Fase II undersøgelse af IRD (Ixazomib, Lenalidomid, Dexamethason) efter autolog stamcelletransplantation efterfulgt af vedligeholdelse Ixazomib eller Lenalidomid for myelomatose
Et fase II-studie af IRD (Ixazomib, Lenalidomid og Dexamethason) til konsolideringsterapi efter autolog stamcelletransplantation efterfulgt af vedligeholdelse Ixazomib eller Lenalidomid til myelomatose
The purpose of this research study is to evaluate a treatment regimen called IRD which will be given to participants after their stem cell transplant in an effort to help prolong the amount of time the participants are disease-free after transplant. IRD is a three-drug regimen consisting of ixazomib, lenalidomide (also called Revlimid), and dexamethasone. After 4 cycles of IRD, the participants will be randomized to receive maintenance therapy either with ixazomib or lenalidomide.
Studieoversigt
Status
Status
Betingelser
Betingelser
Intervention / Behandling
Intervention / Behandling
Detaljeret beskrivelse
Based on the further need to improve progression-free survival and overall survival post-autologous stem cell transplantation (ASCT) for multiple myeloma and the benefits seen of consolidation/maintenance treatment with immunomodulatory drugs thalidomide and lenalidomide and the proteasome inhibitor bortezomib, the natural next step is to evaluate combination regimens of immunomodulatory drugs and proteasome inhibitors as consolidation/maintenance post-ASCT. The regimen consisting of ixazomib, lenalidomide, and dexamethasone (IRD) has been shown to have low toxicity, and the availability of an oral formulation of ixazomib allows for easier administration when compared to bortezomib.
In this study, following consolidation with IRD, patients will be randomized to maintenance therapy with lenalidomide or ixazomib in order to collect pilot data comparing the toxicity and efficacy of maintenance therapy with immunomodulatory drugs and proteasome inhibitors.
09/23/2019: Following interim analysis 3 performed in August 2019, patients who were still in screening or in the consolidation phase of the trial were allowed to proceed with the consolidation study treatment. Following completion of consolidation, all patients were enrolled into the lenalidomide arm with the exception of those who discontinued lenalidomide during the consolidation phase due to toxicity. Patients who discontinued lenalidomide were allowed to be enrolled into the ixazomib arm following approval from the site-specific principal investigator and study-wide principal investigator. For patients previously randomized to ixazomib maintenance and continuing treatment, the patient and the respective treating physician were allowed to determine if the patient should remain on ixazomib or transition to the lenalidomide arm. Patients who were previously on lenalidomide maintenance and transitioned onto ixazomib due to toxicity were allowed to continue ixazomib maintenance. Patients who were on lenalidomide maintenance were continued unaltered. Once patients transitioned out of maintenance (to either transition lenalidomide or transition ixazomib), the patients were only followed for safety.
09/30/2021: Following analysis 4 in 2021, the consensus agreement was to allow patients to continue ixazomib at the discretion of the treating physician and with patient consent after being informed of the trial data. Those that continued transition ixazomib were only followed for safety.
Undersøgelsestype
Undersøgelsestype
Tilmelding (Faktiske)
Tilmelding
Fase
Fase
- Fase 2
Kontakter og lokationer
Studiesteder
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California
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Duarte, California, Forenede Stater, 91010
- City of Hope
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San Francisco, California, Forenede Stater, 94143
- University of California, San Francisco
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Colorado
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Denver, Colorado, Forenede Stater, 80218
- Colorado Blood Cancer Institute
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Georgia
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Atlanta, Georgia, Forenede Stater, 30322
- Emory University - Winship Cancer Institute
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Michigan
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Detroit, Michigan, Forenede Stater, 48201
- Karmanos Cancer Institute
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Minnesota
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Rochester, Minnesota, Forenede Stater, 55905
- Mayo Clinic
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Missouri
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St Louis, Missouri, Forenede Stater, 62864
- Washington University School of Medicine
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New York
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New York, New York, Forenede Stater, 10029
- Icahn School of Medicine at Mount Sinai
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Ohio
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Columbus, Ohio, Forenede Stater, 43210
- Ohio State University Comprehensive Cancer Center
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Tennessee
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Nashville, Tennessee, Forenede Stater, 37203
- Tennessee Oncology, PLLC
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Deltagelseskriterier
Berettigelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria
Each patient must meet all of the following inclusion criteria to begin IRD Consolidation:
- Between the ages of 18 and 70 years of age (inclusive) at time of enrollment
- 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
- Confirmed diagnosis of symptomatic multiple myeloma. (Patients with multiple myeloma with secondary amyloidosis are eligible.)
- Received at least two cycles of any regimen as initial systemic therapy for multiple myeloma and are within 2-16 months of the first dose of initial therapy
- Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2
- Adequate organ function as defined below:
Absolute neutrophil count (ANC) >= 1,000 mm^3 Platelet count >= 75,000/mm^3; platelet transfusions to help patient meet eligibility criteria are not allowed within 7 days before study enrollment Total bilirubin <= 1.5 x upper limit of normal range (ULN) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=3 x ULN Calculated creatinine clearance >= 30 mL/min
- Women of childbearing potential must follow pregnancy testing requirements as outlined in the Revlimid REMS program material. This is defined as either committing to continued abstinence from heterosexual intercourse or beginning TWO acceptable methods of contraception (one highly effective method and one additional effective method AT THE SAME TIME) at least 28 days prior to the start of lenalidomide, for the duration of study participation, and for 28 days following the last dose of lenalidomide. Women of childbearing potential must also agree to ongoing pregnancy testing.
- Men must agree to use a latex condom during sexual contact with a woman of childbearing potential even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- All study participants must be registered into the mandatory Revlimind REMS program and be willing to comply with its requirements. Per standard Revlimid REMS program requirements, all physicians who prescribe lenalidomide for research subjects enrolled into this trial, must be registered in, and must comply with, all requirements of the Revlimid REMS program.
Exclusion Criteria
Patients meeting any of the following exclusion criteria are not to be enrolled in the study:
- Female patients who are lactating or have a positive serum pregnancy test during the screening period
- Evidence of MM disease progression any time prior to enrollment. Progression from smoldering/asymptomatic MM to symptomatic MM is not exclusionary.
- Tandem autologous transplantation
- History of plasma cell leukemia or MM CNS involvement
- Administration or planned administration of any other concomitant chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy which would be considered a treatment of multiple myeloma until Day +28 post-transplant through discontinuation from study. Patients may be on corticosteroids if they are being given for disorders other than multiple myeloma (e.g., adrenal insufficiency, rheumatoid arthritis, etc.)
- Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
- Prior organ transplant requiring immunosuppressive therapy
- Active hepatitis A, B or C virus infection, or known human immunodeficiency virus (HIV) positive
- Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
- Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib
- Concurrent hematologic or non-hematologic malignancy requiring treatment (other than multiple myeloma and secondary amyloidosis)
- Cardiac syncope, uncompensated NYHA Class 3 or 4 congestive heart failure, myocardial infarction within the previous six months, unstable angina pectoris, clinically significant repetitive ventricular arrhythmias despite antiarrhythmic treatment, severe orthostatic hypotension, or clinically important autonomic disease
- Grade >= 3 peripheral neuropathy, or Grade 2 with pain on clinical examination during the screening period
- Major surgery within 14 days prior to enrollment
- Infection requiring systemic antibiotic therapy or other serious infection within 14 days prior to enrollment
- Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days prior to enrollment and throughout the duration of this trial
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Sekventiel tildeling
- Maskning: Ingen (Åben etiket)
Antal våben
Våben og indgreb
Deltagergruppe / ArmDeltagergruppe / Arm |
Intervention / BehandlingIntervention / Behandling |
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Eksperimentel: Consolidation: Ixazomib, Lenalidomide, & Dexamethasone
Consolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, & dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 15 mg of lenalidomide will be administered on daily on Days 1-21. |
Andre navne:
Andre navne:
Andre navne:
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Eksperimentel: Maintenance Arm 1: Ixazomib
Ixazomib will be administered on Days 1, 8, and 15 of a 28-day cycle at a starting dose of 4 mg until patient progresses or experiences an unacceptable toxicity. |
Andre navne:
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Eksperimentel: Maintenance Arm 2: Lenalidomide
Lenalidomide will be administered daily continuously for a 28-day cycle at a starting dose of 10 mg. If lenalidomide is tolerated well (i.e. no dose modification required) during the first three cycles, lenalidomide dose will be increased to 15 mg daily and will continue until patient progresses or experiences an unacceptable toxicity. |
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Number of Participants With Improvement in Minimal Residual Disease (MRD)
Tidsramme: After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)
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For the purposes of this study, a patient will be considered as having minimal residual disease if a positive result (1x10E06) is obtained using the Adaptive Clonoseq MRD testing. |
After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)
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Sekundære resultatmål
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Rate for MRD-positiv til MRD-negativ konvertering mellem de to vedligeholdelsesarme
Tidsramme: Cyklus 13 Dag 1 af vedligeholdelsesbehandling (ca. dag 364 af vedligeholdelsesbehandling)
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Cyklus 13 Dag 1 af vedligeholdelsesbehandling (ca. dag 364 af vedligeholdelsesbehandling)
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MRD-negative Rate After ASCT
Tidsramme: Prior to beginning consolidation treatment (Day -28 to Day 0)
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For the purposes of this study, a patient will be considered as having minimal residual disease if a positive result (1x10E06) is obtained using the Adaptive Clonoseq MRD testing |
Prior to beginning consolidation treatment (Day -28 to Day 0)
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Toxicity of IRD Consolidation
Tidsramme: After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)
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For the purposes of this study, toxicity will be defined as inability to receive 4 cycles of IRD consolidation due to toxicity. |
After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)
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Response Rate of IRD Consolidation
Tidsramme: After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)
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For the purposes of this study, response rate is defined as the improvement in complete response rate. Response will be determined by the International Myeloma Working Group (IMWG) Uniform Response Criteria. |
After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)
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Progression-free Survival of IRD Consolidation
Tidsramme: Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)
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Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout. |
Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)
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Overall Survival of IRD Consolidation
Tidsramme: Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)
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Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout. |
Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)
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Compare Toxicity Between the Two Maintenance Arms
Tidsramme: 30 days after the completion of maintenance treatment (estimated to be Day 1125 of maintenance treatment)
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The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting. |
30 days after the completion of maintenance treatment (estimated to be Day 1125 of maintenance treatment)
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Compare Response Rate Between the Two Maintenance Arms
Tidsramme: Through completion of maintenance treatment (estimated to be day 1095 of maintenance treatment)
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Through completion of maintenance treatment (estimated to be day 1095 of maintenance treatment)
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Compare Progression-free Survival Between the Two Maintenance Arms
Tidsramme: Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)
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Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout. |
Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)
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Compare Overall Survival Between the Two Maintenance Arms
Tidsramme: Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)
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Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout. |
Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)
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Association of Progression-free Survival With MRD-negativity
Tidsramme: Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)
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Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout. |
Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)
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Association of Progression-free Survival With MRD-positivity
Tidsramme: Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)
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Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout. |
Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)
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Association of Overall Survival With MRD-negativity
Tidsramme: Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)
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Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout. |
Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)
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Association of Overall Survival With MRD-positivity
Tidsramme: Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)
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Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout. |
Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study)
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Samarbejdspartnere og efterforskere
Sponsor
Sponsor
Samarbejdspartnere
Samarbejdspartnere
Efterforskere
Efterforskere
- Ledende efterforsker: Ravi Vij, M.D., Washington University School of Medicine
Publikationer og nyttige links
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Studiestart
Primær færdiggørelse (Faktiske)
Primær færdiggørelse
Studieafslutning (Anslået)
Studieafslutning
Datoer for studieregistrering
Først indsendt
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først indsendt, der opfyldte QC-kriterier
Først opslået (Anslået)
Først opslået
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering sendt
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Karsygdomme
- Hjerte-kar-sygdomme
- Neoplasmer
- Sygdomme i immunsystemet
- Neoplasmer efter histologisk type
- Hæmatologiske sygdomme
- Lymfoproliferative lidelser
- Immunproliferative lidelser
- Neoplasmer, Plasmacelle
- Hæmostatiske lidelser
- Paraproteinæmier
- Blodproteinforstyrrelser
- Hæmoragiske lidelser
- Hemiske og lymfatiske sygdomme
- Myelomatose
- Svovlforbindelser
- Organiske kemikalier
- Heterocykliske forbindelser, 1-ring
- Heterocykliske forbindelser
- Heterocykliske forbindelser, 2-ring
- Heterocykliske forbindelser, smeltet ring
- Kulbrinter
- Kulbrinter, cyklisk
- Kulhydrater
- Carboxylsyrer
- Kulbrinter, aromatisk
- Polycykliske forbindelser
- Piperidiner
- Gravidier
- Graviditet
- Steroider
- SMUSED-RING-forbindelser
- Steroider, fluoreret
- Benzenderivater
- Sulfonsyrer
- Svovlsyrer
- Gravideretrioler
- Sukker
- Phthalimider
- Phthalinsyrer
- Syrer, carbocykliske
- Piperidones
- Isoindoler
- Benzenesulfonater
- Arylsulfonater
- Arylsulfonsyrer
- Hexoser
- Monosaccharider
- Lenalidomid
- Dexamethason
- Calciumdobesilat
- Glukose
- Ixazomib
Andre undersøgelses-id-numre
Andre undersøgelses-id-numre
- 201411060
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