Recurrent Plasma Cell MyelomaPhase 1NCT03399539
Venetoclax, Ixazomib Citrate, and Dexamethasone in Treating Patients with Relapsed Multiple Myeloma
A Phase 1 study testing Dexamethasone, Ixazomib Citrate and Laboratory Biomarker Analysis in people with Recurrent Plasma Cell Myeloma and T(11;14), run by Mayo Clinic at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Plasma Cell Myeloma, T(11;14)
- What is being tested?
- Dexamethasone, Ixazomib Citrate and Laboratory Biomarker Analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 3 sitesUnited States
- Study dates
- 2 May 2018to 23 Feb 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
- 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
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- 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
- Provide written informed consent
- Negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
- Willing to follow strict birth control measures as suggested by the study
- Female patients: If they are of childbearing potential, must agree to one of the following:
- Practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, AND must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
- Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
- Male patients: even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following:
- Agree to practice effective barrier contraception during the entire study treatment period and through 120 days after the last dose of study drug, OR
- Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods and withdrawal are not acceptable methods of contraception)
- Life expectancy >= 12 weeks
- Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
- Willing to provide research bone marrow aspirate specimen
Who cannot join
- 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
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- 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
- Failure to have fully recovered (i.e., =< grade 1 toxicity) from the reversible effects of prior chemotherapy
- Radiotherapy =< 14 days prior to registration; Note: If the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib
- Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing
- Previous treatment with ixazomib, or participated in a blinded study with ixazomib
- Live-virus vaccines =< 28 days prior to registration
- Heart failure > New York Heart Association (NYHA) class II
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109
Mayo Clinic
Rochester, Minnesota, 55905
Siteman Cancer Center at Washington University
St Louis, Missouri, 63110
About this study
Official title: Phase I Clinical Trial of Venetoclax (ABT-199) in Combination with Ixazomib and Dexamethasone for Patients with Relapsed Multiple Myeloma
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of venetoclax in combination with ixazomib citrate (ixazomib) and dexamethasone in patients with relapsed multiple myeloma (MM). (Phase 1)
SECONDARY OBJECTIVES:
- To describe toxicities associated with venetoclax, in combination with ixazomib and dexamethasone in patients with relapsed MM. (Phase 1)
TERTIARY OBJECTIVES:
- To explore levels of BCL-2 family member proteins (BCL-2, BCL-x, MCL-1) on bone marrow biopsies using ribonucleic acid sequencing (RNASeq) and immunohistochemistry.
OUTLINE: This is a phase I, dose-escalation study of venetoclax followed by a phase II study.
Patients receive venetoclax orally (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.
After completion of study treatment, patients are followed up every 3 or 6 months for 3 years.
- Conditions
- Recurrent Plasma Cell Myeloma, T(11;14)
- Being tested
- Dexamethasone, Ixazomib Citrate, Laboratory Biomarker Analysis, Venetoclax
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex
Given PO
Ixazomib CitrateDrug
Also called MLN-9708, MLN9708, Ninlaro
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
VenetoclaxDrug
Also called ABT-0199, ABT-199, ABT199, GDC-0199
Given PO
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Dexamethasone; Drug: Ixazomib Citrate; Other: Laboratory Biomarker Analysis; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 28 days
Overall survival
The distribution of overall survival will be estimated using the method of Kaplan-Meier.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 3 years
Secondary outcomes (1)
Incidence of adverse events
The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2018
- Study start2 May 2018
- Primary completion20 Dec 2021
- Study completion23 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Plasma Cell MyelomaStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- 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
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Multiple Myeloma Research Foundation
- Responsible party
- Sponsor
- Investigators
- Shaji Kumar, M.D., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03399539
- Sponsor's protocol ID
- MC168C
- Other IDs
- NCI-2017-02456, MC168C, 16-008629
- Status last verified
- Oct 2024
- First submitted
- 9 Jan 2018
- Last updated
- 4 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Clinical Trial of Venetoclax (ABT-199) in Combination with Ixazomib and Dexamethasone for Patients with Relapsed Multiple Myeloma
- ClinicalTrials.gov ID
- NCT03399539
- Acronym / sponsor ID
- MC168C
- Conditions
- Recurrent Plasma Cell Myeloma, T(11;14)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- Multiple Myeloma Research Foundation
- Study start
- 2 May 2018 (actual)
- Primary completion
- 20 Dec 2021 (actual)
- Study completion
- 23 Feb 2024 (actual)
- First posted
- 16 Jan 2018 (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 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.
Detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of venetoclax in combination with ixazomib citrate (ixazomib) and dexamethasone in patients with relapsed multiple myeloma (MM). (Phase 1)
SECONDARY OBJECTIVES:
- To describe toxicities associated with venetoclax, in combination with ixazomib and dexamethasone in patients with relapsed MM. (Phase 1)
TERTIARY OBJECTIVES:
- To explore levels of BCL-2 family member proteins (BCL-2, BCL-x, MCL-1) on bone marrow biopsies using ribonucleic acid sequencing (RNASeq) and immunohistochemistry.
OUTLINE: This is a phase I, dose-escalation study of venetoclax followed by a phase II study.
Patients receive venetoclax orally (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.
After completion of study treatment, patients are followed up every 3 or 6 months for 3 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, ixazomib citrate, dexamethasone) | Experimental | Drug: Dexamethasone, Drug: Ixazomib Citrate, Other: Laboratory Biomarker Analysis, Drug: VenetoclaxPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- 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%)
Key exclusion criteria (21 listed)
- 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:
- 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
- Peripheral neuropathy >= grade 2 on clinical examination or grade 1 with pain during the screening period
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 |
|---|---|---|
| DexamethasoneAlso: Aacidexam, Adexone, Aknichthol Dexa, Alba-DexGiven PO | Drug | Treatment (venetoclax, ixazomib citrate, dexamethasone) |
| Ixazomib CitrateAlso: MLN-9708, MLN9708, NinlaroGiven PO | Drug | Treatment (venetoclax, ixazomib citrate, dexamethasone) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (venetoclax, ixazomib citrate, dexamethasone) |
| VenetoclaxAlso: ABT-0199, ABT-199, ABT199, GDC-0199Given PO | Drug | Treatment (venetoclax, ixazomib citrate, dexamethasone) |
Primary outcome
Maximum tolerated dose (MTD) of venetoclax in combination with ixazomib and dexamethasone (Phase 1)
Time frame: Up to 28 days
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.
Overall survival
Time frame: Time from registration to death due to any cause, assessed up to 3 years
The distribution of overall survival will be estimated using the method of Kaplan-Meier.
Progression-free survival
Time frame: Time from registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 3 years
The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.
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)
Time frame: Up to 3 years
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.
Rate of confirmed response in patients with t(11;14) translocation
Time frame: Up to 3 years
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.
Rate of CR defined as the number of patients with an sCR or CR divided by the total number of evaluable patients
Time frame: Up to 3 years
Exact binomial 95% confidence intervals for the true success proportion will be calculated.
1 secondary outcome
Incidence of adverse events
Time frame: Up to 3 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 4 Nov 2024.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
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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.
Shaji Kumar, M.D. principal investigator
Mayo Clinic
3 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 Dexamethasone, Ixazomib Citrate and Laboratory Biomarker Analysis in people with Recurrent Plasma Cell Myeloma and T(11;14), run by Mayo Clinic at 3 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 27 inclusion and 21 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 4 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 (MTD) of venetoclax in combination with ixazomib and dexamethasone (Phase 1) (time frame: Up to 28 days). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Nov 2024.