Eltanexor and Venetoclax in Relapsed or Refractory Myelodysplastic Syndrome and Acute Myeloid Leukemia

NCT06399640 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: VICC-VCHEM23008PNCI-2024-033431R01CA262287-01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial tests the safety, side effects, and best dose of eltanexor in combination with venetoclax for the treatment of patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Eltanexor works by trapping "tumor suppressing proteins" within the cell, thus causing the cancer cells to die or stop growing. 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 eltanexor together with venetoclax may be safe, tolerable and/or effective in treating patients with relapsed or refractory MDS or AML.

Conditions

Relapsed Myelodysplastic Syndrome; Refractory Myelodysplastic Syndrome; Acute Myeloid Leukemia; Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Adverse medical events will be tabulated and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.

  Up to 2 years

• Biologically effective dose (BED) of eltanexor in combination with venetoclax

  Measured by complete remission

  Up to 2 years

Secondary Outcomes (5)

• Complete remission

  Up to 2 years

• Overall response rate

  Up to 2 years

• Progression free survival

  Up to 2 years

• Overall survival

  From date on study to death for any reason, up to 2 years

• Duration of response

  From the date of first objective response until disease progression or death for any reason up to 2 years

Study Arms (1)

Eltanexor + Venetoclax

EXPERIMENTAL

Participants receive eltanexor PO QD for 5 days per week for 14, 21, or 28 days every cycle, and venetoclax PO QD on days 1-14 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants undergo bone marrow aspiration and biopsy and blood sample collection throughout the study.

Drug: Eltanexor; Drug: Venetoclax; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Biospecimen Collection

Interventions

Eltanexor DRUG

Eltanexor will be taken by mouth

Also known as: KPT-8602

Eltanexor + Venetoclax

Venetoclax DRUG

Venetoclax will be taken by mouth

Eltanexor + Venetoclax

Bone Marrow Aspiration and Biopsy PROCEDURE

Undergo bone marrow aspiration and biopsy

Eltanexor + Venetoclax

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Eltanexor + Venetoclax

Eligibility Criteria

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

You may qualify if:

• \- Age \>/= 18 years at the time of signing the Informed Consent Form (ICF); must voluntarily sign an ICF; and must be able to meet all study requirements.
• For Myelodysplastic Syndrome (MDS):
• Morphologically confirmed diagnosis of MDS with increased blasts (\>/= 5%), with a prior DNA methyltransferase inhibitor (DNMTi) treatment and progression after 2 cycles or stable disease after 4 cycles
• For Acute Myeloid Leukemia (AML):
• Morphologically confirmed diagnosis of AML in accordance with WHO diagnostic criteria that is relapsed or refractory following \>/= 1 line(s) of therapy.
• WBC must be less than 25,000/ul prior to study start (hydroxyurea allowed).
• A bone marrow aspirate must be performed, and tissue collected for entrance to the trial unless circulating blasts \>/= 5% in which case, peripheral blood can be used.
• Eastern Cooperative Oncology Group Performance Status of 0 - 2.
• Must have adequate hepatic and renal function as demonstrated by the following:
• ALT(SGPT) and/or AST (SGOT) \</= 3x upper limit of normal (ULN); Direct bilirubin \</= 1.5 x ULN; or Total bilirubin \</= 2.5x ULN (known Gilbert's Syndrome as cause of elevated bilirubin is allowed); Calculated creatinine clearance \> 50 ml/min (per the Cockroft-Gault formula).
• \- Willingness to abide by all study requirements, including contraception, maintenance of a pill diary, and acceptance of recommended supportive care medications.

You may not qualify if:

• Anticancer therapy, including investigational agents \</= 2 weeks or \</= 5 half-lives of the drug, whichever is shorter, prior to C1D1. (Use of hydroxyurea is permitted).
• Inadequate recovery from toxicity attributed to prior anti-cancer therapy to \</= Grade 1 (NCI CTCAE v5.0), excluding alopecia or fatigue.
• Prior treatment with SINE compounds or other inhibitors of XPO1.
• History of allogeneic hematopoietic stem cell transplant (HCT), or other cellular therapy product, within 3 months.
• Active acute or chronic GVHD requiring calcineurin inhibitors or steroid dosing \>/= 10mg/day or patients within 4 weeks of stopping calcineurin inhibitors for GVHD.
• Radiation therapy or major surgery within 3 weeks.
• Active, uncontrolled infection. Patients with infection under active treatment and controlled with antibiotics are eligible. Prophylaxis, even if parenteral, is acceptable.
• Inability to swallow oral medications.
• Active documented central nervous system leukemia.
• Second active malignancy within past 2 years except for basal or squamous cell carcinoma of the skin, ductal carcinoma of breast in situ or cervical carcinoma in situ.
• Women of childbearing age or potential must have negative pregnancy test and must not be actively breastfeeding to enroll on the study
• Clinically significant cardiovascular disease with major event or cardiac intervention within the past 6 months (e.g. percutaneous intervention, coronary artery bypass graft, documented cardiac heart failure) as determined by the investigator.
• Any condition not listed but deemed by the investigator to make the patient a poor candidate for clinical trial and/or treatment with investigational agents.

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• Karyopharm Therapeutics Inc: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37203, United States

RECRUITING

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Interventions

Eltanexor; venetoclax; Biopsy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Somedeb Ball, MD

  Vanderbilt University/Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vanderbilt-Ingram Services for Timely Access

CONTACT

800-811-8480; cip@vumc.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: April 30, 2024
• First Posted: May 6, 2024
• Study Start: August 14, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: March 27, 2025

Record last verified: 2025-03

Locations

US (1)