Patients with cytological or histologically confirmed relapsed or refractory hematologic malignancies (AML, CLL/SLL and lymphoma):
- For Lymphoma, Burkitt lymphoma, lymphoblastic lymphoma, cutaneous T-Cell lymphoma and lymphoplasmacytic lymphoma (LPL)/ Waldenstrom's macroglobulinemia (WM) will be excluded.
- Patients must not be candidates for hematopoietic cell transplant (HCT) at the time of screening.
- AML (only for Group 3): Patients relapsed on or refractory to venetoclax containing regimens. Additional requirements for specific disease conditions are:
- CLL/SLL: Peripheral blood lymphocytosis (with no other cause), CLL present on BM aspirate, or enlarged lymph node (LN), liver or spleen.
- Lymphoma (Except for other leukemias): At least one measurable or evaluable lesion as defined by the Lugano (2014) response criteria. Patients must have received at least 2 prior lines of systemic therapy.
- AML, Cohort 4 (ASXL1 mutations): AML patients relapsed on and/or refractory to therapies containing venetoclax combinations and with documented ASXL1 mutation.
- AML, Cohort 5 (Other than ASXL1 Myelodysplasia related AML defining somatic mutations): AML patients relapsed on and/or refractory to therapies containing venetoclax combinations and with documented Defining somatic...
- Life expectancy ≥ 12 weeks.
- The following hematological clinical laboratory results during screening: For lymphoma, CLL/SLL patients:
- Absolute neutrophil count: for lymphoma ≥ 1,000/µL without growth factor support in the 2 weeks prior to study entry; for CLL/SLL, ANC must be ≥ 500/µL if myelosuppression is known to be due to BM involvement with...
- Hemoglobin ≥ 7.5 g/ dL without transfusion or erythropoietin treatment in the 2 weeks prior to study entry. Patients with BM involvement will not have the threshold of hemoglobin at screening.
- Platelet count ≥ 50,000/µL without transfusion or other interventions in the 2 weeks prior to study entry. For Groups 4 and 5: Patients eligible for inclusion must meet all of the following criteria:
- For Group 4: newly diagnosed AML patients who must meet 1 or more of the following 3 criteria:
- AML patients with AML MR (AML myelodysplasia related) as defined by WHO 5th Edition (The 5th edition of the World Health Organization Classification of Hematolymphoid Tumors: Myeloid and Histiocytic/Dendritic...
- AML MM (AML with myelomonocytic/ myelomonoblastic differentiation per FAB M4/M5) and/or
- Mayo 2024 HR/VHR (Mayo Genetic Risk Models for Newly Diagnosed Acute Myeloid Leukemia Treated With Venetoclax + Hypomethylating Agent. High Risk is defined as ≥2 points where points are: ELN 2022 Adverse Karyotype: 1...
- Group 5: First-line AML patients who have failed to achieve CR, CRi, or MLFS after the first 2 cycles of azacitidine/venetoclax (defined as ≥5% blasts in bone marrow or presence of circulating blasts after 2 cycles of...
- Life expectancy ≥6 weeks.
What rules you out
- For Groups 1, 2, 3, 4 and 5: Patients eligible for inclusion must not meet any of the following criteria:
- Uncontrolled medical conditions such as hypertension (systolic blood pressure \> 160 mmHg and/or diastolic blood pressure \> 100 mmHg), a history of hypertensive crisis, or a history of hypertensive encephalopathy.
- History of previous exposure to any other CDK9 inhibitors.
- Known hypersensitivity to the study drug or excipients of the preparation or any agent given in association with this study.
- Severe cardiovascular disease within 6 months of study entry, including any of the following:
- Clinically significant heart disease such as congestive heart failure requiring treatment (NYHA class III or IV), left ventricular ejection fraction (LVEF) \ 50%, the subject is eligible), or clinically significant...
- History/evidence of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft (CABG), coronary angioplasty, or stenting).
- Average QTcF ≥ 450 msec (males) or ≥ 470 msec (females) on screening ECG.
- Moderate or above regurgitation on echocardiogram
- Patients with prior treatment with cardiotoxic agents who have experienced drug induced cardiotoxicities during or after treatment, where cardiotoxic agents include but are not limited to anthracyclines (doxorubicin...
- Patients who are on systemic antibiotics are eligible to participate as long as the antibiotics are not expected to have significant DDI with GFH009 (A list of approved concomitant medications will be provided to...
- Active hepatitis B or hepatitis C virus infection. Patients with chronic HBV infection with active disease who meet the criteria for anti HBV therapy have to be on a suppressive antiviral therapy prior to enrollment...
- They have CD4+ T-cell (CD4+) counts ≥ 350 cells/uL, and
- No history of AIDS-defining opportunistic infections within the last 12 months preceding screening, and
- Are on established ART for at least four weeks and have an HIV viral load less than 400 copies/mL prior to enrollment.
- Concomitant medications that are strong CYP3A4 inhibitors or strong inducers within 7 days prior to the first dose. Avoid consumption of Seville orange (and juice), grapefruit or grapefruit juice, grapefruit hybrids...
- Stroke or intracranial hemorrhage within 6 months.
- Major surgery within 4 weeks prior to study entry.
- Pregnant or breast-feeding females.
- Prior allogeneic stem cell transplant within 6 months of study entry. Patients who received autologous HCT, if considered to be enrolled and must be \> 3 months post-transplant and meet hematologic inclusion criteria.
- Any uncontrolled intercurrent illness or condition that in the judgement of the investigator may endanger the patient.
- Medications that are known to prolong the QT interval that could not be stopped prior to study entry judged by investigator, except azole antifungal medications in AML patients. For Groups 1, 2 and 3: Patients eligible...
- For AML and other leukemias: Systemic chemotherapy or demethylating agent therapy within 7 days, or targeted therapy within 7 days or 5 half-lives whichever is shorter, or immunotherapy within 4 weeks, or CAR-T therapy...
- Patients with bulky disease (≥ 10 cm) who require cytoreductive therapy.
- Radiotherapy with wide field radiation within 28 days or radiotherapy with a limited field of radiation for palliation within 7 days of the first dose.
- Symptomatic central nervous system (CNS) metastases or primary lymphoma such as primary CNS lymphoma, leptomeningeal disease, or spinal cord compression. Patients with asymptomatic CNS metastases who are radiologically...
- Ongoing therapy with corticosteroids greater than 20 mg of prednisone or its equivalent per day. Inhaled and topical steroids are allowed.
- Patients with a baseline cardiac biomarker abnormality (CKMB/cTnI) will be excluded.
- Patients with hypereosinophilic syndrome defined as eosinophil counts in peripheral blood of ≥1,500/µ.
- Pulmonary embolism within 6 months before study entry. Patients with a history of other clinically venous or arterial thrombotic events that the investigator feels puts the patient at risk for participation in the study...
- Concurrent malignancy within 5 years (for AML patients, 2 years) prior to entry other than adequately treated cervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cell carcinoma, prostate cancer...
- For AML patients only: Given that GFH009 is a CYP3A4 substrate and the critical role of azole antifungals (commonly strong CYP3A4 inhibitors) in the treatment of patients with AML, if use of azole antifungals is...
- people with high risk of gastrointestinal hemorrhage, including but not limiting to active ulcer with fecal occult blood test ≥++; history of hematemesis or melena within 2 months prior first dose. For Groups 4 and 5...
- For patients in Group 4, no prior anti-leukemic therapy is allowed, except for ATRA if used for suspected APL, or hydroxyurea or cytarabine if used emergently for emergent cytoreduction or disease stabilization (a...
- For AML Group 4: presence of favorable risk cytogenetic markers including: NPM1-mutations (with FLT3-ITDneg, NRASwt, KRASwt, TP53wt); IDH2-mutations (with FLT3-ITDneg, NRASwt, KRASwt, TP53wt); IDH1-mutations (with...
- Patients with a history of clinically significant venous or arterial thrombotic events that the investigator feels puts the patient at risk for participation in the study (based on overall status, medical history, or...
- Concurrent malignancy within 2 years prior to entry other than adequately treated cervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cell carcinoma, prostate cancer not requiring treatment...
- Concurrent malignancy within 2 years prior to entry other than adequately treated cervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cell carcinoma, prostate cancer not requiring treatment...
- Given that GFH009 is a CYP3A4 substrate and the critical role of azole antifungals (commonly strong CYP3A4 inhibitors) in the treatment of patients with AML, if use of azole antifungals is necessary for the patients in...
The study team makes the final eligibility decision.
Where it's taking place
- Birmingham, Alabama, United States
- Goodyear, Arizona, United States
- Duarte, California, United States
- Tampa, Florida, United States
- Newnan, Georgia, United States
- Zion, Illinois, United States
- New Orleans, Louisiana, United States
- Lake Success, New York, United States
- New York, New York, United States
- Chapel Hill, North Carolina, United States
- Greenville, South Carolina, United States
- Dallas, Texas, United States
- Houston, Texas, United States
- Bengbu, Anhui, China
- Hefei, Anhui, China
- Chongqing, Chongqing Municipality, China
- Guangzhou, Guangdong, China
- Baoding, Hebei, China
- Zhengzhou, Henan, China
- Suzhou, Jiangsu, China
+ 5 more site(s).
Compensation & support
Compensation mentioned.
ClinicalTrials.gov doesn't provide a reliable structured field for payment or travel support - confirm details with the study team.
Questions & answers
Do participants get paid in this trial?
This study's listing includes signals that participants may be compensated or receive a stipend. Amounts vary and are set by the study team - confirm the details with them.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 12 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Birmingham, Alabama, United States; Goodyear, Arizona, United States; Duarte, California, United States; Tampa, Florida, United States; Newnan, Georgia, United States; Zion, Illinois, United States and 19 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.