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

NCT05263284 | Suspended Phase 1 DMC FDA Drug

• 3 other identifiers: 21380NCI-2022-00234P30CA033572
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Refractory Acute Myeloid Leukemia; Acute Myeloid Leukemia; Recurrent Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events (AEs)

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

  Up to 1 year

• 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.

  Up to 1 cycle (Each cycle is 28 days)

Secondary Outcomes (4)

• Time to response

  Up to 1 year

• Duration of response (DOR)

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

• Overall survival (OS)

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

• Event-free survival (EFS)

  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

Study Arms (1)

Treatment (8-chloroadenosine, venetoclax)

EXPERIMENTAL

Patients 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.

Drug: 8-Chloroadenosine; Drug: Venetoclax

Interventions

8-Chloroadenosine DRUG

Given IV

Also known as: 8-Chloro-adenosine, 8-Cl-adenosine, 8-Cl-Ado

Treatment (8-chloroadenosine, venetoclax)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Treatment (8-chloroadenosine, venetoclax)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.
• 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%).

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• City of Hope Medical Center: lead

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

8-chloroadenosine; beta-apocarotenoid-14',13'-dioxygenase; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Vinod Pullarkat

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2022
• First Posted: March 2, 2022
• Study Start: December 15, 2022
• Primary Completion (Estimated): January 25, 2029
• Study Completion (Estimated): January 25, 2029
• Last Updated: April 23, 2026

Record last verified: 2026-04

Locations

US (1)