A Study of Cladribine, Low Dose Cytarabine, and Venetoclax in Treatment of Relapsed/Refractory or Secondary Acute Myeloid Leukemia

NCT07423104 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: UMLEU25111
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

Acute myeloid leukemia (AML) is a bone marrow cancer that is challenging to treat. It is the most common type of acute leukemia, particularly in adults. There are around 20,000 cases of acute myeloid leukemia diagnosed in the United States every year. Despite the recent significant progress in the understanding of acute myeloid leukemia leading to the development of new therapies, significant challenges remain. The initial treatment for acute myeloid leukemia involves using therapies aimed at reducing the disease burden in the bone marrow to the lowest possible level (a state known as disease remission). This is usually followed by consolidation treatment aimed at curing the disease. The initial treatment involves high intensity chemotherapy in younger adults who can tolerate these therapies and low intensity therapies for older adults or those with other medical conditions that prohibit them from receiving high intensity chemotherapy. The consolidation therapy involves either more chemotherapy or a bone marrow transplant. In the recent years, a treatment regimen consisting of two drugs; Azacytidine and Venetoclax has become the standard of care for low intensity therapy intended for older adults. Despite significant improvement in outcomes of acute myeloid leukemia in older adults after the introduction of Azacytidine/Venetoclax, yet 40% of patients who receive this treatment will either be refractory to it or relapse after an initial remission. Those whose leukemia relapses after Azacytidine/Venetoclax treatment are left with very few treatment options and have a dismal prognosis. Based on previous laboratory studies, certain subtypes of acute myeloid leukemia tend to not respond as well to Azacytidine/Venetoclax therapy and have a better chance of responding to the treatment regimen the investigators are proposing in this study. The study treatment regimen consists of 3 drugs; Cladribine, low dose Cytarabine and Venetoclax. Demonstrating efficacy of the study regimen in treatment of relapsed/refractory acute myeloid leukemia, after prior Venetoclax therapy, will provide another treatment option for those with a relapsed/refractory disease who wish to continue receiving therapy.

Conditions

Acute Myeloid Leukemia (AML)

Keywords

acute myeloblastic leukemia; acute myelocytic leukemia; relapse; acute myelogenous leukemia

Outcome Measures

Primary Outcomes (1)

• Composite complete remission

  Best response of complete remission, complete remission with incomplete hematologic recovery or morphologic leukemia-free state after 2 cycles of treatment.

  Response assessment will be done once at the end of cycle 1 and once at the end of cycle 2 (each cycle is 28 days).

Other Outcomes (1)

• Patient reported outcomes

  Once before study treatments and once at the end of cycle 2 of treatment or earlier if the participant goes off the study before the end of cycle 2 (each cycle is 28 days)

Study Arms (1)

Arm 1

EXPERIMENTAL

cladribine, low-dose cytarabine, venetoclax.

Drug: CAV

Interventions

CAV DRUG

cladribine 5 mg/m2 intravenous infusion daily on days 1-5, cytarabine 20 mg/m2 subcutaneous injection once daily on days 1-10, venetoclax 400 mg oral daily days 1-21.

Arm 1

Eligibility Criteria

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

You may qualify if:

• Participants with relapsed/refractory AML (according to European LeukemiaNet 2022 Criteria) after treatment with a Venetoclax-containing regimen.
• Participants with MDS, MPN, or MDS/MPN overlap who develop secondary AML after treatment with a Venetoclax-containing regimen.
• Prior therapy with hydroxyurea or emergency use of Cytarabine (up to 1 gm total dose) for cytoreduction is allowed.
• Prior hematopoietic stem-cell transplant (HSCT) and/or donor lymphocyte infusion (DLI) are allowed if at the time of relapse ≥ 90 days have passed from the date of the last stem cell transplant (90-day duration not required for DLI).
• Age ≥ 18 years old.
• Eastern Oncology Group (ECOG) performance status of ≤ 2
• Participants must agree to take the following reproductive precautions:
• Negative urine pregnancy test within one week prior to starting the study therapy for all women of childbearing potential.
• Participants who could become pregnant should use effective contraception during therapy and for 6 months after the last dose of study treatments. Participants with partners who could become pregnant should also use effective contraception during therapy and for 6 months after the last dose of study treatments.
• Nursing women should discontinue breastfeeding during therapy and for 10 days after the last dose of study treatments.
• Adequate organ function as follows:
• liver function (bilirubin \< 2mg/dL, AST and/or ALT \<3 x ULN). Unless liver enzyme abnormalities are suspected by the treating investigator to be due to leukemic infiltration after discussion with the principal investigator (PI).
• kidney function (creatinine \< 1.5 x ULN)
• Ability to understand the study procedures and requirements. A signed informed consent by the participant or an authorized legal representative is required.

You may not qualify if:

• Pregnant or breastfeeding women
• Uncontrolled active infections, i.e., signs of severe sepsis or hemodynamic instability
• Concurrent diagnosis with another active malignancy (indolent or adequately treated malignancies are allowed after discussion with the PI.
• Decompensated organ failure
• Documented hypersensitivity to any of the study treatments
• Participants with a diagnosis of acute promyelocytic leukemia (APL)
• Recipients of previous HSCT who have \> grade 1 graft versus host disease (GVHD) of the gastro-intestinal tract, liver, lung or skin.
• Prior therapy with purine analogues (Fludarabine, Clofarabine or Cladribine) unless it was part of a prior HSCT conditioning regimen.

Sponsors & Collaborators

• University of Rochester: lead

Related Publications (3)

• Pei S, Shelton IT, Gillen AE, Stevens BM, Gasparetto M, Wang Y, Liu L, Liu J, Brunetti TM, Engel K, Staggs S, Showers W, Sheth AI, Amaya ML, Minhajuddin M, Winters A, Patel SB, Tolison H, Krug AE, Young TN, Schowinsky J, McMahon CM, Smith CA, Pollyea DA, Jordan CT. A Novel Type of Monocytic Leukemia Stem Cell Revealed by the Clinical Use of Venetoclax-Based Therapy. Cancer Discov. 2023 Sep 6;13(9):2032-2049. doi: 10.1158/2159-8290.CD-22-1297.

  PMID: 37358260 BACKGROUND

• Kadia TM, Reville PK, Wang X, Rausch CR, Borthakur G, Pemmaraju N, Daver NG, DiNardo CD, Sasaki K, Issa GC, Ohanian M, Montalban-Bravo G, Short NJ, Jain N, Ferrajoli A, Bhalla KN, Jabbour E, Takahashi K, Malla R, Quagliato K, Kanagal-Shamanna R, Popat UR, Andreeff M, Garcia-Manero G, Konopleva MY, Ravandi F, Kantarjian HM. Phase II Study of Venetoclax Added to Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia. J Clin Oncol. 2022 Nov 20;40(33):3848-3857. doi: 10.1200/JCO.21.02823. Epub 2022 Jun 15.

  PMID: 35704787 BACKGROUND

• Steinauer N, McCullough K, Al-Kali A, Alkhateeb HB, Begna KH, Mangaonkar AA, Saliba AN, Torghabeh M, Litzow MR, Hogan WJ, Shah M, Patnaik MM, Pardanani A, Badar T, Murthy H, Foran J, Yi CA, Tefferi A, Gangat N. Cladribine plus cytarabine plus venetoclax in acute myeloid leukemia relapsed or refractory to venetoclax plus hypomethylating agent. Haematologica. 2024 Aug 1;109(8):2706-2710. doi: 10.3324/haematol.2024.284962. No abstract available.

  PMID: 38546692 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

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

Central Study Contacts

Bassil Botros, MD

CONTACT

585-275-5863; bassil_botros@urmc.rochester.edu

Wilmot Clinical Trials Office

CONTACT

585-275-5863; wcictoresearch@urmc.rochester.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Model Details: This is a phase II single-arm single-center clinical trial that will be conducted at the University of Rochester Medical Center

Study Record Dates

• First Submitted: February 6, 2026
• First Posted: February 20, 2026
• Study Start (Estimated): August 15, 2026
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2030
• Last Updated: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share