Combination Chemotherapy and Donor Stem Cell Transplant Followed by Ixazomib Citrate Maintenance Therapy in Treating Patients With Relapsed High-Risk Multiple Myeloma
NCT ID: NCT02504359
Last Updated: 2020-11-23
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE1
11 participants
INTERVENTIONAL
2015-07-20
2020-09-09
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
I. Safety of BEAM (carmustine, cytarabine, etoposide, melphalan) allogeneic transplant within 100 days, defined as the day 100 transplant related mortality (TRM).
II. Safety of oral ixazomib maintenance therapy from day 100 post allogeneic transplant up to 2 years, defined by the incidence of grade III-IV acute (or overlap) graft-versus-host disease (GvHD) and grade III-IV ixazomib related toxicity.
OUTLINE:
BEAM CONDITIONING REGIMEN: Patients receive carmustine on day -6, cytarabine and etoposide on days -5 to -2, and melphalan on day -1.
PERIPHERAL BLOOD STEM CELL TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplantation on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus intravenously (IV) or orally (PO) on days -2 to at least 6 months with a taper as early as 3 months post-transplant and methotrexate IV on days 1, 3, 6, and 11.
MAINTENANCE THERAPY: Beginning between days 100 and 180 post-transplant, patients receive ixazomib PO on days 1 and 14 or days 1, 8, and 15 if the principal investigator deems it medically important. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days through 4 months post last dose of ixazomib.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Treatment (BEAM allogeneic transplant, ixazomib)
BEAM CONDITIONING REGIMEN: Patients receive carmustine on day -6, cytarabine and etoposide on days -5 to -2, and melphalan on day -1.
PERIPHERAL BLOOD STEM CELL TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplantation on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO on days -2 to at least 6 months with a taper as early as 3 months post-transplant and methotrexate IV on days 1, 3, 6, and 11.
MAINTENANCE THERAPY: Beginning between days 100 and 180 post-transplant, patients receive ixazomib PO on days 1 and 14 or days 1, 8, and 15 if the principal investigator deems it medically important. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic peripheral blood stem cell transplantation
Carmustine
Given BEAM chemotherapy
Cytarabine
Given BEAM chemotherapy
Etoposide
Given BEAM chemotherapy
Ixazomib Citrate
Given PO
Melphalan
Given BEAM chemotherapy
Methotrexate
Given IV
Peripheral Blood Stem Cell Transplantation
Undergo allogeneic peripheral blood stem cell transplantation
Quality-of-Life Assessment
Ancillary studies
Tacrolimus
Given IV or PO
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic peripheral blood stem cell transplantation
Carmustine
Given BEAM chemotherapy
Cytarabine
Given BEAM chemotherapy
Etoposide
Given BEAM chemotherapy
Ixazomib Citrate
Given PO
Melphalan
Given BEAM chemotherapy
Methotrexate
Given IV
Peripheral Blood Stem Cell Transplantation
Undergo allogeneic peripheral blood stem cell transplantation
Quality-of-Life Assessment
Ancillary studies
Tacrolimus
Given IV or PO
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* High-risk multiple myeloma defined by cytogenetic or fluorescence in situ hybridization (FISH) detection of any one or more of the following:
* Deletion 17p
* Translocation t(4;14)
* Translocation t(14;16)
* Translocation t(14;20)
* Chromosome 1q gain
* Chromosome 1p deletion
* Deletion 13q by conventional karyotyping (FISH only not acceptable)
* Hypodiploidy
* High-risk gene expression profiling (GEP) at the time of relapse
* Beta-2 (B2) microglobulin \> 5.5 mg
* Plasmablastic morphology (\> 2%)
* Relapsed plasma cell leukemia
* Chemo-sensitive disease; patients with relapsed plasma cell leukemia may have received systemic therapy including an autologous transplant but it is not required; patients with relapsed multiple myeloma (MM) must have received prior systemic therapy including an autologous transplant; patient must be in at least a PR at the time of transplant; early relapse from complete response will be allowed
* Measurable disease at the time of relapse, defined as a monoclonal immunoglobulin spike on serum electrophoresis of \>= 1 gm/dL (immunoglobulin \[IG\]G) or \>= 0.5 gm/dL (IGA) and/or urine monoclonal immunoglobulin spike of \> 200 mg/24 hours and/ or involved free light chain (FLC) level \>= 10 mg/dl and the serum FLC ratio is abnormal
* Non-secretors must have measurable disease such as plasmacytomas, or positron emission tomography (PET) avid lytic lesions or bone marrow plasmacytosis \>= 30% at the time of relapse to be eligible
* The patient must have an available sibling or matched unrelated donor with at least a 7/8 human leukocyte antigen (HLA) match
* Creatinine =\< 2.0 mg/dL
* Ejection fraction \>= 45%
* Diffusing capacity of the lungs for carbon monoxide (DLCO) \>= 50%
* Forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) \>= 50% predicted
* Both men and women and members of all races and ethnic groups will be included
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 50%)
* Willing to use adequate contraception for the duration of time on the study and for 90 days after the last therapy
* Female patients must meet one of the following:
* Postmenopausal for at least 1 year before the screening visit, OR
* Surgically sterile, OR
* If they are of childbearing potential:
* Agree to 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 90 days after the last dose of study drug, OR
* 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
* 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
* DONOR: HLA genotypically identical sibling matched relative
* DONOR: HLA matched unrelated donor according to Standard Practice HLA matching criteria:
* Matched HLA-A, -B, -C, and -DRB1 alleles by high resolution typing
* Only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing
Exclusion Criteria
* POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein \[protein\] and skin changes)
* Bilirubin \> 1.5 x the upper limit of normal
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \> 2.5 x the upper limit of normal
* Patients with \>= grade III or grade II with pain peripheral neuropathy (National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v.\] 4.03 criteria)
* Receiving steroids \> the equivalent of 10 mg prednisone daily for other medical conditions, e.g., asthma, systemic lupus erythematosus, rheumatoid arthritis
* Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment
* Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive
* 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
* Second malignancy requiring concurrent treatment or those with non-hematological malignancies (except non-melanoma skin cancers); cancer treated with curative intent \< 5 years previously will not be allowed unless approved by the protocol chair; cancer treated with curative intent \> 5 years previously is allowed
* Other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol
* Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
* Radiotherapy within 14 days before enrollment; if the involved field is limited to a single site, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib
* Systemic treatment, within 14 days before the first dose of ixazomib, with strong inhibitors of 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
* Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing
* Female patients who are lactating or have a positive serum pregnancy test during the screening period
* Failure to have fully recovered (i.e., =\< grade 1 toxicity) from the reversible effects of prior chemotherapy
* Major surgery within 14 days before enrollment
* Central nervous system involvement
* Participation in other clinical treatment trials, including those with other investigational agents not included in this trial, within 21 days of the start of this trial and throughout the duration of this trial
* DONOR: Identical twin
* DONOR: Donors unwilling to donate PBSC
* DONOR: Pregnancy
* DONOR: Infection with HIV
* DONOR: Inability to achieve adequate venous access
* DONOR: Known allergy to filgrastim (G-CSF)
* DONOR: Current serious systemic illness
* DONOR: Failure to meet institutional criteria for stem cell donation
* DONOR: Patient and donor pairs must not be homozygous at mismatched allele
18 Years
65 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Oregon Health and Science University
OTHER
OHSU Knight Cancer Institute
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Richard Maziarz
Principal Investigator
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Richard Maziarz, MD
Role: PRINCIPAL_INVESTIGATOR
OHSU Knight Cancer Institute
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Duke University Medical Center
Durham, North Carolina, United States
OHSU Knight Cancer Institute
Portland, Oregon, United States
Countries
Review the countries where the study has at least one active or historical site.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NCI-2015-01065
Identifier Type: REGISTRY
Identifier Source: secondary_id
HEM-14099-LM
Identifier Type: -
Identifier Source: secondary_id
IRB00011097
Identifier Type: OTHER
Identifier Source: secondary_id
IRB00011097
Identifier Type: -
Identifier Source: org_study_id