Venetoclax, Ixazomib Citrate, and Dexamethasone in Treating Patients with Relapsed Multiple Myeloma

NCT03399539 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: MC168CNCI-2017-0245616-008629
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I trial studies the side effects and best dose of venetoclax when given together with ixazomib citrate and dexamethasone and to see how well they work in treating patients with multiple myeloma that has come back. Venetoclax and ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax together with ixazomib citrate and dexamethasone may work better in treating patients with multiple myeloma.

Conditions

Recurrent Plasma Cell Myeloma; T(11;14)

Outcome Measures

Primary Outcomes (6)

• Maximum tolerated dose (MTD) of venetoclax in combination with ixazomib and dexamethasone (Phase 1)

  Defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients (at least 2 of a maximum of 6 new patients). Will be examined in an exploratory and hypothesis-generating fashion.

  Up to 28 days

• Overall survival

  The distribution of overall survival will be estimated using the method of Kaplan-Meier.

  Time from registration to death due to any cause, assessed up to 3 years

• Progression-free survival

  The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.

  Time from registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 3 years

• Rate of confirmed response defined as a patient who has achieved an stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) on two consecutive evaluations (Phase 2)

  The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

  Up to 3 years

• Rate of confirmed response in patients with t(11;14) translocation

  Will be estimated by the number of patients with a confirmed sCR, CR, VGPR, or PR divided by the total number of evaluable patients with t(11;14) translocation. Exact binomial 95% confidence intervals for the true success proportion will be calculated.

  Up to 3 years

• Rate of CR defined as the number of patients with an sCR or CR divided by the total number of evaluable patients

  Exact binomial 95% confidence intervals for the true success proportion will be calculated.

  Up to 3 years

Secondary Outcomes (1)

• Incidence of adverse events

  Up to 3 years

Study Arms (1)

Treatment (venetoclax, ixazomib citrate, dexamethasone)

EXPERIMENTAL

Patients receive venetoclax PO daily on days 1-28, ixazomib citrate PO once weekly on days 1, 8, and 15, and dexamethasone PO on days 1, 8, 15, and 22 for courses 1-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Dexamethasone; Drug: Ixazomib Citrate; Other: Laboratory Biomarker Analysis; Drug: Venetoclax

Interventions

Dexamethasone DRUG

Given PO

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, Visumetazone

Treatment (venetoclax, ixazomib citrate, dexamethasone)

Ixazomib Citrate DRUG

Given PO

Also known as: MLN-9708, MLN9708, Ninlaro

Treatment (venetoclax, ixazomib citrate, dexamethasone)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (venetoclax, ixazomib citrate, dexamethasone)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta

Treatment (venetoclax, ixazomib citrate, dexamethasone)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Phase 1: Relapsed MM with at least one prior line of therapy and should have received a proteasome inhibitor and an immunomodulatory drug
• Phase 2: 1-3 prior lines of therapy and should have received a proteasome inhibitor and an immunomodulatory drug
• Obtained =\< 14 days prior to registration: Calculated creatinine clearance (using Cockcroft-Gault equation) \>= 30 mL/min
• Obtained =\< 14 days prior to registration: Absolute neutrophil count (ANC) \>= 1000/uL (without growth factor support)
• Obtained =\< 14 days prior to registration: Un-transfused platelet count \>= 75000/uL (\>= 50,000/uL if marrow plasma cells \[PC\]% \> 50%)
• Obtained =\< 14 days prior to registration: Hemoglobin \>= 8.0 g/dL
• Obtained =\< 14 days prior to registration: Total bilirubin =\< 1.5 x upper limit of normal (ULN)
• Obtained =\< 14 days prior to registration: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN
• Obtained =\< 14 days prior to registration: Alkaline phosphatase =\< 750 U/L
• Expansion cohort only: Plasma cell fluorescence in situ hybridization (FISH) test demonstrating presence of t(11;14)
• Measurable disease of multiple myeloma as defined by at least ONE of the following:
• Serum monoclonal protein \>= 1.0 g/dL
• \> 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
• Serum immunoglobulin free light chain \>= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

You may not qualify if:

• Diagnosed or treated for another malignancy =\< 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease; NOTE: Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
• Any of the following:
• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception
• Other co-morbidity which would interfere with patient's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
• Other concurrent chemotherapy or any ancillary therapy considered investigational
• NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
• Peripheral neuropathy \>= grade 2 on clinical examination or grade 1 with pain during the screening period
• Major surgery =\< 14 days prior to study registration
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject?s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies) or active hepatitis
• Administration of a strong or moderate CYP3A inhibitor or inducer =\< 14 days prior to registration
• Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
• Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial

Sponsors & Collaborators

• Mayo Clinic: lead
• Multiple Myeloma Research Foundation: collaborator

Study Sites (3)

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Siteman Cancer Center at Washington University

St Louis, Missouri, 63110, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; ixazomib; venetoclax

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Shaji Kumar, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2018
• First Posted: January 16, 2018
• Study Start: May 2, 2018
• Primary Completion: December 20, 2021
• Study Completion: February 23, 2024
• Last Updated: November 4, 2024

Record last verified: 2024-10

Locations

US (3)