High Risk Myelodysplastic SyndromePhase 1/2NCT03214562
Venetoclax With Combination Chemotherapy in Treating Patients With Newly Diagnosed or Relapsed or Refractory Acute Myeloid Leukemia
A Phase 1/2 study testing Cytarabine, Filgrastim and Fludarabine in people with High Risk Myelodysplastic Syndrome and Recurrent Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase Ib/II trial studies the best dose and side effects of venetoclax and how well it works when given with combination chemotherapy in treating patients with newly diagnosed acute myeloid leukemia or acute myeloid leukemia that has come back or does not respond to treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- High Risk Myelodysplastic Syndrome, Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia
- What is being tested?
- Cytarabine, Filgrastim and Fludarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 116 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Sep 2017to 30 Sep 2027
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of AML by World Health Organization (WHO) criteria. Patients with high risk myelodysplastic syndrome (MDS) as defined by the presence of >= 10% blasts are also eligible at the discretion of the principal investigator
- Patients older than 65 who are deemed fit to receive intensive chemotherapy by the treating physician will be eligible after discussion with the principal investigator (PI).
- Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
- Creatinine clearance >= 30 mL/min based on the Cockcroft-Gault equation
- Total bilirubin < 1.5 x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement
- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) < 3 x ULN unless considered due to leukemic involvement
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- Ability to understand and provide signed informed consent
- Male subjects must agree to refrain from unprotected sex and sperm donation from initial study drug administration until 90 days after the last dose of study drug
- Only patients who are relapsed, refractory, or intolerant of standard AML therapy will be eligible for Part 1 (minimum of 1 prior line of AML-directed therapy)
Who cannot join
- Patients with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (French-American-British [FAB] class M3-AML)
- Patients having received any prior BCL2 inhibitor therapy
- Subject has known active central nervous system (CNS) involvement with AML
- Patients with New York Heart Association (NYHA) class III or IV congestive heart failure or left ventricular ejection fraction (LVEF) < 40% by echocardiogram or multi-gated acquisition (MUGA) scan
- Patients with a history of myocardial infarction within the last 6 months or unstable / uncontrolled angina pectoris or history of severe and/or uncontrolled ventricular arrhythmias
- Patients with known infection with human immunodeficiency virus (HIV) or active hepatitis B or C
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- Patients with known dysphagia, short-gut syndrome, or other conditions that would affect the ingestion or gastrointestinal absorption of drugs administered orally
- Subject has any other significant medical or psychiatric history that in the opinion of the investigator would adversely affect participation in this study
- Subject has a white blood cell count > 25 x 10{9}/L. (Note: hydroxyurea is permitted to meet this criterion)
- Nursing women, women of childbearing potential (WOCBP) with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception (a) appropriate method(s) of contraception include oral or injectable hormonal birth control, intrauterine device (IUD), and double barrier methods (for example a condom in combination with a spermicide)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
M D Anderson Cancer Center
Houston, Texas, 77030
Courtney DiNardo, 713-794-1141, cdinardo@mdanderson.org
Courtney DiNardo
About this study
Official title: A Phase 1b/2 Study of the BCL-2 Inhibitor Venetoclax in Combination With Standard Intensive AML Induction/Consolidation Therapy With FLAG-IDA in Patients With Newly Diagnosed or Relapsed/Refractory AML
This phase Ib/II trial studies the best dose and side effects of venetoclax and how well it works when given with combination chemotherapy in treating patients with newly diagnosed acute myeloid leukemia or acute myeloid leukemia that has come back or does not respond to treatment. Venetoclax may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fludarabine, cytarabine, filgrastim and idarubicin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax together with combination chemotherapy may work better in treating patients with acute myeloid leukemia.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the safety and tolerability and to determine the dose-limiting toxicity and the maximum tolerated dose MTD of the combination of fludarabine, cytarabine, filgrastim (GCSF), idarubicin (FLAG-IDA) + venetoclax for patients with acute myeloid leukemia (AML) (Phase 1b).
II. To determine the overall activity of this combination in patients newly diagnosed or relapsed/refractory (AML) (Phase 2).
SECONDARY OBJECTIVES:
- Determine the preliminary assessment of efficacy by response to revised International Working Group (IWG) criteria and time to response variables including overall survival (OS), event-free survival (EFS) and duration of response (DOR).
II. Determine biomarkers that may be predictive of venetoclax activity.
OUTLINE: This is a phase I, dose-escalation study of venetoclax followed by a phase II study.
INDUCTION THERAPY: Patients receive venetoclax orally (PO) on days 1-14, fludarabine intravenously (IV) over 30 minutes on days 2-6, cytarabine IV over 4 hours on days 2-6, idarubicin IV over 15-30 minutes on days 4 and 5, filgrastim subcutaneously (SC) on days 1-7, or pegfilgrastim SC after day 5. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Patients receive venetoclax PO on days 1-7, fludarabine IV over 30 minutes on days 2-4, cytarabine IV over 4 hours on days 2-4, filgrastim SC on days 1-7, or pegfilgrastim SC after days 3. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may also receive idarubicin as in Induction Therapy during 1 cycle of Consolidation Therapy per the treating physician.
MAINTENANCE THERAPY: Patients receive venetoclax PO on days 1-28. Cycles repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up within 30 days.
- Conditions
- High Risk Myelodysplastic Syndrome, Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia
- Being tested
- Cytarabine, Filgrastim, Fludarabine, Idarubicin, Pegfilgrastim
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CytarabineDrug
Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
Given IV
FilgrastimBiological
Also called G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
Given SC
FludarabineDrug
Also called Fluradosa
Given IV
IdarubicinDrug
Also called 4-Demethoxydaunomycin, 4-Demethoxydaunorubicin, 4-DMDR
Given IV
PegfilgrastimBiological
Also called Filgrastim SD-01, filgrastim-SD/01, Fulphila, HSP-130
Given SC
VenetoclaxDrug
Also called ABT-0199, ABT-199, ABT199, GDC-0199
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (venetoclax, FLAG-IDA) | Experimental | See detailed description. Receives: Drug: Cytarabine; Biological: Filgrastim; Drug: Fludarabine; Drug: Idarubicin; Biological: Pegfilgrastim; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate (ORR)
Defined as complete response (CR) + CR with incomplete blood count recovery (CRi) + partial response (PR). Will be estimated along with the 95% credible interval.
Measured: Up to 6 years
CR/CRi rate
Will be estimated along with the 95% credible interval.
Measured: Up to 6 years
Hematologic response
Will be estimated along with the 95% credible interval.
Measured: Up to 6 years
Duration of response
Defined as the number of days from the date of initial response (PR or better) to the date of first documented disease progression/relapse or death, whichever occurs first. Will be calculated for all patients.
Measured: From the date of initial response, assessed up to 6 years
Event-free survival
Defined as the number of days from the date of treatment initiation (i.e., course 1 day 1) to the date of documented treatment failure, relapses from CR, or death from any cause, whichever occurs first. Will be calculated for all patients. Estimated using Kaplan-Meier method. Log-rank tests will be used to compare among subgroups of patients.
Measured: From the date of treatment initiation, assessed up to 6 years
Overall survival
Estimated using Kaplan-Meier method. Log-rank tests will be used to compare among subgroups of patients.
Measured: Up to 6 years
Anti-tumor activity
Will be summarized graphically and with descriptive statistics.
Measured: Up to 6 years
Pharmacodynamic markers
Two samples t-test /Wilcoxon rank sum tests will be used to compare pharmacodynamics/pharmacokinetics (PD/PK) parameters between responder and non-responders, and logistic regression analysis will also be used to evaluate the association of PD/PK parameters with response.
Measured: Up to 6 years
Drug exposure levels
Will be summarized graphically and with descriptive statistics.
Measured: Up to 6 years
Overall incidence and severity of all adverse events
Graded using Common Toxicity Criteria version 4.0. Safety data will be summarized using frequency and percentage, by category and severity.
Measured: Up to 6 years
Secondary outcomes (1)
Morphologic leukemia-free state
Will be estimated along with the 95% credible interval.
Measured: Up to 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2017
- Study start26 Sep 2017
- Primary completion30 Sep 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for High Risk Myelodysplastic SyndromeStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 116 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Courtney DiNardo, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03214562
- Sponsor's protocol ID
- 2016-0979
- Other IDs
- NCI-2018-01119, 2016-0979
- Status last verified
- Sep 2026
- First submitted
- 10 Jul 2017
- Last updated
- 18 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
DiNardo CD, Jen WY, Takahashi K, Kadia TM, Loghavi S, Daver NG, Xiao L, Reville PK, Issa GC, Short NJ, Sasaki K, Wang SA, Mullin JK, Pierce S, Bradley C, Borthakur G, Maiti A, Alvarado Y, Pemmaraju N, Ferrajoli A, Swaminathan M, Ohanian M, Abbas HA, Hammond D, Burger J, Haddad F, Montalban-Bravo G, Chien K, Masarova L, Yilmaz M, Jain N, Andreeff M, Garcia-Manero G, Kornblau S, Ravandi F, Jabbour E, Konopleva MY, Kantarjian HM. Long term results of venetoclax combined with FLAG-IDA induction and consolidation for newly diagnosed and relapsed or refractory acute myeloid leukemia. Leukemia. 2025 Apr;39(4):854-863. doi: 10.1038/s41375-025-02531-8. Epub 2025 Feb 25.
PubMed 40000842