RECRUITING

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

Conditions

Acute Myeloid Leukemia Recurrent Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2022-12-15

Study Completion:2027-01-25

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05263284

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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. * 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).	* 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%). * 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).

Inclusion Criteria

Exclusion Criteria

* 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.
* 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).

* 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%).
* 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).

Contacts and Locations

Principal Investigator

Vinod Pullarkat

PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Study Locations (Sites)

City of Hope Medical Center

Duarte, California, 91010

United States

Collaborators and Investigators

Sponsor: City of Hope Medical Center

Vinod Pullarkat, PRINCIPAL_INVESTIGATOR, City of Hope Medical Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-12-15

Study Completion Date2027-01-25

Study Record Updates

Study Start Date2022-12-15

Study Completion Date2027-01-25

Terms related to this study

Additional Relevant MeSH Terms

Acute Myeloid Leukemia
Recurrent Acute Myeloid Leukemia
Refractory Acute Myeloid Leukemia