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Leukemia, Myeloid, AcutePhase 2NCT04824924

A Phase 2 Study of Venetoclax in Combination With Low-dose HHT, G-CSF, and AZA as First-line Treatment for Newly Diagnosed Elderly AML Patients Unfit for Intensive Chemotherapy

A Phase 2 study testing The combination of HHT, venetoclax, AZA, G-CSF in people with Leukemia, Myeloid, Acute, run by Shanghai Jiao Tong University School of Medicine.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Acute myeloid leukemia (AML) is a group of heterogeneous malignancies derived from hematopoietic precursors. Patients older than 65 years can hardly benefit from standard intensive chemotherapy while having a poor toxicity tolerance, leading to a dismal prognosis. Read more about this study

Who is it for?
Ages 60 years and older
Conditions the study is for
Leukemia, Myeloid, Acute
What is being tested?
The combination of HHT, venetoclax, AZA, G-CSF
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
No sites listed yet
Study dates
Mar 2021to Mar 2024
Phase
Phase 2
Are there results?
None posted in the registry

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 60 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participant must have confirmation of Acute Myeloid Leukemia (AML) by World Health Organization (WHO) criteria, previously untreated and unfit for intensive chemotherapy
  • Participant must be >= 60 years of age.
  • Participant must have a projected life expectancy of at least 12 weeks.
  • Participant must have adequate renal function as demonstrated by a creatinine >= 30 mL/min;determined via urine collection for 24-hour creatinine clearance or by the Cockcroft Gault formula
  • Participant must have adequate liver function as demonstrated by:
  • aspartate aminotransferase (AST) <= 3.0 x ULN*
  • alanine aminotransferase (ALT) <= 3.0 x ULN*
  • bilirubin <= 1.5 x ULN* * Unless considered to be due to leukemic organ involvement i. Subjects who are < 75 years of age may have a bilirubin of <= 3.0 x ULN

Who cannot join

  • Participant has history of myeloproliferative neoplasm (MPN) including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia (CML) with or without BCR-ABL1 translocation and AML with BCR-ABL1 translocation
  • Participant has acute promyelocytic leukemia
  • Participant has known active central nervous system (CNS) involvement with AML
  • Participant is known to be positive for hepatitis B or C infection
  • Participant has received anticancer therapies including chemotherapy, radiotherapy or other investigational therapy, including targeted small molecule agents within 5 half-lives prior to first dose of study drug
  • Participant has received biologic agents (e.g. monoclonal antibodies) for anti-neoplastic intent within 30 days prior to first dose of study drug
Show all 16Show fewer
  • Participant has received the following within 7 days prior to the first dose of the study drug:
  • Steroid therapy for anti-neoplastic intent;
  • Strong and Moderate CYP3A inhibitors (see Appendix A for examples)
  • Strong and Moderate CYP3A inducers (see Appendix A for examples)
  • Participant exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy
  • Participant has a serious cardiovascular, pulmonary or renal disability
  • Participant has a history of other malignancies within 2 years prior to study entry, with the exception of:
  • Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
  • Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
  • Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent; requires discussion with TA MD.

About this study

Acute myeloid leukemia (AML) is a group of heterogeneous malignancies derived from hematopoietic precursors. Patients older than 65 years can hardly benefit from standard intensive chemotherapy while having a poor toxicity tolerance, leading to a dismal prognosis. Currently, there is no satisfactory treatment modality for this high-risk patient population, which is an unmet clinical need.

Venetoclax (ABT-199/GDC-0199, VEN) is a highly selective, oral B-cell lymphoma 2 (BCL-2) inhibitor that has shown activity in BCL-2- dependent leukemia and lymphoma cell lines, and has recently exerted encouraging therapeutic effect with manageable toxicity profile in the field of treatment of AML. Promising results have emerged in the combination of venetoclax and hypomethylating agents (HMA), decitabine or azacitidin (AZA), producing complete remission (CR) plus CR with incomplete hematologic recovery (CRi) rates of 74% and 66.7%, respectively, in previously untreated elderly AML patients.

Read more

Homoharringtonine (HHT) is an alkaloid and has been used in Chinese patients with acute and chronic myeloid leukemia for more than 30 years. The add of HHT to the combination of cytarabin and aclarubicin or daunorubicin has been proved to improve CR rate and prognosis of AML patients. Moreover, HHT combined with low-dose cytarabine and granulocyte colony-stimulating factor (G-CSF) has achieved durable efficacy in AML patients, either in the first-line or salvage setting. Interestingly, HHT has potent synergistic effects with VEN through reducing the expression of BCL-XL and MCL-1 in BCL-2 related pathways as previouly reported.

This study aims at investigating the combination of HHT, VEN, AZA and G-CSF (HVAG) in the treatment of newly diagnosed elderly AML patients who are ineligible for intensive chemotherapy.

Being tested
The combination of HHT, venetoclax, AZA, G-CSF
Keywords
AML, venetoclax, combination therapy
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.

  • The combination of HHT, venetoclax, AZA, G-CSFDrug

    HVAG regimen in a 28-day cycle HHT: d1-d7 1mg/m2; VEN: d1 100mg, d2 200mg, d3-d28 400mg; AZA: d1-d7 75mg/m2; G-CSF: d1-d7 300mg

Study groups in NCT04824924
Study groupRoleWhat they receive
HVAG regimenExperimentalNot described
Receives: Drug: The combination of HHT, venetoclax, AZA, G-CSF

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of complete remission (CR)

    including Complete Remission with incomplete Platelet recovery (CRp) and Complete Remission with incomplete hematologic recovery (CRi)

    Measured: Up to 36 months

Secondary outcomes (4)

  1. Event-free survival (EFS)

    EFS is defined as the time from the date of randomization until the date of documented relapse or discontinuation of the treatment, or initiation of other anti-leukemic treatment or death from any cause, whichever occurs first

    Measured: Up to 36months

  2. Relapse-free survival

    Relapse-free survival (RFS) will be measured from time of CR to either leukemia relapse or death, whichever comes first. Leukemia relapse will be defined as bone marrow (BM) blasts 5% or higher (not attributable to regenerating BM), any circulating blasts (not attributable to regenerating BM or growth factors), or any extra-medullary blast foci as per Revised International Working Group (R-IWG) criteria.

    Measured: 36 months

  3. Overall survival(OS)

    Measured: Up to 36 months

  4. Safety and tolerability assessed by incidence and severity of adverse events

    All grade ≥ 3 toxicities according to CTCAE (Common Terminology Criteria for Adverse Events) version 5 will be tabulated

    Measured: 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Apr 2021
  2. Study startMar 2021 (estimated)
  3. Primary completionMar 2024 (estimated)
  4. Study completionMar 2024 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
100 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04824924
Sponsor's protocol ID
YangSHEN
Status last verified
Mar 2021
First submitted
28 Mar 2021
Last updated
1 Apr 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing The combination of HHT, venetoclax, AZA, G-CSF in people with Leukemia, Myeloid, Acute, run by Shanghai Jiao Tong University School of Medicine.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 1 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of complete remission (CR) (time frame: Up to 36 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04824924.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2021.

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