Combining eltanexor and venetoclax for treating relapsed or refractory blood cancers

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This phase I trial evaluates the safety, side effects, and optimal dosing of eltanexor in combination with venetoclax for patients with relapsed or refractory myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The study aims to determine the biologically effective dose of the combination therapy and assess its efficacy through various endpoints, including complete remission rates and overall survival. Patients will receive eltanexor orally for a specified duration alongside venetoclax, with treatment cycles repeating every 28 days. Throughout the trial, patients will undergo bone marrow biopsies and blood sample collections to monitor their response to the treatment.

Why it matters

Who can join: the full rules

Inclusion Criteria:

\- 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); 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.

Exclusion Criteria:

* 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.
* 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.

Where it's running

• Baptist Health Care Corporation
  Memphis, Tennessee, United States Recruiting
• Vanderbilt University/Ingram Cancer Center
  Nashville, Tennessee, United States Recruiting

Study contacts

• Principal investigator: Somedeb Ball, MD — Vanderbilt University/Ingram Cancer Center
• Study coordinator: Vanderbilt-Ingram Services for Timely Access
• Email: cip@vumc.org
• Phone: 800-811-8480

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Decitabine plus FLAG‑Ida chemotherapy and total‑body irradiation before donor stem cell transplant for adults with high‑risk myeloid cancers

  This test tries whether adding decitabine to FLAG‑Ida chemotherapy and total‑body irradiation before a donor stem cell transplant helps adults with high‑risk or relapsed myeloid blood cancers live longer and stay in remission.

  Recruiting Phase 1/2 Fred Hutchinson Cancer Center · Seattle, Washington · NCT06928662

• Testing a new anti-cancer drug for patients with acute myeloid leukemia and myelodysplastic syndromes

  This study is testing a new anti-cancer drug called cirtuvivint, alone and with another drug, to see if it helps people with acute myeloid leukemia and myelodysplastic syndromes feel better and live longer.

  Recruiting at 20 sites Phase 1 National Cancer Institute (NCI) · New Haven, Connecticut and 22 other locations · NCT06484062

• Using edetate calcium disodium or succimer to treat acute myeloid leukemia or myelodysplastic syndrome during chemotherapy

  This study is testing whether two drugs, edetate calcium disodium and succimer, can safely help people with acute myeloid leukemia or myelodysplastic syndrome feel better during chemotherapy.

  Recruiting Phase 1 M.D. Anderson Cancer Center · Houston, Texas · NCT03630991

• Total marrow and lymphoid irradiation with fludarabine and melphalan for older adults with refractory/relapsed AML or high-risk MDS undergoing donor stem cell transplant

  This phase 2 trial tests a targeted radiation conditioning (TMLI) with fludarabine and melphalan before a matched donor stem cell transplant in people aged 50 or older with difficult-to-treat AML or high-risk MDS.

  Recruiting Phase 2 City of Hope Medical Center · Duarte, California · NCT07582172

• Combination treatment for FLT3-mutated acute myeloid leukemia and high-risk myelodysplastic syndrome

  This study is testing a new combination of three drugs to see if it can help people with FLT3-mutated acute myeloid leukemia or high-risk myelodysplastic syndrome feel better and live longer.

  Recruiting Phase 1/2 M.D. Anderson Cancer Center · Houston, Texas · NCT05010122

• Combining decitabine/cedazuridine and venetoclax with ivosidenib or enasidenib for treating relapsed or refractory acute myeloid leukemia

  This study is testing a new combination treatment for people with relapsed or refractory acute myeloid leukemia to see if it helps them respond better to therapy.

  Recruiting Phase 1/2 M.D. Anderson Cancer Center · Houston, Texas · NCT04774393

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.