Cladribine Venetoclax in Monocytic AML

NCT06232655 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 23-0273.cc
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Acute Myeloid Leukemia

Keywords

Relapsed; Refractory

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  Defined as the proportion of subjects who achieve a CR, CRi, or MLFS that is relapsed after or refractory to HMS/Ven

  End of Treatment, an average of 6 months

Secondary Outcomes (5)

• Adverse Events

  Duration of Treatment, an average of 6 months

• Event-free survival

  Minimum of 3 years off study

• Overall survival

  minimum of 3 years or off study

• Duration of response

  minimum of 3 years or off study

• Measurable residual disease

  Baseline through End of Treatment, an average of 6 months

Study Arms (2)

Cladribine plus Venetoclax

EXPERIMENTAL

Subjects will receive cladribine at a dose of 5mg/m2 daily via intravenous infusion on days 1 through 5 of a 28 day cycle. Concomitantly, venetoclax will be administered orally at a dose of 100mg on day 1, 200mg on day 2, and 400mg daily on days 3 through 28.

Drug: Cladribine; Drug: Venetoclax

Alternating Aza/Ven and Clad/Ven

EXPERIMENTAL

Alternating 28-day consolidation cycles of Aza/Ven (even cycles) and Clad/Ven (odd cycles), while those who do not respond will come off the study.

Drug: Cladribine; Drug: Venetoclax; Drug: Azacitidine

Interventions

Azacitidine DRUG

Medication used for the treatment of myelodysplastic syndrome, myeloid leukemia, and juvenile myelomonocytic leukemia. It is a chemical analog of cytidine, a nucleoside in DNA and RNA.. Azacitidine and its deoxy derivative, decitabine were first synthesized in Czechoslovakia as potential chemotherapeutic agents for cancer.

Also known as: Vidaza, Onureg

Alternating Aza/Ven and Clad/Ven

Cladribine DRUG

A medication used to treat hairy cell leukemia (leukemic reticuloendotheliosis) and B-cell chronic lymphocytic leukemia. Cladribine, sold under the brand name Mavenclad, is used for the treatment of adults with highly active forms of relapsing-remitting multiple sclerosis.

Also known as: Mavenclad, Leustatin

Alternating Aza/Ven and Clad/Ven; Cladribine plus Venetoclax

Venetoclax DRUG

A medication used to treat adults with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or acute myeloid leukemia (AML).

Also known as: Venclyxto

Alternating Aza/Ven and Clad/Ven; Cladribine plus Venetoclax

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A subject will be eligible for study participation if they meet the following criteria within 28 days prior to the first day of treatment. Historical records are permitted per investigator discretion.
• Subject must have confirmation of non-acute promyelocytic leukemia (APL) Acute Myeloid Leukemia (AML) with a monocytic or monoblastic phenotype or a Ras pathway mutation. The subject's AML must be relapsed after or refractory to prior treatment with hypomethylating agent (HMA) and venetoclax combination.
• Note: other prior line(s) of therapy including stem cell transplant (SCT) are allowed, but HMA/Ven must be one of the preceding treatments. Subjects who have progressed to AML after prior treatment with HMA/Ven for high grade Chronic Myelomonocytic Leukemia (CMML) or Myelodysplastic Syndrome (MDS) are also eligible.
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
• Adequate renal function as demonstrated by a calculated creatinine clearance ≥ 60 mL/min, calculated using the formula CKD-EPI Creatinine Equation (2021).
• 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
• 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).
• 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.

You may not qualify if:

• Subject has received prior treatment with cladribine for AML.
• Subject has a white blood cell count \> 25 x 109/L. Note: hydroxyurea and/or leukapheresis are permitted to meet this criterion.
• Subject has known active central nervous system (CNS) involvement of AML.
• 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.
• 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.
• Subject has a QTc interval \> 470 msec.
• 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
• Subject is pregnant or breastfeeding.
• Subject is known to be positive for HIV. HIV testing is not required.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• The Leukemia and Lymphoma Society: collaborator

Study Sites (1)

Universtiy of Colorado Hospital

Aurora, Colorado, 80045, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Interventions

Cladribine; venetoclax; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Christine McMahon, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Derek Schatz

CONTACT

720-848-0628; derek.schatz@cuanschutz.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2024
• First Posted: January 31, 2024
• Study Start: February 8, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2027
• Last Updated: December 19, 2025

Record last verified: 2025-12

Locations

US (1)