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Acute Myeloid LeukemiaPhase 1NCT05263284

8-Chloroadenosine in Combination With Venetoclax for the Treatment of Patients With Relapsed/Refractory Acute Myeloid Leukemia

A Phase 1 study testing 8-Chloroadenosine and Venetoclax in people with Acute Myeloid Leukemia and Recurrent Acute Myeloid Leukemia, run by City of Hope Medical Center at 1 site in United States.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record
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Trial summary

This phase I trial tests the safety, side effects, and best dose of a new 8-chloroadenosine in combination with venetoclax in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
8-Chloroadenosine and Venetoclax
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
31 Oct 2022to 25 Jan 2029
Phase
Phase 1
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Documented informed consent of the participant and/or legally authorized representative.
  • Age: >= 18 years.
  • Eastern Cooperative Oncology Group (ECOG) =< 2.
  • Life expectancy > 3 months.
  • Patients with histologically confirmed acute myeloid leukemia (AML), according to World Health Organization (WHO) criteria, with relapsed/refractory disease.
  • Patients must have any one of the following treatment history criteria:
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  • Relapsed AML
  • Failed at least 1 line of salvage therapy or
  • Untreated relapse and are not candidates for allogeneic hematopoietic stem cell transplantation (alloHCT)
  • De novo AML
  • have not achieved complete response (CR) after 2 lines of therapy or
  • refractory to frontline therapy and not eligible for alloHCT
  • AML evolving from myelodysplastic syndrome (MDS) or myeloproliferative disorder who have failed hypomethylating agents (HMA) or induction chemotherapy
  • Patients who have relapsed after allo-HCT are eligible if they are at least 3 months after HCT, do not have active graft versus host disease (GVHD) and are off immunosuppression except for maintenance dose of steroids (prednisone 10 mg/day or less).
  • Male subjects must agree to not donate sperm while taking protocol therapy through at least 90 days after the last dose.
  • White blood cell (WBC) =< 25 x 10^9/L prior to initiation of venetoclax. Cytoreduction with hydroxyurea prior to treatment and/or during cycle 1 may be required.
  • Total bilirubin =< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease).
  • Aspartate aminotransferase (AST) =< 2.5 x ULN.
  • Alanine aminotransferase (ALT) =< 2.5 x ULN.
  • Creatinine clearance of >= 50 mL/min per 24 hour urine test or the Cockcroft-Gault formula.
  • QTc =< 480 ms.
  • Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Agreement by females and males of childbearing potential* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months (females) and 3 months (males) after the last dose of protocol therapy.
  • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only).

Who cannot join

  • Current or planned use of other investigational agents, antineoplastic, biological, chemotherapy, or radiation therapy during the study treatment period, or within 2 weeks prior to day 1 of protocol therapy, with the following exception:
  • Hydroxyurea which may be continued through cycle 1.
  • Expected to undergo HCT within 120 days of enrollment.
  • Current or planned use of agents that prolong or suspected to prolong QTc.
  • Received strong or moderate CYP3A inducers or St. John's Wort within 7 days prior to day 1 of protocol therapy.
  • Received strong or moderate CYP3A inhibitors, or consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit within 3 days prior to day 1 of protocol therapy.
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  • P-glycoprotein (P-gp) inhibitors within 7 days prior to day 1 of protocol therapy.
  • Narrow therapeutic index P-gp substrates within 7 days prior to day 1 of protocol therapy.
  • Acute promyelocytic leukemia.
  • Active central nervous system (CNS) leukemia.
  • Active fungal infection or bacterial sepsis.
  • Class III/IV cardiovascular disability according to the New York Heart Association classification.
  • Participants with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of enrollment. Subjects with controlled, asymptomatic atrial fibrillation can enroll.
  • History of acute cardiovascular ischemic event, i.e., myocardial infarction or unstable angina within 6 months of enrollment.
  • History of unexplained syncope, significant histories of CAD (requiring revascularization by percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]), cardiomyopathy (ejection fraction [EF] < 50%).
  • Prior surgery or gastrointestinal dysfunction that may affect drug absorption (e.g., gastric bypass surgery, gastrectomy).
  • Unable to swallow capsules, has a partial or small bowel obstruction, or has a gastrointestinal condition resulting in a malabsorptive syndrome (e.g. small bowel resection with malabsorption).
  • Active peptic ulcer disease.
  • Other active malignancy except for localized skin cancer, bladder, prostate, breast or cervical carcinoma in situ.
  • Females only: Pregnant or breastfeeding.
  • Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures.
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: A Phase 1 Trial of 8-Chloro-Adenosine in Combination With Venetoclax in Patients With Relapsed/Refractory Acute Myeloid Leukemia

This phase I trial tests the safety, side effects, and best dose of a new 8-chloroadenosine in combination with venetoclax in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory). 8-Chloroadenosine may help block the formation of growths that may become cancer. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving 8-chloroadenosine in combination with venetoclax may help prevent the disease from coming back in patients with acute myeloid leukemia.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Evaluate the safety and tolerability of a regimen combining 8-chloro-adenosine (8-Cl-Ado) and venetoclax in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML), including type, frequency, severity, attribution, and duration of the toxicity.

II. Establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of 8-Cl-Ado when given in combination with venetoclax.

SECONDARY OBJECTIVES:

  1. Obtain preliminary estimates of the anti-leukemia activity of the 8-Cl-Ado/venetoclax regimen by assessing the overall response rate (Complete remission[CR]+ complete remission with incomplete hematologic recovery [CRi]+ partial response [PR]) and complete remission rate (CR+CRi).

II. Obtain preliminary estimates of duration of remission (DOR), overall survival (OS), and event-free survival (EFS).

III. Determine the pharmacokinetics (PK) of plasma 8-Cl-Ado and metabolites when 8-Cl-Ado is given in combination with venetoclax.

EXPLORATORY OBJECTIVES:

  1. Evaluate PK and pharmacodynamics (PD) of VEN/8-Cl-Ado combination therapy to identify biomarkers of clinical response and resistance.

II. Identify genes and pathways associated with response to VEN/8-Cl-Ado. III. Determine the metabolic consequences of VEN/8 Cl-Ado treatment on leukemia stem cells (LSCs).

OUTLINE:

Patients receive 8-Cl-Ado intravenously (IV) over 4 hours daily on days 1-5 and venetoclax orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 28 days for up to 1 year.

Being tested
8-Chloroadenosine, Venetoclax
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.

  • 8-ChloroadenosineDrug

    Also called 8-Chloro-adenosine, 8-Cl-adenosine, 8-Cl-Ado

    Given IV

  • VenetoclaxDrug

    Also called ABT-0199, ABT-199, ABT199, GDC-0199

    Given PO

Study groups in NCT05263284
Study groupRoleWhat they receive
Treatment (8-chloroadenosine, venetoclax)ExperimentalPatients receive 8-Cl-Ado IV over 4 hours daily on days 1-5 and venetoclax PO QD on days 1-28. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: 8-Chloroadenosine; Drug: Venetoclax

What is being measured

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

  1. Incidence of adverse events (AEs)

    Toxicities will be graded using the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events version 5.0.

    Measured: Up to 1 year

  2. Dose limiting toxicity (DLT)

    Toxicities will be graded using the NCI-Common Terminology Criteria for Adverse Events version 5.0. DLT will be assessed after cycle one.

    Measured: Up to 1 cycle (Each cycle is 28 days)

Secondary outcomes (4)

  1. Time to response

    Defined by European LeukemiaNet (ELN) criteria 2017 in response-evaluable participants that achieve a best response of either complete remission (CR), complete remission with incomplete hematologic recovery (CRi), or partial response (PR) at the end of study therapy. Will be estimated using the product-limit method of Kaplan and Meier.

    Measured: Up to 1 year

  2. Duration of response (DOR)

    Patients will be considered evaluable for response if they are eligible, have baseline disease assessments, and receive 2 cycles of protocol treatment, or achieve a CR/CRi after 1 cycle of protocol treatment, or progressed. Patients will have their response classified according to the European Leukemia Network (ELN) 2017 criteria. Will be estimated using the product-limit method of Kaplan and Meier.

    Measured: From the first achievement of PR, CR, or CRi to time of disease progression, assessed up to 1 year

  3. Overall survival (OS)

    Patients will be considered evaluable for response if they are eligible, have baseline disease assessments, and receive 2 cycles of protocol treatment, or achieve a CR/CRi after 1 cycle of protocol treatment, or progressed. Patients will have their response classified according to the European Leukemia Network (ELN) 2017 criteria. Will be estimated using the product-limit method of Kaplan and Meier.

    Measured: From start of protocol treatment to time of death due to any cause, or until last follow-up, assessed up to 1 year

  4. Event-free survival (EFS)

    Patients will be considered evaluable for response if they are eligible, have baseline disease assessments, and receive 2 cycles of protocol treatment, or achieve a CR/CRi after 1 cycle of protocol treatment, or progressed. Patients will have their response classified according to the European Leukemia Network (ELN) 2017 criteria. Will be estimated using the product-limit method of Kaplan and Meier.

    Measured: From start of protocol treatment to time of disease relapse/progression or death due to any cause, whichever occurs earlier; or until last follow-up, assessed up to 1 year

Timeline

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

  1. First posted2 Mar 2022
  2. Study start31 Oct 2022
  3. Primary completion25 Jan 2029 (estimated)
  4. Study completion25 Jan 2029 (estimated)

Why it stopped: Safety Issues, status is being updated per PI due to safety issues. Study is now Temporarily Closed to Accrual.

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05263284
Sponsor's protocol ID
21380
Other IDs
NCI-2022-00234, 21380, P30CA033572
Status last verified
Oct 2026
First submitted
8 Feb 2022
Last updated
20 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 8-Chloroadenosine and Venetoclax in people with Acute Myeloid Leukemia and Recurrent Acute Myeloid Leukemia, run by City of Hope Medical Center at 1 site in United States.

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 24 inclusion and 22 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: paused, as of the sponsor's last update on 20 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Incidence of adverse events (AEs) (time frame: Up to 1 year). The study lists 2 primary outcomes in all. 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 NCT05263284.

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 20 Oct 2026.

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