Venetoclax and Tocilizumab for the Treatment of Patients With Relapsed or Refractory t(11;14) Multiple Myeloma VENETOCLAX AND TOCILIZUMAB FOR T(11;14)

What's the purpose of this trial?

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 treatment (refractory).

This trial is currently open and accepting patients.

What will happen during the trial?


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 and recurrent (RR) multiple myeloma t(11;14) (MM).


I. To evaluate the preliminary efficacy data regarding the effect of venetoclax and tocilizumab by objective response rate per IMWG criteria.

II. To evaluate the effect of chronic tocilizumab administration on venetoclax exposure.


I. To evaluate the preliminary efficacy data regarding the effect of venetoclax and tocilizumab by time to response (TTR), time to disease progression (TTP), duration of response (DOR), progression free survival (PFS) and overall survival (OS).

II. To measure the effect of IL6 receptor blockade on ex vivo venetoclax sensitivity.

III. To evaluate the cell populations in the bone marrow of responders versus non-responders as well as the effect of IL6 receptor blockade on those populations.

IV. To evaluate the expression of B cell markers on venetoclax sensitive myeloma.

V. To determine the expression of key BCL2 family members with and without IL6 receptor blockade.

VI. To correlate differences in somatic mutations, structural alterations, gene expression and chromatin accessibility with venetoclax response.

OUTLINE: This is a dose-escalation study of venetoclax and tocilizumab.

Patients receive tocilizumab intravenously (IV) on day -7 of cycle 1, and on day 1 of subsequent cycles. Patients also receive venetoclax orally (PO) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks, then every 6 months thereafter.

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

Inclusion Criteria:

  • 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:
    • >= 3 prior line of therapy. Have received treatment with a proteasome inhibitor, an immunomodulatory (IMiD) agent (e.g., thalidomide, lenalidomide, pomalidomide) and a CD38 monoclonal antibody
    • 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)
  • 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

Additional Trial Information

Phase 1

Enrollment: 72 patients (estimated)

View More

Trial Locations

All Trial Locations

View all clinical trial locations sorted by state.


Winship Cancer Institute Emory University

Atlanta, GA

Open and Accepting
Interested in this trial?
  • Call us today 😀 keyboard_arrow_right

    We know how difficult and confusing this process can be. If you are interested in this clinical trial or have questions, you can call us at any time. You can also send us a direct message with questions.

    (888) 828-2206
  • If you are interested in keeping an eye on this trial, you can add it to your list of favorite trials. We'll send you alerts when this trial is updated.

  • Talk to your doctor keyboard_arrow_right

    You can print an overview of this trial to take in to your next appointment. Your doctor can help you understand if this trial may be right for you.

Still need help? Send us a message

SparkCures Verified

Learn more about how we work with trial sponsors