Diffuse Large B-cell LymphomaPhase 1NCT03955783
Venetoclax and Selinexor in Treating Patients With Relapsed or Refractory High Risk Hematologic Malignancies
A Phase 1 study testing Venetoclax and Selinexor in people with Diffuse Large B-cell Lymphoma and Acute Myeloid Leukemia, run by Sanjay Mohan at 4 sites in United States.
Trial summary
This phase Ib trial studies the toxicity and dosing of venetoclax in combination with selinexor, and how well the combination works in treatment of patients with high risk hematologic malignancies such as diffuse large B-cell lymphoma and acute myeloid leukemia that has come back (recurrent) or does not respond to… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B-cell Lymphoma, Acute Myeloid Leukemia, Non-Hodgkin's Lymphoma
- What is being tested?
- Venetoclax and Selinexor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 4 sitesUnited States
- Study dates
- 21 Jun 2019to 1 Sep 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure.
- Age ≥ 18 years
- Life expectancy > 12 weeks.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Histologically confirmed diagnosis of one of the following, in accordance with WHO diagnostic criteria:
- Escalation:
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- Diffuse Large B-cell Lymphoma (DLBCL, including primary mediastinal large B cell lymphoma, T cell rich B cell lymphoma, and high-grade B cell lymphoma NOS). Patients with Burkitt's, lymphoblastic lymphoma, follicular lymphoma, and mantle cell lymphoma are not included. OR
- Acute Myeloid Leukemia (AML)
- Expansion:
- Diffuse Large B-cell Lymphoma and acute myeloid leukemia as above.
- VEN Refractory expansion cohort (Diffuse Large B-cell Lymphoma and acute myeloid leukemia only): Patients must have previously received and failed venetoclax therapy (either monotherapy or combination) during their treatment course (i.e., patients may receive non-VEN therapy immediately prior to enrollment on this study). Treatment failure is defined as evidence of disease progression after ≥ 1 cycle (four weeks) of full-intensity venetoclax-based therapy (i.e., 28 days exclusive of ramp-up. Patients that require dose reductions due to intolerance may be considered for this cohort after discussion with the sponsor.)
- Relapsed or refractory following ≥ 1 line(s) of prior therapy
- Patients that relapse ≥ 3 months after allogeneic hematopoietic cell transplantation (HCT) are eligible.
- Female patients of childbearing potential must agree to use two methods of contraception (including one highly effective and one effective method of contraception) and have a negative serum pregnancy test at screening. Male patients must use an effective barrier method of contraception if sexually active with a female of childbearing potential. For both male and female patients, effective methods of contraception must be used throughout the study and for 3 months following the last dose of study treatment.
- For leukemia and DLBCL with known or suspected marrow involvement, patients must have at least 10-15 mL of bone marrow aspirate material obtained within 14 days of beginning treatment on this study. Patients with DLBCL must have 3-5 unstained slides, or tissue block, available for evaluation within 14 days of study enrollment in the expansion cohorts. DLBCL patients enrolled during the escalation phase must have blocks available for submission within 28 days of beginning treatment.
- CBC testing must confirm adequate marrow reserve, as demonstrated by:
- DLBCL: Hgb ≥ 10g/dL, platelets ≥ 75,000 cells/mm3 , ANC ≥ 1,000 cells/mm3
- Adequate organ function, as demonstrated by:
- Total bilirubin < 1.5 x upper limit of normal (ULN) (except patients with Gilbert's syndrome (hereditary indirect hyperbilirubinemia), who must have a total bilirubin of < 3 x ULN, and
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal to < 2 x ULN
- Calculated creatinine clearance > 50 mL/min (per the Cockcroft-Gault formula).
- Patients with laboratory evidence of liver or kidney dysfunction secondary to underlying disease, that is expected to reverse with treatment, may be enrolled after discussion with the sponsor/investigator.
Who cannot join
- Patients who are pregnant or lactating
- Patients who received any systemic anticancer therapy including investigational agents or radiation ≤3 weeks (or ≤5 half-lives of the drug [whichever is shorter]) prior to C1D1. Hydroxyurea is permitted for up to 14 days in AML patients
- Inadequate recovery from toxicity attributed to prior anti-cancer therapy. With the exception of alopecia or fatigue, patients must have recovered to baseline or ≤ Grade 1 (NCI-CTCAE v4.03) residual toxicity prior to first dose of protocol-indicated treatment.
- Participation in another clinical trial with any investigational drug within 14 days prior to study enrollment.
- Patients included in the VEN refractory cohort that have discontinued venetoclax therapy (either monotherapy or combination) due to toxicity or hypersensitivity, including prior history of grade 3/4 TLS during prior VEN exposure
- In dose expansion cohorts, except venetoclax refractory cohort, no prior treatment with SINE compounds, another XPO1 inhibitor, or BCL-2 inhibitors.
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- Active GVHD requiring calcineurin inhibitors or steroid dosing ≥ 10mg/day prednisone (or equivalent) or < 3 months from allogenic hematopoietic cell transplant (HCT).
- Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; however, prophylactic use of these agents is acceptable even if parenteral.
- Major surgery within 2 weeks of first dose of study drug.
- Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety.
- Unstable cardiovascular function:
- Symptomatic ischemia, or
- Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on anti-arrhythmia therapy are excluded; 1st degree AV block or asymptomatic LAFB/RBBB will not be excluded), or
- Congestive heart failure (CHF) of NYHA Class ≥3, or
- Myocardial infarction (MI) within 3 months.
- Known active Hepatitis B or Hepatitis C infection (Hepatitis testing is not required as part of this study).
- Known human immunodeficiency virus (HIV) infection (HIV testing is not required as part of this study).
- Subject has received the following ≤ 7 days prior to Cycle 1, Day 1: Strong and moderate CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort.
- Subject has received the following ≤ 5 days prior to Cycle 1, Day 1: Strong and moderate CYP3A inhibitors such as fluconazole, ketoconazole, and clarithromycin.
- Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit ≤ 3 days prior to Cycle 1, Day 1.
- Inability to swallow oral medication; or the presence of a poorly controlled gastrointestinal disease, disorder, syndrome, or dysfunction that could significantly affect the absorption of oral study drug - e.g. Crohn's disease, ulcerative colitis, chronic diarrhea (defined as > 4 loose stools per day), malabsorption syndrome, or bowel obstruction.
- Inability or unwillingness to take required and recommended medications intended to prevent and treat potential adverse events of tumor lysis syndrome (TLS), nausea and vomiting, loss of appetite, and fatigue.
- Patients unwilling to comply with the protocol
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Roswell Park Cancer Center
Buffalo, New York, 14263
University Hospitals of Cleveland
Cleveland, Ohio, 44106
University of Texas Southwestern Medical Center
Dallas, Texas, 75390-8565
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
About this study
Official title: An Investigator-Sponsored Phase Ib Trial of Venetoclax and SINE: Selective Inhibition of Nuclear Export in Patients With High Risk Hematologic Malignancies
This phase Ib trial studies the toxicity and dosing of venetoclax in combination with selinexor, and how well the combination works in treatment of patients with high risk hematologic malignancies such as diffuse large B-cell lymphoma and acute myeloid leukemia that has come back (recurrent) or does not respond to initial treatment (refractory). Venetoclax functions by inhibiting a protein in the body called bcl-2, which is involved in slowing down the normal process by which old cells in the body are cleared (called apoptosis). Selinexor functions by trapping "tumor suppressing proteins" within the cell and causing the cancer cells to die or stop growing. This study examines the effects, if any, of selinexor and venetoclax on high risk hematologic malignancies and on the body, including any side-effects.
Read the detailed description
Primary:
- Escalation: Identify the maximum tolerated dose(s) (MTD) and recommended phase 2 dose(s) (RP2D) of SEL-VEN combination therapy in patients with diffuse large B-cell lymphoma (DLBCL) and acute myeloid leukemia (AML).
- Expansion: Determine the overall response rate of SEL-VEN combination therapy in patients with relapsed/refractory hematologic malignancies.
Exploratory Objectives:
- To explore biomarkers of response to SEL-VEN therapy.
- To determine the progression free survival (PFS) and overall survival (OS) of SEL-VEN combination therapy.
OUTLINE: This is a dose-escalation study.
Patients receive venetoclax orally (PO) once daily (QD) on days 1-28. Patients with DLBCL receive selinexor PO on days 1, 8, 15, and 22 of each cycle. Patients with venetoclax-naive AML are treated with selinexor on days 8, 15, and 22 of cycle 1, followed by days 1, 8, 15, and 22 of subsequent cycles. Venetoclax-refractory AML patients begin both drugs on cycle 1 day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 28 days and every 3 months for 2 years.
- Being tested
- Venetoclax, Selinexor
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Leukemia, Myeloid, Acute, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VenetoclaxDrug
Given by mouth
SelinexorDrug
Given by mouth
| Study group | Role | What they receive |
|---|---|---|
| Treatment (venetoclax, selinexor) | Experimental | Patients receive venetoclax PO QD on days 1-28. Patients with DLBCL receive selinexor PO on days 1, 8, 15, and 22 of each cycle. Venetoclax naïve AML patients receive selinexor on days 8, 15, and 22 of cycle 1, followed by days 1, 8, 15, and 22 of subsequent cycles. Venetoclax refractory AML patients receive selinexor PO on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Venetoclax; Drug: Selinexor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (escalation)
Measured: Up to 28 days
Overall response rate (expansion)
Measured: At 12 weeks
Secondary outcomes (2)
Progression free survival
Will be estimated using the Kaplan-Meier method with 95% confidence intervals. Descriptive statistics will be used to summarize survival outcomes among subgroups. Will be compared with historical controls of patients that received venetoclax monotherapy
Measured: Up to 2 years
Overall survival
Will be estimated using the Kaplan-Meier method with 95% confidence intervals. Descriptive statistics will be used to summarize survival outcomes among subgroups. Will be compared with historical controls of patients that received venetoclax monotherapy.
Measured: 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 posted20 May 2019
- Study start21 Jun 2019
- Primary completion1 Sep 2024
- Study completion1 Sep 2024
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 Diffuse Large B-cell LymphomaStudies 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
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanjay Mohan
- Sponsor type
- University, hospital or other
- Collaborators
- Karyopharm Therapeutics Inc, AbbVie
- Responsible party
- Sponsor-investigator, Sanjay Mohan, Vanderbilt-Ingram Cancer Center
- Investigators
- Sanjay Mohan, MD, Principal investigator, Vanderbilt Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03955783
- Sponsor's protocol ID
- VICC HEM 1755
- Other IDs
- NCI-2019-02953
- Status last verified
- Oct 2025
- First submitted
- 16 May 2019
- Last updated
- 29 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Investigator-Sponsored Phase Ib Trial of Venetoclax and SINE: Selective Inhibition of Nuclear Export in Patients With High Risk Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT03955783
- Acronym / sponsor ID
- VICC HEM 1755
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- Sanjay MohanUniversity, hospital or other
- Collaborators
- Karyopharm Therapeutics Inc, AbbVie
- Study start
- 21 Jun 2019 (actual)
- Primary completion
- 1 Sep 2024 (actual)
- Study completion
- 1 Sep 2024 (actual)
- First posted
- 20 May 2019 (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 Ib trial studies the toxicity and dosing of venetoclax in combination with selinexor, and how well the combination works in treatment of patients with high risk hematologic malignancies such as diffuse large B-cell lymphoma and acute myeloid leukemia that has come back (recurrent) or does not respond to initial treatment (refractory). Venetoclax functions by inhibiting a protein in the body called bcl-2, which is involved in slowing down the normal process by which old cells in the body are cleared (called apoptosis). Selinexor functions by trapping "tumor suppressing proteins" within the cell and causing the cancer cells to die or stop growing. This study examines the effects, if any, of selinexor and venetoclax on high risk hematologic malignancies and on the body, including any side-effects.
Detailed description
Primary:
- Escalation: Identify the maximum tolerated dose(s) (MTD) and recommended phase 2 dose(s) (RP2D) of SEL-VEN combination therapy in patients with diffuse large B-cell lymphoma (DLBCL) and acute myeloid leukemia (AML).
- Expansion: Determine the overall response rate of SEL-VEN combination therapy in patients with relapsed/refractory hematologic malignancies.
Exploratory Objectives:
- To explore biomarkers of response to SEL-VEN therapy.
- To determine the progression free survival (PFS) and overall survival (OS) of SEL-VEN combination therapy.
OUTLINE: This is a dose-escalation study.
Patients receive venetoclax orally (PO) once daily (QD) on days 1-28. Patients with DLBCL receive selinexor PO on days 1, 8, 15, and 22 of each cycle. Patients with venetoclax-naive AML are treated with selinexor on days 8, 15, and 22 of cycle 1, followed by days 1, 8, 15, and 22 of subsequent cycles. Venetoclax-refractory AML patients begin both drugs on cycle 1 day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 28 days and every 3 months for 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (venetoclax, selinexor) | Experimental | Drug: Venetoclax, Drug: SelinexorPatients receive venetoclax PO QD on days 1-28. Patients with DLBCL receive selinexor PO on days 1, 8, 15, and 22 of each cycle. Venetoclax naïve AML patients receive selinexor on days 8, 15, and 22 of cycle 1, followed by days 1, 8, 15, and 22 of subsequent cycles. Venetoclax refractory AML patients receive selinexor PO on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure.
- Age ≥ 18 years
- Life expectancy > 12 weeks.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Histologically confirmed diagnosis of one of the following, in accordance with WHO diagnostic criteria:
Key exclusion criteria (23 listed)
- Patients who are pregnant or lactating
- Patients who received any systemic anticancer therapy including investigational agents or radiation ≤3 weeks (or ≤5 half-lives of the drug [whichever is shorter]) prior to C1D1. Hydroxyurea is permitted for up to 14 days in AML patients
- Inadequate recovery from toxicity attributed to prior anti-cancer therapy. With the exception of alopecia or fatigue, patients must have recovered to baseline or ≤ Grade 1 (NCI-CTCAE v4.03) residual toxicity prior to first dose of protocol-indicated treatment.
- Participation in another clinical trial with any investigational drug within 14 days prior to study enrollment.
- Patients included in the VEN refractory cohort that have discontinued venetoclax therapy (either monotherapy or combination) due to toxicity or hypersensitivity, including prior history of grade 3/4 TLS during prior VEN exposure
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 |
|---|---|---|
| VenetoclaxGiven by mouth | Drug | Treatment (venetoclax, selinexor) |
| SelinexorGiven by mouth | Drug | Treatment (venetoclax, selinexor) |
Primary outcome
Maximum tolerated dose (escalation)
Time frame: Up to 28 days
Overall response rate (expansion)
Time frame: At 12 weeks
2 secondary outcomes
Progression free survival
Time frame: Up to 2 years
Overall survival
Time frame: Up to 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 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: No
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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. This study is not recruiting at the moment.
Sanjay Mohan, MD principal investigator
Vanderbilt Medical Center
4 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 Venetoclax and Selinexor in people with Diffuse Large B-cell Lymphoma and Acute Myeloid Leukemia, run by Sanjay Mohan at 4 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 22 inclusion and 23 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: finished, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (escalation) (time frame: Up to 28 days). 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 NCT03955783, 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 29 Oct 2026; AzTrials last refreshed its copy on 8 Nov 2026.