← Back to Search

Alkylating agents

Venetoclax with Chemotherapy for AML and MDS

Phase 1

Recruiting

Led By Jacqueline S. Garcia, MD

Research Sponsored by Jacqueline Garcia, MD

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have a prior diagnosis of high-risk MDS or high-risk AML or therapy-related MDS or high-risk chronic myelomonocytic leukemia (CMML) or MDS/MPN unclassifiable (MDS/MPN-U)

Patient must have a matched related or an 8/8 unrelated donor option for his/her allo-HCT

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 12 months

Awards & highlights

Study Summary

This trial is testing the safety of adding Venetoclax to a standard conditioning regimen for bone marrow transplantation, as well as the safety of combining Venetoclax with azacitidine or oral decitabine/cedazuridine as maintenance therapy after transplant, in order to possibly prevent disease recurrence.

Who is the study for?

Adults diagnosed with AML, MDS, CMML, or MDS/MPN who are suitable for a bone marrow transplant using reduced intensity conditioning. They must have an ECOG performance status ≤ 2 (which means they can do some activity), adequate blood counts without recent transfusions, no severe acute GVHD if on low-dose prednisone, normal liver and kidney function tests, agree to use contraception during the study and understand the consent form. Excluded are those with prior transplants, untreated brain involvement of disease, certain dietary restrictions before treatment starts (like grapefruit), malabsorption issues that affect oral drug intake, active heart disease in last 6 months or uncontrolled infections.Check my eligibility

What is being tested?

The trial is testing Venetoclax added to Fludarabine + Busulfan as pre-transplant conditioning therapy and combined with Azacitidine or Decitabine/Cedazuridine post-transplant as maintenance therapy. The aim is to see if these combinations can safely eliminate remaining leukemia cells before transplant and prevent recurrence after.See study design

What are the potential side effects?

Potential side effects include digestive problems like nausea and diarrhea; lowered blood cell counts leading to increased infection risk; fatigue; possible liver dysfunction indicated by elevated bilirubin levels; infusion-related reactions from drugs given through veins; and potential interactions affecting other medications.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I was diagnosed with a high-risk blood cancer or related condition.

Select...

I have a donor match for my bone marrow transplant.

Select...

I can take care of myself but might not be able to do heavy physical work.

Select...

I am eligible for a stem cell transplant with a less intense preparation.

Select...

I am 18 years old or older.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 12 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~12 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 12 months for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

MTD of Venetoclax with Azacitidine as Maintenance Therapy

MTD of Venetoclax with Busulfan and Fludarabine

MTD of Venetoclax with Decitabine/cedazuridine as Maintenance Therapy

Secondary outcome measures

Compare Incidences of Mortality and Survival Between Participants in Part 1, Part 2 and Part 3

Cumulative incidence of acute graft versus host disease (GVHD) and chronic GVHD following allo-HCT

Donor granulocyte chimerism percentage

+7 more

Side effects data

From 2022 Phase 3 trial • 389 Patients • NCT02005471

33%

Neutropenia

11%

Dermatitis

11%

Hypokalaemia

11%

Neutrophil count decreased

11%

Blood creatinine increased

11%

Pneumonia pseudomonal

11%

Rhinovirus infection

11%

White blood cell count decreased

11%

Pneumonia

11%

Abdominal pain

11%

Anaemia

11%

Sepsis

11%

Gastroenteritis

11%

SARS-CoV-2 test positive

11%

Electrocardiogram QT prolonged

11%

Febrile neutropenia

11%

COVID-19

11%

Supraventricular tachycardia

100%

80%

60%

40%

20%

Study treatment Arm

Bendamustine + Rituximab Crossover Substudy

Venetoclax + Rituximab Re-Treatment Substudy

Venetoclax + Rituximab Main Study

Bendamustine + Rituximab Main Study

Trial Design

1Treatment groups

Experimental Treatment

Group I: VenetoclaxExperimental Treatment5 Interventions

This study has three periods: 1) Screening 2) Treatment with venetoclax + FluBu2 chemotherapy and transplantation and 3) Post-Transplant follow up. Dose escalations begin in level I with dose cohorts and rules for escalation/de-escalation. Part 1 dose escalation will occur using a 3+3 approach. Post-transplant period includes routine follow-up. Venetoclax: 6-7 total doses based on level assigned Busulfan: given 2x daily for 4 days Fludarabine: given 1x daily for 4 days Part 2 post-transplant period includes therapy with azacitidine and venetoclax. Dose escalation will occur using a 10+10 approach. Venetoclax: 14 doses for 8-12 cycles based on level assigned Azacitidine: 5 doses for 8-12 cycles based on level assigned Part 3 post-transplant period includes therapy with oral decitabine/cedazuridine and venetoclax. Dose escalation will occur using a 10+10 approach. Venetoclax: 14 doses for 8 cycles Decitabine/cedazuridine: 3 doses for 8 cycles

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Busulfan

2008

Completed Phase 3

~1120

Azacitidine

2012

Completed Phase 3

~1440

Fludarabine

2012

Completed Phase 3

~1100

Venetoclax

2019

Completed Phase 3

~1990

0 / 5Eligibility criteria met

Find a Location

Who is running the clinical trial?

Jacqueline Garcia, MDLead Sponsor

2 Previous Clinical Trials

52 Total Patients Enrolled

National Institutes of Health (NIH)NIH

2,701 Previous Clinical Trials

7,506,776 Total Patients Enrolled

Jacqueline S. Garcia, MDPrincipal InvestigatorDana-Farber Cancer Institute

1 Previous Clinical Trials

16 Total Patients Enrolled

Media Library

Busulfan (Alkylating agents) Clinical Trial Eligibility Overview. Trial Name: NCT03613532 — Phase 1

Acute Myeloid Leukemia Research Study Groups: Venetoclax

Acute Myeloid Leukemia Clinical Trial 2023: Busulfan Highlights & Side Effects. Trial Name: NCT03613532 — Phase 1

Busulfan (Alkylating agents) 2023 Treatment Timeline for Medical Study. Trial Name: NCT03613532 — Phase 1

Frequently Asked Questions

These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

Are there any other scientific investigations into the effects of Venetoclax?

"Presently, there are 80 Phase 3 and 736 live studies for Venetoclax. While the majority of clinical trials are located in Edmonton, Alberta; globally, 15274 sites host trials related to this medication."

Answered by AI

What is the uppermost limit of participants for this experiment?

"Affirmative. The details on clinicaltrials.gov reveal that this medical trial is actively seeking participants, having first been posted October 24th 2018 and recently updated June 30th 2022. 68 patients must be enrolled from a single site for the study to commence."

Answered by AI

What conditions often necessitate the administration of Venetoclax?

"Venetoclax is commonly administered for malignant neoplasms. However, it has also been known to beneficially address neutropenia and/or thrombocytopenia, lymphoma, non-Hodgkin's anemia and other medical issues."

Answered by AI

Is enrollment currently open for participants of this research study?

"According to the information listed on clinicaltrials.gov, this study is seeking volunteers and has been since October 24th 2018. The most recent update was made June 30th 2022."

Answered by AI

Is Venetoclax a reliable and secure medicinal option for patients?

"Due to the scarcity of clinical data, Venetoclax is assigned a score of 1 on our safety scale. As this trial is in Phase I, there are limited results demonstrating its efficacy and security."

Answered by AI

Recent research and studies

Blood AdvancesJournal

Adding Venetoclax to Fludarabine/busulfan RIC Transplant for High-risk MDS and AML Is Feasible, Safe, and Active

Garcia, Jacqueline S., Haesook T. Kim, H. Moses Murdock, Corey S. Cutler, Jennifer Brock, Mahasweta Gooptu, Vincent T. Ho, et al.. 2021. “Adding Venetoclax to Fludarabine/busulfan RIC Transplant for High-risk MDS and AML Is Feasible, Safe, and Active”. Blood Advances. American Society of Hematology. doi:10.1182/bloodadvances.2021005566.

Blood AdvancesJournal

Adding Venetoclax to Fludarabine/busulfan RIC Transplant for High-risk MDS and AML Is Feasible, Safe, and Active

clinicaltrials.govStudy

Venetoclax Added to Fludarabine + Busulfan Prior to Transplant and to Maintenance Therapy for AML, MDS, and MDS/MPN

Jacqueline Garcia, MD 2018. "Venetoclax Added to Fludarabine + Busulfan Prior to Transplant and to Maintenance Therapy for AML, MDS, and MDS/MPN". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03613532.