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

NCT ID: NCT05391750

Last Updated: 2025-01-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-19
• Study Completion Date: 2027-02-12

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 treatment (refractory). Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Tocilizumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Tocilizumab is used to treat side effects from immune therapy in patients with myeloma. Giving venetoclax and tocilizumab may kill more cancer cells.

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

SECONDARY OBJECTIVES:

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.

TERTIARY/EXPLORATORY OBJECTIVES:

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.

Conditions

Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (venetoclax, tocilizumab)

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

Group Type: EXPERIMENTAL

Tocilizumab

Intervention Type: BIOLOGICAL

Given IV

Venetoclax

Intervention Type: DRUG

Given PO

Interventions

Tocilizumab

Given IV

Intervention Type: BIOLOGICAL

Venetoclax

Given PO

Intervention Type: DRUG

Other Intervention Names

Actemra; Immunoglobulin G1, Anti-(Human Interleukin 6 Receptor) (Human-Mouse Monoclonal MRA Heavy Chain), Disulfide with Human-Mouse Monoclonal MRA Kappa-Chain, Dimer; MRA; R-1569; RoActemra; ABT-0199; ABT-199; ABT199; GDC-0199; RG7601; Venclexta; Venclyxto

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Jonathan Kaufman

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jonathan L. Kaufman, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jonathan L. Kaufman, MD

Role: CONTACT

jlkaufm@emory.edu

404-778-1900

Facility Contacts

Bryan Burton

Role: primary

bjburto@emory.edu

404-778-1780

Other Identifiers

NCI-2021-02510

Identifier Type: REGISTRY

Identifier Source: secondary_id

STUDY00002448

Identifier Type: -

Identifier Source: secondary_id

WINSHIP5273-21

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA138292

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00002448

Identifier Type: -

Identifier Source: org_study_id