GFH009 for Blood Cancer

Recruiting at 4 trial locations

Overseen By James Dean

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Genfleet Therapeutics (Shanghai) Inc.

Must be taking: Venetoclax

Must not be taking: CYP3A4 inhibitors, QT prolongers

Disqualifiers: Bulky disease, CNS metastases, cardiovascular disease, others

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

Compensation: Varies

Number of Visits: Unknown

160 Participants Needed

Trial Summary

What is the purpose of this trial?

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). The safety, tolerability, and antitumor activity of SLS009 in combination with venetoclax and azacitidine in patient with relapsed/refractory AML who have relapsed on or are refractory to venetoclax-based regimens are being assessed in five cohorts of the expansion Group 3.

Will I have to stop taking my current medications?

The trial requires you to stop taking medications that are strong CYP3A4 inhibitors or inducers at least 7 days before starting the study. Also, medications that prolong the QT interval should be stopped unless you're an AML patient taking azole antifungal medications.

What data supports the effectiveness of the drug GFH009 for blood cancer?

Research shows that growth factors, like those potentially in GFH009, are used to help manage blood-related conditions by improving blood cell counts after chemotherapy. This suggests that GFH009 might help in similar ways for blood cancer. ^{1 2 3 4 5}

Research Team

Dragan Cicic, MD

Principal Investigator

SELLAS Life Sciences Group, Inc.

Eligibility Criteria

This trial is for adults with certain blood cancers like AML, CLL/SLL, and lymphoma that have come back or didn't respond to treatment. They must have normal levels of bilirubin (unless they have Gilbert's syndrome), liver enzymes, amylase, lipase, and stable electrolytes. Women who can get pregnant and men with partners who can get pregnant must use two effective birth control methods during the study.

Inclusion Criteria

My liver enzymes are within the required limits.

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

Amylase and lipase ≤1.5 × ULN

Exclusion Criteria

I am HIV positive.

Average QTcF ≥ 450 msec (males) or ≥ 470 msec (females) on screening ECG

Active hepatitis B or hepatitis C virus infection

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Dose levels are escalated following the Bayesian optimal interval (BOIN) design in patients with relapsed/refractory AML and CLL/SLL or lymphoma

21 to 28 days

Dose Expansion

Assessment of safety, tolerability, and antitumor activity of SLS009 in combination with venetoclax and azacitidine in patients with relapsed/refractory AML across different cohorts

approximately 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• GFH009

Trial Overview The trial tests GFH009 alone in patients with relapsed/refractory acute myeloid leukemia (AML) or lymphomas. It also tests GFH009 combined with venetoclax and azacitidine in AML patients resistant to venetoclax-based treatments. The goal is to see how safe it is and if it helps against these cancers.

Participant Groups

Group I: Group 3 Cohort 5. 30 mg BIW in pts with r/rAML with other than ASXL1 mutations Experimental Treatment 3 Interventions

SLS009 (30 mg BIW) in combination with venetoclax and azacitidine in patients with r/r AML who have relapsed or are refractory to venetoclax-based regimens and with documented Defining somatic mutations, Cytogenetic abnormalities defining acute myeloid leukemia, myelodysplasia related, other than ASXL1 mutation per WHO 5th Edition classification.

Group II: Group 3 Cohort 4. 30 mg BIW in patients with r/r AML with ASXL1 mutation. Experimental Treatment 3 Interventions

SLS009 (30 mg BIW) in combination with venetoclax and azacitidine in patients with r/r AML who have relapsed or are refractory to venetoclax-based regimens and with documented ASXL1 mutation.

Group III: Group 3 Cohort 3. 30 mg BIW in patients with r/r AML. Experimental Treatment 3 Interventions

SLS009 (30 mg BIW) in combination with venetoclax and azacitidine in patients with r/r AML who have relapsed on or are refractory to venetoclax-based regimens. US study sites only. (Cohort completed).

Group IV: Group 3 Cohort 2. 60 mg QW in patients with r/r AML. Experimental Treatment 3 Interventions

SLS009 (60 mg QW) in combination with venetoclax and azacitidine in patients with r/r AML who have relapsed on or are refractory to venetoclax-based regimens. US study sites only. (Cohort completed).

Group V: Group 3 Cohort 1. 45 mg QW in patients with r/r AML Experimental Treatment 3 Interventions

SLS009 (45 mg QW) in combination with venetoclax and azacitidine in patients with r/r AML who have relapsed on or are refractory to venetoclax-based regimens. US study sites only. (Cohort completed)

Group VI: Group 2. Dose escalation in patients with r/r CLL/SLL or lymphoma Experimental Treatment 1 Intervention

In the dose escalation part, the dose levels will be escalated following the Bayesian optimal interval (BOIN) design. China and US study sites. (Completed).

Group VII: Group 1. Dose escalation in patients with r/r AML Experimental Treatment 1 Intervention

In the dose escalation part, the dose levels will be escalated following the Bayesian optimal interval (BOIN) design. China study sites only. (Completed).

Who Is Running the Clinical Trial?

Genfleet Therapeutics (Shanghai) Inc.

Lead Sponsor

Trials

8

Recruited

890+

Zhejiang Genfleet Therapeutics Co., Ltd.

Lead Sponsor

Trials

11

Recruited

900+

Sellas Life Sciences Group

Lead Sponsor

Trials

9

Recruited

770+

Findings from Research

In a study of 18,245 older patients with non-Hodgkin lymphoma, the use of granulocyte colony-stimulating factors (G-CSFs) was associated with a modestly increased risk of developing myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), particularly with the use of filgrastim.

Specifically, patients receiving 10 or more doses of filgrastim had a significantly higher risk of MDS/AML (HR 1.67), while pegfilgrastim did not show a similar risk increase, indicating that the type of G-CSF used may influence safety outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myelodysplastic syndrome and acute myeloid leukemia after receipt of granulocyte colony-stimulating factors in older patients with non-Hodgkin lymphoma. Calip, GS., Moran, KM., Sweiss, KI., et al.[2023]

In a study involving 282 breast cancer patients undergoing dose-dense chemotherapy, primary prophylaxis with lipegfilgrastim significantly reduced the incidence of severe neutropenia (SN) to 33.3% and febrile neutropenia (FN) to just 1.1%.

The treatment was well-tolerated, with 99.3% of patients benefiting from lipegfilgrastim, and no fatal serious adverse events reported, indicating its safety and efficacy in a real-world clinical setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylaxis of Neutropenia with Lipegfilgrastim in Breast Cancer Patients with Dose-Dense Chemotherapy: Results of a Noninterventional Study on Therapeutic Routine in Germany (NADENS). Kiechle, M., Schem, C., Lüftner, D., et al.[2023]

In a pilot study involving 56 patients with higher risk myelodysplastic syndrome (MDS), the G-HA regimen combining G-CSF with low-dose chemotherapy resulted in a complete remission rate of 61%.

The treatment was well tolerated, with manageable nonhematologic toxicities and a low mortality rate of 4% within the first 4 weeks, indicating its potential as a safe option for patients unable to undergo hematopoietic cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of granulocyte colony-stimulating factor priming combined with low-dose cytarabine and homoharringtonine in higher risk myelodysplastic syndrome patients. Wang, FX., Zhang, WG., He, AL., et al.[2018]

Growth factors (GFs) have become essential in treating hematological cancers, particularly for managing bone marrow failure and cytopenias caused by the disease or its treatments, despite initial concerns about their potential to induce leukemia.

The American Society of Clinical Oncologists (ASCO) has provided guidelines to standardize the use of GFs, which are now applied in various clinical settings, including chemotherapy support, stem cell transplantation, and emerging therapies for hematological malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Growth factors in haematological cancers. Osuji, N., Pettengell, R.[2005]

In a study of 56 AML patients, including children, a high-dose cytarabine consolidation followed by G-CSF led to a disease-free survival (DFS) rate of 61% and an overall survival rate of 62% at 30 months, indicating effective treatment outcomes.

The treatment resulted in faster recovery of neutrophils and platelets compared to traditional bone marrow rescue, with a median time of 13 days for neutrophil recovery and 32 days for platelet recovery, although there was an 11% rate of treatment-related deaths.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous peripheral blood progenitor cell transplantation mobilized with high-dose cytarabine in acute myeloid leukemia in first complete remission. Pavlovsky, S., Fernández, I., Milone, G., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Myelodysplastic syndrome and acute myeloid leukemia after receipt of granulocyte colony-stimulating factors in older patients with non-Hodgkin lymphoma. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Prophylaxis of Neutropenia with Lipegfilgrastim in Breast Cancer Patients with Dose-Dense Chemotherapy: Results of a Noninterventional Study on Therapeutic Routine in Germany (NADENS). [2023]

3. England pubmed.ncbi.nlm.nih.gov

Effect of granulocyte colony-stimulating factor priming combined with low-dose cytarabine and homoharringtonine in higher risk myelodysplastic syndrome patients. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Growth factors in haematological cancers. [2005]

5. England pubmed.ncbi.nlm.nih.gov

Autologous peripheral blood progenitor cell transplantation mobilized with high-dose cytarabine in acute myeloid leukemia in first complete remission. [2019]