RecruitingPhase 1ACTRN12622000308796

Short-course treatment with venetoclax prior to non-myeloablative conditioning allogeneic stem cell transplantation for patients with haematological malignancies.

A phase 1 study to assess the safety of short-course treatment with venetoclax prior to non-myeloablative stem cell transplantation for patients with haematological malignancies.

Sponsor

Melbourne Health

Enrollment

18 participants

Start Date

Jun 8, 2022

Study Type

Interventional

Conditions

Acute leukaemia (myeloid and/or lymphoid, or biphenotypic)

Summary

The purpose of this study is to investigate the safety of oral venetoclax treatment prior to fludarabine and cyclophosphamide non-myeloablative conditioning allogeneic stem cell transplantation for patients with haematological malignancies. Who is it for? You may be eligible to join this study if you are aged 18 years or above, and have been diagnosed with with either acute leukaemia (myeloid and/or lymphoid, or biphenotypic), myelodysplastic syndrome, chronic lymphocytic leukaemia, B-cell non-Hodgkin lymphoma or plasma cell myeloma. Study details: All participants in thus study will undergo a short course of oral venetoclax between day -11 to -6 prior to fludarabine and cyclophosphamide conditioning allogeneic stem cell transplantation. The dose of venetoclax in this study will commence at 100mg daily for 5 days (total dose of 500mg), with subsequent groups increasing to a total dose of 1100mg over 5 days, 1900mg over 5 days and 2500mg over 5 days. Each participant will be assigned to received one dose level for the entire study. The safety of venetoclax treatment will be assessed by the incidence of side effects 30 days after starting the first dose of venetoclax. The study will determine the safest dose of venetoclax to be used prior to allogeneic stem cell transplantation for patients with haematological malignancies.

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Plain Language Summary

Simplified for easier understanding

For patients with blood cancers, a stem cell transplant from a matched donor (allogeneic transplant) can offer the chance of a cure — but the cancer can come back if any malignant cells survive the preparation process. Venetoclax is a targeted cancer drug that kills certain types of cancer cells and could help clear remaining disease before the transplant, potentially improving outcomes. This Phase 1 study is testing whether it is safe to give a short course of venetoclax in the days before a stem cell transplant. Participants will receive the drug at increasing doses across different groups to find the safest dose. The study is for patients with blood cancers including leukaemia, myelodysplastic syndrome, lymphoma, and myeloma. You may be eligible if you are 18 or older, have one of the listed blood cancers, are planned for an allogeneic stem cell transplant with a matched donor, and have adequate kidney and liver function. People with large lymph nodes or high tumour burden that raises the risk of tumour lysis syndrome, HIV, or certain drug interactions are not eligible.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

This is a Phase 1, single-arm, open-label, single centre, dose escalation study of short-course oral venetoclax in addition to fludarabine and cyclophosphamide conditioning prior to allogeneic stem cell transplantation (alloSCT). This study will have a 3+3 study design for dose escalation of venetoclax, followed by a dose expansion phase. Three patients will be recruited into the first dose level. If there are no dose limiting toxicities (DLTs) among these 3 patients, then recruitment into the next dose level will be permitted. If one patient develops one DLT, then a further 3 patients will be recruited into the same dose level. If fewer than 2 out of the 6 patients develop a DLT, then escalation to the next dose level will be permitted. The maximum tolerated dose (MTD) will be defined as the highest dose level at which less than 2 out of 6 patients experience a DLT. For participants receiving fludarabine and low-dose cyclophosphamide, oral venetoclax tablets are administered from day -11 to day -6, as per the dosing level described below: Dose Level A - Day -11 to -6: 100mg daily - Total dose: 600mg Dose Level B - Day -11: 100mg daily - Day -10 to -6: 200mg daily - Total dose: 1100mg Dose Level B' - Day -11: 100mg daily - Day -10: 200mg daily - Day -9 to -6: 400mg daily - Total dose: 1900mg Dose Level C - Day -11: 100mg daily - Day -10: 200mg daily - Day -9: 400mg daily - Day -8 to -6: 600mg daily - Total dose: 2500mg For participants receiving fludarabine and high-dose cyclophosphamide, oral venetoclax tablets are administered from day -14 to day -9, as per the dosing level described below: Dose Level A - Day -14 to -9: 100mg daily - Total dose: 600mg Dose Level B - Day -14: 100mg daily - Day -13 to -9: 200mg daily - Total dose: 1100mg Dose Level B' - Day -14: 100mg daily - Day -13: 200mg daily - Day -12 to -9: 400mg daily - Total dose: 1900mg Dose Level C - Day -14: 100mg daily - Day -13: 200mg daily - Day -12: 400mg daily - Day -11 to -9: 600mg daily - Total dose: 2500mg Participants will only be enrolled to one dose level as per standard 3+3 study design. Adherence to study drug will be monitored by a combination of witnessed drug administration by trial staff members and participant self-reporting.

Locations(2)

Royal Melbourne Hospital - City campus - Parkville

VIC, Australia

Peter MacCallum Cancer Centre - Melbourne

VIC, Australia

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ACTRN12622000308796