Using venetoclax with reduced intensity conditioning for stem cell transplantation in blood cancers
The VICTORY Study: A Phase I Study of Venetoclax in Combination With Non-myeloablative Conditioning Allogeneic Haematopoietic Stem Cell Transplantation
This study is testing if a new drug called venetoclax can be safely used with other treatments to improve outcomes for patients with blood cancers who are getting stem cell transplants.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 18 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | Melbourne Health Academic / other |
| Drugs / interventions | cyclophosphamide, fludarabine |
| Locations | 1 site (Melbourne, Victoria) |
| Trial ID | NCT05005299 on ClinicalTrials.gov |
What this trial studies
This Phase 1 clinical trial evaluates the safety and maximum tolerated dose of venetoclax when combined with fludarabine and cyclophosphamide in patients with hematological malignancies undergoing allogeneic stem cell transplantation. Participants will receive short-course venetoclax prior to a non-myeloablative conditioning regimen, followed by stem cell infusion. The study will assess dose-limiting toxicities and transplant outcomes, enrolling patients sequentially into different dose levels to determine the optimal dosing strategy.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 and older with specific hematological malignancies who are planned for allogeneic stem cell transplantation.
Not a fit: Patients with severe comorbidities or those not eligible for allogeneic stem cell transplantation may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could improve transplant outcomes and reduce complications for patients with blood cancers.
How similar studies have performed: While the combination of venetoclax with non-myeloablative conditioning is a novel approach, similar studies have shown promise in improving outcomes in hematological malignancies.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: Patients are eligible for inclusion if all of the following criteria are met: * Age ≥ 18 years * Planned to undergo alloSCT for one of the following haematological malignancies: acute leukaemia (including myeloid and/or lymphoid lineage or biphenotypic), myelodysplastic syndrome, chronic lymphocytic leukaemia (CLL), B-cell non-Hodgkin lymphoma (NHL) and plasma cell myeloma * Physician preference for a non-myeloablative conditioning regimen * Available 10/10 HLA-matched related or unrelated haematopoietic stem cell donor * Transplantation to be performed from a peripheral blood stem cell source * Adequate renal and hepatic function at screening as follows: 1. Calculated creatinine clearance \>50ml/min as measured by Cockroft Gault formula 2. AST and ALT ≤ 3.0 x ULN 3. Bilirubin ≤ 1.5 x ULN (except patients with Gilbert's Syndrome) * Able to tolerate oral medications * Disease status at the time of transplantation as follows: 1. Acute leukaemia in complete morphologic remission 2. Myelodysplastic syndrome with less than 10% bone marrow blasts 3. CLL in complete remission (CR), partial response (PR) or PR with lymphocytosis 4. NHL in CR or PR 5. Myeloma in CR, very good partial response (VGPR) or PR within 3 months of prior autologous stem cell transplantation as part of a tandem auto-allo transplant approach * ECOG performance status 0-1 Exclusion Criteria: Patients will be excluded from this study if any of the following criteria are met: * Moderate or high risk of tumour lysis syndrome prior to conditioning for allogeneic transplantation, defined as: 1. For CLL: Diameter of any lymph node or tumour mass \>5cm OR absolute lymphocyte count≥25x10\^9/L 2. For NHL: Diameter of any lymph node or tumour mass \>5cm * Prior intolerance of venetoclax or another BCL-2 inhibitor with the exception of cytopenias. Patients with prior clinical tumour lysis syndrome following venetoclax or other BCL-2 inhibitor will be excluded from the study if at the time of prior TLS their disease burden was as follows: 1. For CLL: Diameter of any lymph node or tumour mass \<5cm OR absolute lymphocyte count≤25x10\^9/L 2. For NHL: Diameter of any lymph node or tumour mass \<5cm * Reticulin fibrosis of the marrow of grade MF 2-3 * Prior allogeneic stem cell transplantation * Haemopoietic cell transplantation - comorbidity index (HCT-CI) score \> 5 * Any currently active malignancy other than the primary indication for alloSCT (except localized basal cell carcinoma or squamous cell carcinoma of the skin) * Uncontrolled systemic infection * Known malabsorption syndrome * Has received within 7 days prior to the first dose of venetoclax CYP3A4 inducers such as rifampicin, carbamazepine, phenytoin and St John's wort * Has received within 7 days prior to the first dose of venetoclax CYP3A4 inhibitors * Known positivity to HIV * Significant physical or psychiatric comorbid illness that in the investigator's opinion would impair the patient's ability to participate in the study.
Where this trial is running
Melbourne, Victoria
- Melbourne Health — Melbourne, Victoria, Australia (Recruiting)
Study contacts
- Principal investigator: David Ritchie — Melbourne Health
- Study coordinator: David Ritchie
- Email: David.Ritchie@mh.org.au
- Phone: +61393427000
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.