Status:
RECRUITING
Venetoclax and Tocilizumab for the Treatment of Patients With Relapsed or Refractory t(11;14) Multiple Myeloma
Lead Sponsor:
Emory University
Collaborating Sponsors:
National Cancer Institute (NCI)
Conditions:
Recurrent Plasma Cell Myeloma
Refractory Plasma Cell Myeloma
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief Summary
This phase I trial finds out the best dose and side effects of venetoclax and tocilizumab in treating patients with t(11;14) multiple myeloma that has come back (relapsed) or does not respond to treat...
Detailed Description
PRIMARY OBJECTIVE: I. To determine the dose limiting toxicity (DLT), safety profile, and the recommended phase 2 dose (RPTD) of venetoclax and tocilizumab when administered in subjects with relapsed ...
Eligibility Criteria
Inclusion
- Subject must be \>= 18 years of age Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of =\< 2
- Diagnosis of multiple myeloma that requires treatment and has been previously treated with:
- Has received at least 2 prior lines of therapy
- Has had documented disease progression on or within 60 days after completion of the last therapy.
- Has received at least 2 consecutive cycles of lenalidomide and be relapsed/refractory to lenalidomide, as defined per protocol.
- Has received at least 2 consecutive cycles of a proteasome inhibitor (PI). Have MM positive for t(11;14) translocation as determined by an analytically validated fluorescence in-situ hybridization (FISH) assay per the central laboratory testing
- Subject must have had measurable disease at Screening, defined as any of the following:
- Serum monoclonal protein \>= 1.0 g/dL (\>= 10 g/L) by protein electrophoresis, or
- \>= 200 mg of monoclonal protein in the urine on 24-hour electrophoresis, or
- Serum immunoglobulin free light chain (FLC) \>= 10 mg/dL provided serum FLC ratio is abnormal
- Subjects with a history of autologous transplantation must have adequate peripheral blood counts as defined below, have recovered from any transplant related toxicity(s) and be \> 100 days post-autologous transplant (prior to first dose of study drug)
- Subjects must meet the following laboratory parameters, per laboratory reference range, at least once during the screening period:
- Absolute neutrophil count (ANC) \>= 1000/uL (Subject may use granulocyte colony-stimulating factor \[G-CSF\] to achieve ANC eligibility criteria)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 1.5 x upper limit of normal range (ULN)
- Calculated creatinine clearance \>= 30 mL/min using a modified Cockcroft- Gault calculation or a 24-hour urine collection for creatinine clearance
- Platelet count \>= 75,000 cells/mm3 and independent of transfusion for 2 weeks
- Hemoglobin \>= 8.0 g/dL, subjects may not receive blood transfusion within 1 week to achieve hemoglobin eligibility criteria per investigator discretion
- Total bilirubin =\< 1.5 x ULN; subjects with Gilbert's syndrome may have bilirubin \> 1.5 x ULN
- If female, subject must be:
- Postmenopausal defined as:
- Age \> 55 years with no menses for 24 or more months without an alternative medical cause
- Age =\< 55 years with no menses for 24 or more months without an alternative medical cause
- AND an follicle stimulating hormone (FSH) level \> 40 IU/L. OR
- Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy) OR
- A woman of childbearing potential (WOCP) practicing at least one protocol specified method of birth control starting at cycle 1 day 1 (or earlier) through at least 30 days after last dose of study drug
- Females of childbearing potential (must have negative results for pregnancy test performed:
- At screening, on a serum or urine sample obtained within 28 days prior to the first study drug administration,
- Prior to dosing, on a urine sample obtained on the first day of study drug dosing, if it has been \> 7 days since obtaining the serum pregnancy test results
- Females of non-childbearing potential (either postmenopausal or permanently surgically sterile as defined above) at screening do not require pregnancy testing
- Must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures
- Exclusion Criteria:
- Subject exhibits evidence of other clinically significant uncontrolled condition(s), including, but not limited to:
- Acute infection within 14 days prior to first dose of study drug requiring antibiotic, antifungal, or antiviral therapy
- Diagnosis of fever and neutropenia within 1 week prior to first dose of study drug
- Subject has a cardiovascular disability status of New York Heart Association class \>= 3
- Subject has a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular or hepatic disease within the last 6 months that, in the opinion of the investigator, would adversely affect his/her participation in the study
- Subject has a history of other active malignancies other than multiple myeloma within the past 3 years prior to study entry, with the following exceptions:
- Adequately treated in situ carcinoma of the cervix uteri,
- Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin,
- Localized prostate cancer Gleason grade 6 or lower AND with stable prostate specific antigen (PSA) levels off treatment
- Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent
- Known human immunodeficiency viral (HIV) infection
- Active hepatitis B or C infection based on screening blood testing
- Subject is receiving other ongoing anti-myeloma therapy
- Subject has received any of the following within 7 days prior to the first dose of study drug:
- Strong or moderate CYP3A inhibitors, or
- Strong or moderate CYP3A inducers
- Subject has received any of the following within 14 days prior to the first dose of study drug or has not recovered to less than a grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy: any anti-myeloma therapy including chemotherapy, radiotherapy, or investigational therapy, including targeted small molecule agents
- Subject has received prior treatment with a BCL-2 family inhibitor
- Subject is pregnant, parturient, or breastfeeding; deprived of freedom by judicial or administrative decision; hospitalized and unable to provide consent, or otherwise unable to provide consent
- Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or star fruit within 3 days prior to the first dose of study drug
- Subject has received immunization with live vaccine within 60 days of dosing
- Recent corticosteroid therapy at a cumulative dose equivalent to \> 140 mg of prednisone or a single dose equivalent to \>= 40 mg of dexamethasone within 2 weeks prior to the first dose of study drug
- Subject's decision to not divulge the race
Exclusion
Key Trial Info
Start Date :
October 19 2022
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
February 12 2027
Estimated Enrollment :
72 Patients enrolled
Trial Details
Trial ID
NCT05391750
Start Date
October 19 2022
End Date
February 12 2027
Last Update
January 24 2025
Active Locations (1)
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1
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States, 30322