NCT02477215 · REGISTRY CONDITION SEARCH

Study of Bendamustine and IXAZOMIB (MLN9708) Plus Dexamethasone in Relapsed/Refractory Multiple Myeloma

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1, PHASE2
Status at capture: COMPLETED
Registry last update: 2020-10-22

This Phase I/II study is designed to first identify doses of MLN9708 and bendamustine that are associated with an acceptable adverse event profile when delivered together in 28-day cycles. Additionally, the study aims to assess the efficacy of the combination in patients with relapsed/refractory multiple myeloma. Responders (stable disease or more), will continue to receive up to eight cycles total in the absence of further progressive disease.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

Maximum Tolerated Dose of Bendamustine

→

outcome · POSTED

Objective Response Rate

→

outcome · POSTED

Overall Survival (OS)

→

outcome · POSTED

Progression Free Survival (PFS)

→

outcome · POSTED

Cumulative Response Rates in Patients After Eight Cycles.

→

outcome · POSTED

Duration of Response (DoR)

→

outcome · POSTED

Number of Participants Experiencing Dose-Limiting Toxicity (DLT)

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

eligibility Criteria: INCLUSION CRITERIA: 1. Male or female patients 18 years or older. 2. Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care. 3. Female patients who: * Are postmenopausal for at least one year before the screening visit, OR * Are surgically sterile, OR * If they are of childbearing potential, agree to practice two 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, OR • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[eg, calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception.) Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following: * Agree to practice effective barrier contraception during the entire study treatment period and through 90 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 (eg, calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are not acceptable methods of contraception.) 4. Patients must have have histologically or cytologically confirmed symptomatic Multiple Myeloma, who are non-responsive to or ineligible for autologous stem cell transplant, and who progress after prior exposure to proteasome inhibitor (bortezomib, carfilzomib) and lenalidomide or pomalidomide or thalidomide (IMID); and refractory/progressing to at least one of these agents and must meet at least one of the following parameters of measurable disease: * Measurable levels of monoclonal protein (M protein): \> 1 g/dL of immunoglobin G (IgG) or immunoglobin M (IgM) M-protein or \> 0.5 g/dL immunoglobin A (IgA) or immunoglobin D (IgD) M protein on serum protein electrophoresis OR \> 200 mg/24h of free light chain proteinuria on a 24 hour urine protein electrophoresis which must be obtained within 4 weeks prior to registration OR \> 10 mg/dL involved free light chain on serum free light chain testing with an abnormal kappa:lambda light chain ratio. * Patients with lytic bone disease, defined as at least one lytic lesion that can be accurately measured in at least one dimension. 5. Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2. 6. Patients are eligible after autologous or allogeneic stem cell transplantation. Allogeneic transplantation can be enrolled only if they have no ongoing transplant related side effects. 7. Patients must be at least 2 weeks from major surgery, radiation therapy, participation in other investigational trials and have recovered from clinically significant toxicities of these prior treatments 8. Patients must meet the following clinical laboratory criteria: * Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet count ≥ 75,000/mm3. Platelet transfusions or granulocyte-colony stimulating factor (G-CSF) can be used to help patients meet eligibility criteria but are not allowed within 3 days before study enrollment. * Total bilirubin \< 1.5 x the upper limit of the normal range (ULN), , OR, direct bilirubin within normal limits (WNL), when total bilirubin is \>\>\< 1.5 x the ULN. * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 3 x ULN. * Calculated creatinine clearance ≥ 30 mL/min. EXCLUSION CRITERIA Patients meeting any of the following exclusion criteria are not to be enrolled in the study: 1. Female patients who are lactating or have a positive serum pregnancy test during the screening period. 2. Failure to have fully recovered (ie, ≤ Grade 1 toxicity) from the reversible effects of prior chemotherapy except for peripheral neuropathy, which is addressed in exclusion criteria no. #14. 3. Major surgery within 14 days before enrollment. 4. Radiotherapy within 14 days before enrollment. If the involved field is limited (single disease focus not involving pelvis and involving \<36 Gy radiation), 7 days will be considered a sufficient interval between treatment and administration of Ixazomib provided hematologic inclusion parameters are met. 5. Central nervous system involvement. 6. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment. 7. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months. 8. Systemic treatment, within 14 days before the first dose of IXAZOMIB, with strong inhibitors of cytochrome P1A2 (CYP1A2) (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of cytochrome P3A (CYP3A) (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort. 9. Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive. 10. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol. 11. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent. 12. Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of IXAZOMIB including difficulty swallowing. 13. Diagnosed or treated for another malignancy where the expected survival is less than two years will be excluded. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection. 14. Patient has ≥ Grade 2 peripheral neuropathy, or Grade 2 with pain on clinical examination during the screening period. 15. 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. 16. Patients that have previously been treated with IXAZOMIB, or participated in a study with IXAZOMIB whether treated with IXAZOMIB or not. 17. Patients with a history of severe chronic obstructive pulmonary disease requiring ongoing oxygen support or those with a resting oxygen saturation \<92% on room air irrespective of the cause.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Ixazomib 4 mg, days 1, 8, 15. Dexamethasone 40 mg oral weekly. Bendamustine dose levels: 70 mg/m\^2, 80mg/m\^2, or 90 mg/m\^2 given on days 1 and 2
intervention Names
Drug: MLN9708
Drug: Dexamethasone
Drug: Bendamustine (multiple dose levels)
label
MLN9708, Bendamustine and Dexamethasone Dose Escalation
type
EXPERIMENTAL
description
Ixazomib 4 mg, days 1, 8, 15. Dexamethasone 40 mg oral weekly. Bendamustine dose levels: MTD given on days 1 and 2
intervention Names
Drug: MLN9708
Drug: Dexamethasone
Drug: Bendamustine (MTD)
label
MLN9708, Bendamustine and Dexamethasone MTD
type
EXPERIMENTAL

interventions

arm Group Labels
MLN9708, Bendamustine and Dexamethasone Dose Escalation
MLN9708, Bendamustine and Dexamethasone MTD
description
4 mg of MLN9708 delivered on days 1, 8 and 15 of a 28 day cycle.
name
MLN9708
other Names
Ixazomib
type
DRUG
arm Group Labels
MLN9708, Bendamustine and Dexamethasone Dose Escalation
MLN9708, Bendamustine and Dexamethasone MTD
description
40 mg oral on Days 1, 8, 15 of each 28 day cycle.
name
Dexamethasone
other Names
Decadron
type
DRUG
arm Group Labels
MLN9708, Bendamustine and Dexamethasone Dose Escalation
description
70 mg/m\^2, 80 mg/m\^2, or 90 mg/m\^2 on days 1 and 2
name
Bendamustine (multiple dose levels)
other Names
Treanda
Treakisym
Ribomustin
type
DRUG
arm Group Labels
MLN9708, Bendamustine and Dexamethasone MTD
description
80 mg/m\^2 on days 1 and 2
name
Bendamustine (MTD)
other Names
Treanda
Treakisym
Ribomustin
type
DRUG

Study design

allocation

NON_RANDOMIZED

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 38
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Maximum tolerated dose of bendamustine in combination with fixed doses of ixazomib (MLN9708) and dexamethasone will be determined from the incidence of dose limiting toxicities at each dosage.
measure
Maximum Tolerated Dose of Bendamustine
time Frame
Six months for each dosing cohort
description
Objective response rate was defined as the number of subjects achieving a complete response (CR) or partial response (PR) after at least four cycles of ixazomib (MLN9708) and bendamustine plus dexamethasone.
measure
Objective Response Rate
time Frame
18 months

secondary Outcomes

description
Overall survival was determined as the average number of months subjects survived following enrollment.
measure
Overall Survival (OS)
time Frame
36 months
description
This measure is the number of months participants remain free from evidence of disease.
measure
Progression Free Survival (PFS)
time Frame
18 months
description
Percentage of subject response rates at any point during the eight cycles.
measure
Cumulative Response Rates in Patients After Eight Cycles.
time Frame
18 months
description
Median time in months participants maintain CR, PR or stable disease.
measure
Duration of Response (DoR)
time Frame
36 months
description
A 3+3 design was employed. At each dose, three patients were initially evaluated. If no dose limiting toxicities were observed, the bendamustine dose was increased; if one dose limiting toxicity is observed, three additional patients were treated at that dose. A dose at which 2 DLTs were observed in 3 or 6 patients were judged to be too toxic and the lower dose was defined as the maximally tolerated dose (MTD).
measure
Number of Participants Experiencing Dose-Limiting Toxicity (DLT)
time Frame
Six months

Full study description

brief Summary: This Phase I/II study is designed to first identify doses of MLN9708 and bendamustine that are associated with an acceptable adverse event profile when delivered together in 28-day cycles. Additionally, the study aims to assess the efficacy of the combination in patients with relapsed/refractory multiple myeloma. Responders (stable disease or more), will continue to receive up to eight cycles total in the absence of further progressive disease.
detailed Description: OVERVIEW: This Phase I/II study is designed to first identify doses of MLN9708 and bendamustine that are associated with an acceptable adverse event profile when delivered together in 28-day cycles. Additionally, the study aims to assess the efficacy of the combination in patients with relapsed/refractory multiple myeloma. Responders (stable disease or more),will continue to receive up to eight cycles total in the absence of further progressive disease. OVERVIEW OF THE DOSE ESCALATION/DE-ESCALATION: This study aims to assess the combination's efficacy in patients with relapsed/refractory multiple myeloma. Responders (stable disease or more) will continue to receive up to eight cycles total in the absence of further progressive disease. The dose of MLN9708 will be fixed at 4 mg given on days 1, 8 and 15. Dexamethasone will be administered at 40 mg (oral) on Days 1, 8, 15 of each 28 day cycle. Dexamethasone administered as 40 mg oral on Days 1, 8, 15 of each 28 day cycle. Three doses of bendamustine will be evaluated (Dose 1: 70 mg/m\^2, days 1 and 2; Dose 2: 80 mg/m\^2. days 1 and 2; and Dose 3: 90 mg/m\^2, days 1 and 2). PHASE 1 DESIGN: A 3+3 design was employed. At each dose, three patients were initially evaluated. When no dose limiting toxicities were observed, the bendamustine dose will be increased. PHASE 2 DESIGN: Design for Phase II portion of study: The MTD or a recommended phase 2 dose (RP2D) for the combination. The plan is to treat additional patients at that dose to assess efficacy and response to treatment. The investigators plan to enroll 19 patients (including those treated at the MTD in Phase I).

Source references

Source notices and limitations

Discovery and provenance

release id
ctgov-registry-1336d216cbd1bbff780dac70
edge id
nct-edge-2ddc00bd97284b5b5dce
requested nct id
NCT02477215
primary nct id
NCT02477215
source kind
ctgov_condition_query
source url
https://clinicaltrials.gov/api/v2/studies?query.cond=Plasma+Cell+Neoplasms&filter.advanced=AREA%5BHasResults%5Dtrue&pageSize=1000&format=json&countTotal=true
source record id
Source null
source file sha256
2314ce01316b2d7044d298c6d25eda12e99cc5f44273bc75efed6cd5e03a8c14
payload sha256
0a4160f0bff1540b0ef53d36f084c1a951e1bdfa229a52ada9bddd2da08ab00f
payload
clinical indication matching status
condition_index_match_asserted_by_registry_not_reviewed
end exclusive
true
id
nct-edge-2ddc00bd97284b5b5dce
link basis
returned_by_explicit_condition_and_posted_results_filter_query
nct id
NCT02477215
occurrences
context exact
NCT02477215
end
11
exact text
NCT02477215
start
0
offset unit
unicode_code_points
query cond
Plasma Cell Neoplasms
query disease state id
ds-plasma-cell-neoplasms
source file
/Users/arunverma/Documents/ChatGPT/Cancer Statistics Website/research-data/2026-09-10/clinicaltrials-condition/round-0000/raw/cond-plasma-cell-neoplasms-000.json
source file sha256
2314ce01316b2d7044d298c6d25eda12e99cc5f44273bc75efed6cd5e03a8c14
source json pointer
/studies/184/protocolSection/identificationModule/nctId
source kind
ctgov_condition_query
source record id
Source null
source string basis
parsed_JSON_string_unmodified
source string sha256
f706d213ab20bb78bc3962edbd1b352e2420bfe2ed2ad414ecd231f987484463
source url
https://clinicaltrials.gov/api/v2/studies?query.cond=Plasma+Cell+Neoplasms&filter.advanced=AREA%5BHasResults%5Dtrue&pageSize=1000&format=json&countTotal=true

Preserved source evidence · Not medical advice