Relapsed Myelodysplastic SyndromePhase 1NCT06399640
Eltanexor and Venetoclax in Relapsed or Refractory Myelodysplastic Syndrome and Acute Myeloid Leukemia
A Phase 1 study testing Eltanexor, Venetoclax and Bone Marrow Aspiration and Biopsy in people with Relapsed Myelodysplastic Syndrome and Refractory Myelodysplastic Syndrome, run by Vanderbilt-Ingram Cancer Center at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed Myelodysplastic Syndrome, Refractory Myelodysplastic Syndrome, Acute Myeloid Leukemia
- What is being tested?
- Eltanexor, Venetoclax and Bone Marrow Aspiration and Biopsy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 2 sitesUnited States
- Study dates
- 14 Aug 2024to 1 Oct 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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); Total bilirubin </= 1.5x ULN; 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.
Who cannot join
- 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.
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- 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.
- QT interval corrected by Fridericia's formula (QTcF)>470msec for both males and females on screening ECG. Patients with a bundle branch block or in-situ pacemaker must have appropriate QT interval corrections for these conditions.
- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Baptist Health Care Corporation
Memphis, Tennessee, 38138
Salil Goorha, salil.goorha@bmhcc.org
- Recruiting
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37203
Vanderbilt-Ingram Service Services for Timely Access, 800-811-8480, cip@vumc.org
Somedeb Ball, MD
About this study
Official title: Phase Ib Study of Eltanexor and Venetoclax in Relapsed or Refractory Myelodysplastic Syndrome and Acute Myeloid Leukemia
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.
Read the detailed description
Primary objective:
- To establish the safe and biologically effective dose (BED) of eltanexor in combination with venetoclax in patients with R/R MDS and/or AML
Secondary objectives:
- To estimate the complete remission (CR) rate with eltanexor and venetoclax in patients with R/R MDS and/or AML
- To assess the overall response rate (ORR) following treatment with eltanexor/venetoclax
- To assess the overall survival of patients
- To assess the progression free survival (PFS) and duration of response (DOR) in patients treated with eltanexor/venetoclax
Exploratory objectives:
- To assess differential response between MDS and AML cohorts
- To develop and evaluate a phenotypic flow-based assay to predict response to eltanexor/venetoclax
- To assess the effect of mutational changes on response to eltanexor/venetoclax
- To measure the rates of measurable residual disease with eltanexor/venetoclax
OUTLINE: This is a dose-escalation study of eltanexor in combination with venetoclax.
Patients receive eltanexor orally (PO) once per day (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. Patients undergo bone marrow aspiration and biopsy and blood sample collection throughout the study.
After completion of study treatment, patients are followed up every 3 months for up to 24 months.
- Conditions
- Relapsed Myelodysplastic Syndrome, Refractory Myelodysplastic Syndrome, Acute Myeloid Leukemia, Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia
- Being tested
- Eltanexor, Venetoclax, Bone Marrow Aspiration and Biopsy, Biospecimen Collection
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EltanexorDrug
Also called KPT-8602
Eltanexor will be taken by mouth
VenetoclaxDrug
Venetoclax will be taken by mouth
Bone Marrow Aspiration and BiopsyProcedure or surgery
Undergo bone marrow aspiration and biopsy
Biospecimen CollectionProcedure or surgery
Undergo blood sample collection
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Eltanexor; Drug: Venetoclax; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Biospecimen Collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
Adverse medical events will be tabulated and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Measured: Up to 2 years
Biologically effective dose (BED) of eltanexor in combination with venetoclax
Measured by complete remission
Measured: Up to 2 years
Secondary outcomes (5)
Complete remission
By 95% (e.g. based on standard Gaussian methods or bootstrap methods, as appropriate) confidence intervals.
Measured: Up to 2 years
Overall response rate
By 95% (e.g. based on standard Gaussian methods or bootstrap methods, as appropriate) confidence intervals.
Measured: Up to 2 years
Progression free survival
Will be estimated using the method of Kaplan and Meier accompanied by 95% (e.g. based on standard Gaussian methods or bootstrap methods, as appropriate) confidence intervals.
Measured: Up to 2 years
Overall survival
Will be estimated using the method of Kaplan and Meier accompanied by 95% (e.g. based on standard Gaussian methods or bootstrap methods, as appropriate) confidence intervals.
Measured: From date on study to death for any reason, up to 2 years
Duration of response
Will be estimated using the method of Kaplan and Meier accompanied by 95% (e.g. based on standard Gaussian methods or bootstrap methods, as appropriate) confidence intervals.
Measured: From the date of first objective response until disease progression or death for any reason up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2024
- Study start14 Aug 2024
- Primary completion1 Feb 2027 (estimated)
- Study completion1 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Relapsed Myelodysplastic SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vanderbilt-Ingram Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Karyopharm Therapeutics Inc, National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Somedeb Ball, Vanderbilt-Ingram Cancer Center
- Investigators
- Somedeb Ball, MD, Principal investigator, Vanderbilt University/Ingram Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06399640
- Sponsor's protocol ID
- VICC-VCHEM23008P
- Other IDs
- NCI-2024-03343, 1R01CA262287-01
- Status last verified
- Jun 2026
- First submitted
- 30 Apr 2024
- Last updated
- 19 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Ball S, Awan FT, Tomlinson BK, Stopczynski T, Fischer MA, Zhao Z, Fedorov K, Kishtagari A, Mohan SR, Ayers GD, Byrne MT, Savona MR. Selinexor and Venetoclax Combination in Patients With Relapsed or Refractory Acute Myeloid Leukemia. Am J Hematol. 2026 May;101(5):1019-1024. doi: 10.1002/ajh.70266. Epub 2026 Mar 8.
PubMed 41796974
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Study of Eltanexor and Venetoclax in Relapsed or Refractory Myelodysplastic Syndrome and Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT06399640
- Acronym / sponsor ID
- VICC-VCHEM23008P
- Conditions
- Relapsed Myelodysplastic Syndrome, Refractory Myelodysplastic Syndrome, Acute Myeloid Leukemia, Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Vanderbilt-Ingram Cancer CenterUniversity, hospital or other
- Collaborators
- Karyopharm Therapeutics Inc, National Cancer Institute (NCI)
- Study start
- 14 Aug 2024 (actual)
- Primary completion
- 1 Feb 2027 (estimated)
- Study completion
- 1 Oct 2027 (estimated)
- First posted
- 6 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Primary objective:
- To establish the safe and biologically effective dose (BED) of eltanexor in combination with venetoclax in patients with R/R MDS and/or AML
Secondary objectives:
- To estimate the complete remission (CR) rate with eltanexor and venetoclax in patients with R/R MDS and/or AML
- To assess the overall response rate (ORR) following treatment with eltanexor/venetoclax
- To assess the overall survival of patients
- To assess the progression free survival (PFS) and duration of response (DOR) in patients treated with eltanexor/venetoclax
Exploratory objectives:
- To assess differential response between MDS and AML cohorts
- To develop and evaluate a phenotypic flow-based assay to predict response to eltanexor/venetoclax
- To assess the effect of mutational changes on response to eltanexor/venetoclax
- To measure the rates of measurable residual disease with eltanexor/venetoclax
OUTLINE: This is a dose-escalation study of eltanexor in combination with venetoclax.
Patients receive eltanexor orally (PO) once per day (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. Patients undergo bone marrow aspiration and biopsy and blood sample collection throughout the study.
After completion of study treatment, patients are followed up every 3 months for up to 24 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eltanexor + Venetoclax | Experimental | Drug: Eltanexor, Drug: Venetoclax, Procedure: Bone Marrow Aspiration and Biopsy, Procedure: Biospecimen CollectionParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
- 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
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EltanexorAlso: KPT-8602Eltanexor will be taken by mouth | Drug | Eltanexor + Venetoclax |
| VenetoclaxVenetoclax will be taken by mouth | Drug | Eltanexor + Venetoclax |
| Bone Marrow Aspiration and BiopsyUndergo bone marrow aspiration and biopsy | Procedure or surgery | Eltanexor + Venetoclax |
| Biospecimen CollectionUndergo blood sample collection | Procedure or surgery | Eltanexor + Venetoclax |
Primary outcome
Incidence of adverse events
Time frame: Up to 2 years
Adverse medical events will be tabulated and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Biologically effective dose (BED) of eltanexor in combination with venetoclax
Time frame: Up to 2 years
Measured by complete remission
5 secondary outcomes
Complete remission
Time frame: Up to 2 years
Overall response rate
Time frame: Up to 2 years
Progression free survival
Time frame: Up to 2 years
Overall survival
Time frame: From date on study to death for any reason, up to 2 years
Duration of response
Time frame: From the date of first objective response until disease progression or death for any reason up to 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2026.
- Derived from this study: PubMed 41796974Ball S, Awan FT, Tomlinson BK, Stopczynski T, Fischer MA, Zhao Z, Fedorov K, Kishtagari A, Mohan SR, Ayers GD, Byrne MT, Savona MR. Selinexor and Venetoclax Combination in Patients With Relapsed or Refractory Acute Myeloid Leukemia. Am J Hematol. 2026 May;101(5):1019-1024. doi: 10.1002/ajh.70266. Epub 2026 Mar 8.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Somedeb Ball, MD principal investigator
Vanderbilt University/Ingram Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Eltanexor, Venetoclax and Bone Marrow Aspiration and Biopsy in people with Relapsed Myelodysplastic Syndrome and Refractory Myelodysplastic Syndrome, run by Vanderbilt-Ingram Cancer Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Vanderbilt-Ingram Services for Timely Access (800-811-8480, cip@vumc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (time frame: Up to 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06399640, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2026.