This website uses cookies to enhance your browsing experience, improve site performance, and gather analytics. By selecting 'Accept,' you consent to these cookies as described in our Privacy Policy.

HomeBrowseAboutFAQs
Log In
Sign Up
Acute Myeloid Leukemia
+2

Venetoclax to Improve Outcomes of Fractionated Busulfan Regimen in Patients With High-Risk AML and MDS

Sponsored by M.D. Anderson Cancer Center

About this trial

Last updated 2 years ago

Study ID

2020-0790

Status

Recruiting

Type

Interventional

Phase

Phase 2

Placebo

No

Accepting

18-75 Years
18 to 70 Years
All
All

Not accepting

Not accepting
Healthy Volunteers

Trial Timing

Ended 7 months ago

What is this trial about?

This phase II trial studies the effect of venetoclax together with busulfan, cladribine, and fludarabine in treating patients with high-risk acute myeloid leukemia or myelodysplastic syndrome who are undergoing stem cell transplant. Chemotherapy drugs, such as venetoclax, busulfan, cladribine, and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding venetoclax to the current standard of care stem cell transplant regimen of busulfan, fludarabine, and cladribine may help to control high-risk acute myeloid leukemia or myelodysplastic syndrome.

What are the participation requirements?

Yes

Inclusion Criteria

1. Age ≥ 18 and ≤ 70 years. English and non-English speaking patients are eligible.

2. Patients with acute myeloid leukemia who have previously received induction therapy and one of the following high-risk features:

1. ELN17 adverse risk prognostic group irrespective of remission status (see Appendix 2).
2. Measurable residual disease positive (MRD +)
3. Not in complete remission including complete remission without count recovery (Cri) and/or morphologic leukemia free state (MLFS), primary refractory, or relapsed disease. See Appendix 3 for details.
4. AML secondary to MDS or MPD.
5. Therapy-related AML.
6. Not in complete remission after one course of induction therapy Or Patients with myelodysplastic syndrome or CMML and one of the following high-risk features:
1. Poor or Very poor cytogenetic risk group as per IPSS-R
2. Mutated P53 or Ras pathway genes (CBL, NRAS, KRAS, NF1, PTPN1) or DNMT 3a or ASXL1 or RUNX1
3. Maximum IPSS-R >3.5 between diagnosis and the start of the preparative regimen.
4. ≥ 5% BM blasts at transplant
5. Therapy-related MDS

3. HLA-identical sibling or a minimum of 7/8 matched unrelated donor, or a haploidentical related donor available

4. Subject must voluntarily sign an informed consent

5. Female subjects of childbearing potential must have negative results for pregnancy test

6. Adequate hepatic and renal function per local laboratory reference range as follows:

- Aspartate transaminase (AST) and alanine transaminase (ALT) < 3.0X ULN
- Bilirubin <1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
- Subject must have adequate renal function as demonstrated by a creatinine clearance ≥ 50 mL/min; calculated by the Cockcroft Gault formula or measured by 24 hours urine collection.
No

Exclusion Criteria

1. Subject is known to be positive for HIV.

2. Subject has cognitive impairments and/or is a prisoner.

3. Subject has acute promyelocytic leukemia

4. Subject has known active CNS involvement with AML.

5. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:

- Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
- Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative-, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate

6. Cardiac history of CHF requiring treatment or Ejection Fraction < 50% or unstable angina;

7. Corrected DLCO < 65% or FEV1 < 65%;

8. Administration or consumption of any of the following within 3 days prior to the first dose of study drug:

- grapefruit or grapefruit products
- Seville oranges (including marmalade containing Seville oranges)
- star fruit

9. Prior gemtuzumab ozogamicin and/or inotuzumab ozogamicin use

10. Patients with cognitive impairments and/or any serious unstable pre-existing medical condition or psychiatric disorder that can interfere with safety or with obtaining informed consent or compliance with study procedures.

Locations

Location

Status

Recruiting