Eltanexor and Venetoclax in Relapsed or Refractory Myelodysplastic Syndrome and Acute Myeloid Leukemia
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.
Leukemia,
Myelodysplastic Syndrome,
Phase I
Phase I
Adults
Mol. targeted/Immunotherapy/Biologics
Not Available
Ball, Somedeb
National
Vanderbilt University
07-29-2024
Eligibility
18 Years and older
ALL
false
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.
\- 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):
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
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):
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.
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).
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.
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.
Eastern Cooperative Oncology Group Performance Status of 0 - 2.
Must have adequate hepatic and renal function as demonstrated by the following:
Must have adequate hepatic and renal function as demonstrated by the following:
ALT(SGPT) and/or AST (SGOT) 50 ml/min (per the Cockroft-Gault formula).
ALT(SGPT) and/or AST (SGOT) 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.
\- 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
Anticancer therapy, including investigational agents
Inadequate recovery from toxicity attributed to prior anti-cancer therapy to
Inadequate recovery from toxicity attributed to prior anti-cancer therapy to
Prior treatment with SINE compounds or other inhibitors of XPO1.
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.
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.
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.
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.
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.
Inability to swallow oral medications.
Active documented central nervous system leukemia.
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.
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
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.
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.
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.
\- 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.
\- 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):
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
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):
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.
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).
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.
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.
Eastern Cooperative Oncology Group Performance Status of 0 - 2.
Must have adequate hepatic and renal function as demonstrated by the following:
Must have adequate hepatic and renal function as demonstrated by the following:
ALT(SGPT) and/or AST (SGOT) 50 ml/min (per the Cockroft-Gault formula).
ALT(SGPT) and/or AST (SGOT) 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.
\- 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
Anticancer therapy, including investigational agents
Inadequate recovery from toxicity attributed to prior anti-cancer therapy to
Inadequate recovery from toxicity attributed to prior anti-cancer therapy to
Prior treatment with SINE compounds or other inhibitors of XPO1.
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.
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.
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.
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.
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.
Inability to swallow oral medications.
Active documented central nervous system leukemia.
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.
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
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.
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.
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.
