RECRUITING

Cladribine Venetoclax in Monocytic AML

Conditions

Acute Myeloid Leukemia Relapsed Refractory

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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

Investigation of Relapsed or refractory AML with a monocytic phenotype after failure of hypomethylating agent+venetoclax

Official Title

Study of Cladribine+Venetoclax After Failure of Venetoclax+Hypomethylating Agent in Monocytic AML

Quick Facts

Study Start:2024-02-08

Study Completion:2027-10

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06232655

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 to 100 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Subject must have confirmation of non-acute promyelocytic leukemia (APL) Acute Myeloid Leukemia (AML) by the World Health Organization (WHO) criteria with a monocytic or monoblastic phenotype or a Ras pathway mutation. 2. The subject's AML must be relapsed after or refractory to prior treatment with hypomethylating agent (HMA) and venetoclax combination. 3. Age ≥ 18 years 4. Projected life expectancy of at least 12 weeks 5. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2 6. Adequate renal function as demonstrated by a calculated creatinine clearance ≥ 60 mL/min, calculated using the formula CKD-EPI Creatinine Equation (2021). 7. Adequate liver function, as demonstrated by: * Aspartate aminotransferase (AST) ≤ 3.0 x ULN\* * Alanine aminotransferase (ALT) ≤ 3.0 x ULN\* * Total bilirubin ≤ 1.5 x ULN, unless considered to be due to leukemic organ involvement or Gilbert's syndrome\* \In subjects with Gilbert's syndrome, bilirubin needs to be ≤ 4 x ULN 8. Non-sterile male subjects must use contraceptive methods with partner(s) at least prior to beginning study drug administration and continuing up to 90 days after the last dose of study drug. Male subjects must agree to refrain from sperm donation from initial study drug administration until 90 days after the last dose of study drug. No contraception is required if male subjects are surgically sterile (vasectomy with medical assessment confirming surgical success) or if the male subject has a female partner who is postmenopausal or permanently sterile (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy). 9. Female subjects must be either: Postmenopausal: defined as age \> 60 years with no menses for 12 or more months without an alternative medical cause; OR * Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy); OR * If subject is of childbearing potential, use of contraception is required while on study treatment and for 6 months after the last dose. 10. Subject must voluntarily sign an informed consent, approved by the Institutional Research Board (IRB), prior to the initiation of any research-related screening or study procedures.	1. Subject has received prior treatment with cladribine for AML. 2. Subject has a white blood cell count \> 25 x 109/L. Note: hydroxyurea and/or leukapheresis are permitted to meet this criterion. 3. Subject has known active central nervous system (CNS) involvement of AML. 4. Subject exhibits evidence of uncontrolled systemic infection requiring therapy (viral, bacterial, or fungal). Uncontrolled is defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment. Patients on antibiotics, antivirals, or antifungals with controlled systemic symptoms will not be excluded. 5. Subject has any clinically significant condition(s) that in the opinion of the investigator would adversely affect his/her participating in this study, including but not limited to: * New York Heart Association heart failure \> class 2 * Renal, neurologic, psychiatric, endocrine, metabolic, immunologic, hepatic, cardiovascular disease, or bleeding disorder independent of leukemia. 6. Subject has a QTc interval \> 470 msec. 7. Subject has a history of other malignancies within 2 years prior to study entry, with the following exceptions: * Adequately treated in situ carcinoma of the breast or cervix * 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 * Prostate cancer not requiring therapy beyond hormonal therapy 8. Subject is pregnant or breastfeeding. 9. Subject is known to be positive for HIV. HIV testing is not required. 10. Subject is known to be positive for hepatitis B or C infection with the exception of those with an undetectable viral load. Hepatitis B or C testing is not required, and subjects with serologic evidence of prior vaccination to HBV may participate.

Inclusion Criteria

Exclusion Criteria

1. Subject must have confirmation of non-acute promyelocytic leukemia (APL) Acute Myeloid Leukemia (AML) by the World Health Organization (WHO) criteria with a monocytic or monoblastic phenotype or a Ras pathway mutation.
2. The subject's AML must be relapsed after or refractory to prior treatment with hypomethylating agent (HMA) and venetoclax combination.
3. Age ≥ 18 years
4. Projected life expectancy of at least 12 weeks
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
6. Adequate renal function as demonstrated by a calculated creatinine clearance ≥ 60 mL/min, calculated using the formula CKD-EPI Creatinine Equation (2021).
7. Adequate liver function, as demonstrated by:
* Aspartate aminotransferase (AST) ≤ 3.0 x ULN\*
* Alanine aminotransferase (ALT) ≤ 3.0 x ULN\*
* Total bilirubin ≤ 1.5 x ULN, unless considered to be due to leukemic organ involvement or Gilbert's syndrome\* \*In subjects with Gilbert's syndrome, bilirubin needs to be ≤ 4 x ULN
8. Non-sterile male subjects must use contraceptive methods with partner(s) at least prior to beginning study drug administration and continuing up to 90 days after the last dose of study drug. Male subjects must agree to refrain from sperm donation from initial study drug administration until 90 days after the last dose of study drug. No contraception is required if male subjects are surgically sterile (vasectomy with medical assessment confirming surgical success) or if the male subject has a female partner who is postmenopausal or permanently sterile (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).
9. Female subjects must be either:
* Postmenopausal: defined as age \> 60 years with no menses for 12 or more months without an alternative medical cause; OR
* Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy); OR
* If subject is of childbearing potential, use of contraception is required while on study treatment and for 6 months after the last dose.
10. Subject must voluntarily sign an informed consent, approved by the Institutional Research Board (IRB), prior to the initiation of any research-related screening or study procedures.

1. Subject has received prior treatment with cladribine for AML.
2. Subject has a white blood cell count \> 25 x 109/L. Note: hydroxyurea and/or leukapheresis are permitted to meet this criterion.
3. Subject has known active central nervous system (CNS) involvement of AML.
4. Subject exhibits evidence of uncontrolled systemic infection requiring therapy (viral, bacterial, or fungal). Uncontrolled is defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment. Patients on antibiotics, antivirals, or antifungals with controlled systemic symptoms will not be excluded.
5. Subject has any clinically significant condition(s) that in the opinion of the investigator would adversely affect his/her participating in this study, including but not limited to:
* New York Heart Association heart failure \> class 2
* Renal, neurologic, psychiatric, endocrine, metabolic, immunologic, hepatic, cardiovascular disease, or bleeding disorder independent of leukemia.
6. Subject has a QTc interval \> 470 msec.
7. Subject has a history of other malignancies within 2 years prior to study entry, with the following exceptions:
* Adequately treated in situ carcinoma of the breast or cervix
* 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
* Prostate cancer not requiring therapy beyond hormonal therapy
8. Subject is pregnant or breastfeeding.
9. Subject is known to be positive for HIV. HIV testing is not required.
10. Subject is known to be positive for hepatitis B or C infection with the exception of those with an undetectable viral load. Hepatitis B or C testing is not required, and subjects with serologic evidence of prior vaccination to HBV may participate.

Contacts and Locations

Study Contact

Derek Schatz

CONTACT

720-848-0628

derek.schatz@cuanschutz.edu

Principal Investigator

Christine McMahon, MD

PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Study Locations (Sites)

Universtiy of Colorado Hospital

Aurora, Colorado, 80045

United States

Collaborators and Investigators

Sponsor: University of Colorado, Denver

Christine McMahon, MD, PRINCIPAL_INVESTIGATOR, University of Colorado, Denver

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 Date2024-02-08

Study Completion Date2027-10

Study Record Updates

Study Start Date2024-02-08

Study Completion Date2027-10

Terms related to this study

Keywords Provided by Researchers

Relapsed
Refractory

Additional Relevant MeSH Terms

Acute Myeloid Leukemia