Ixazomib in Combination With Thalidomide - Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma

NCT02410694 | Completed Phase 2 DMC

• 1 other identifier: AGMT_MM-1
• Study Type: interventional
• Target: 90
• Locations: 3 countries
• Sites: 17

Brief Summary

Overview of Study Design: This is an open phase II, single-arm, multi-center study to evaluate progression free survival in patients receiving ixazomib in combination with thalidomide and dexamethasone (ITD) followed by an ixazomib maintenance phase of a maximum period of 12 months. The patient population will consist of adult male and female patients with multiple myeloma (MM) with relapsed and/or refractory disease after at least one prior treatment line. In case of enrollment patients will receive ixazomib 4.0mg at days 1, 8, 15, thalidomide 100mg at days 1 to 28 (50mg in patients aged ≥75 years), and dexamethasone 40mg (20mg in patients aged ≥75 years) at days 1, 8, 15 of a 28-day treatment cycle. The proposed number of cycles is 8. Treatment will be discontinued in case of progressive disease or in case of no response after 4 cycles (≤ SD after 4 cycles). After discontinuation of therapy an end of treatment visit (EOT) will be performed within 14 days after the last dose of the last combination treatment cycle. After 8 cycles of ITD therapy, maintenance treatment with 4.0mg ixazomib (3.0mg in patients aged ≥ 75 years at first day of maintenance phase) on days 1, 8, 15 of 28-day cycles will be administered to patients with ≥ MR for a maximum period of 12 months. Patients who completed less than 8 cycles of ITD treatment do not qualify for maintenance phase. Follow-up visits will be performed in 3-monthly intervals until the last patient on ixazomib maintenance therapy has concluded or discontinued the maintenance phase. A safety analysis will be conducted after enrollment of the first 6 patients and completion of at least two cycles in every patient.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  start of combination therapy to progressive disease or death due to any cause whichever occurs first, up to 4.5 years

Secondary Outcomes (6)

• Overall Response Rate (ORR)

  best and first response since start of therapy, up to 4,5 years

• Overall Survival (OS)

  start of therapy to death, up to 4,5 years

• Renal Response in a subgroup of patients with baseline GFR 15-30ml/min

  start of therapy to best renal response, up to 4,5 years

• Determination of safety by reporting of adverse events

  start of therapy to end of study therapy (appr. 2 yrs)

• Assessment of prognostic values of risk factors at diagnosis incl. clinical assessment and cytogenetic abnormalities

  screening to end of study (appr. 2 yrs)

Study Arms (1)

Ixazomib-Thalidomide-Dexamethasone

EXPERIMENTAL

Combination therapy of: Ixazomib 4.0mg at days 1, 8, 15, Thalidomide 100mg at days 1 to 28 (50mg in patients aged ≥75 years), Dexamethasone 40mg (20mg in patients aged ≥75 years) at days 1, 8, 15 of a 28-day treatment cycle. After 8 cycles of ITD therapy, maintenance treatment with 4.0mg ixazomib (3.0mg in patients aged ≥ 75 years at first day of maintenance phase) on days 1, 8, 15 of 28-day cycles will be administered to patients with ≥ MR for a maximum period of 12 months.

Drug: Ixazomib; Drug: Thalidomide; Drug: Dexamethasone

Interventions

Ixazomib DRUG

Ixazomib-Thalidomide-Dexamethasone

Thalidomide DRUG

Ixazomib-Thalidomide-Dexamethasone

Dexamethasone DRUG

Ixazomib-Thalidomide-Dexamethasone

Eligibility Criteria

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

You may qualify if:

• Male or female patients 18 yrs or older.
• Voluntary written consent
• Patients in need of therapy with a diagnosis of relapsed or refractory multiple myeloma who had at least one prior treatment line
• Patients must have measurable disease defined by at least 1 of the following criteria:
• Serum M-protein ≥ 10g/l
• Urine M-protein ≥ 200mg/24h
• Serum free light chain assay: involved serum light chain ≥ 10mg/dl provided that free light chain ration is abnormal
• Life expectancy \> 3 months
• ECOG (Eastern Cooperative Oncology Group) ≤ 2
• ANC ≥ 1.000/mm3 and platelet count ≥ 50.000/mm3
• Total bilirubin ≤ 2 x ULN
• ALT and AST ≤ 3 x ULN
• GFR ≥ 15ml/min as calculated by cockroft-Gault equation
• Female patients who:
• Are older than 50 years and postmenopausal for at least 1 year before the screening visit, OR

You may not qualify if:

• lactating females or have a positive serum pregnancy test
• Failure to have fully recovered (i.e., ≤ Grade 1 toxicity) from the reversible effects of prior chemotherapy
• Previous treatment with ixazomib
• Previous treatment with bortezomib or thalidomide within the last 3 months prior to baseline visit
• Primary refractory to, or relapsing during, or within ≤ 6 weeks after end of treatment with a proteasome inhibitor and/or thalidomide
• Previous anti-cancer treatment within the last 21 days prior to baseline visit (cycle 1 / day 1), except corticosteroid therapy (40 - 160mg dexamethasone or corticosteroid dose equivalent per month)
• Major surgery within 14 days before enrollment
• Radiotherapy within 14 days before enrollment. If the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib.
• Central nervous system involvement
• Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment
• Evidence of current uncontrolled cardiovascular conditions
• Systemic treatment, within 14 days before the first dose of ixazomib, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), 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
• Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive
• Any serious medical or psychiatric illness that could, in the investigator's opinion, 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

Sponsors & Collaborators

• Arbeitsgemeinschaft medikamentoese Tumortherapie: lead

Study Sites (17)

Medizinische Universitätsklinik Graz, Klinische Abteilung für Hämatologie

Graz, Styria, 8036, Austria

Location

UK Innsbruck, Universitätsklinik für Innere Medizin, Klinische Abteilung für Hämatologie und Onkologie

Innsbruck, Tyrol, 6020, Austria

Location

A.ö. BK Kufstein, Abteilung für Innere Medizin

Kufstein, Tyrol, 6330, Austria

Location

Ordensklinikum, KH der Barmherzigen Schwestern Linz, Interne I: Internistische Onkologie, Hämatologie und Gastroenterologie

Linz, Upper Austria, 4010, Austria

Location

KH der Elisabethinen Linz, 1. Interne Abteilung

Linz, Upper Austria, 4020, Austria

Location

Klinikum Wels-Grieskirchen, IV. Interne Abteilung

Wels, Upper Austria, 4600, Austria

Location

LKH Feldkirch, Interne E

Feldkirch, Vorarlberg, 6830, Austria

Location

Kepler Universitätsklinikum Linz, Innere Medizin 3, Zentrum für Hämatologie und medizinische Onkologie

Linz, 4021, Austria

Location

Universitätsklinik der PMU Universitätsklinik für Innere Medizin III

Salzburg, 5020, Austria

Location

KH der Barmherzigen Brüder Wien, Innere Medizin

Vienna, 1020, Austria

Location

Med. Universität Wien, Universitätsklinik f. Innere Medizin I, Klin. Abt. f. Hämatologie u. Hämostaseologie

Vienna, 1090, Austria

Location

Wilhelminenspital

Vienna, A-1160, Austria

Location

Faculty Hospital Brno and Faculty of Medicine MU Brno 2nd Internal Clinic

Brno, 639 00, Czechia

Location

Fakultní nemocnice Ostrava

Ostrava-Poruba, 708 52, Czechia

Location

Universitätsklinikum Leipzig - AöR Selbstständige Abteilung für Hämatologie, Internistische Onkologie und Hämostaseologie

Leipzig, 04103, Germany

Location

Universitätsklinikum Tübingen, Innere Medizin II

Tübingen, 72076, Germany

Location

Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II Zentrum Innere Medizin

Würzburg, 97080, Germany

Location

Related Publications (1)

• Ludwig H, Poenisch W, Knop S, Egle A, Schreder M, Lechner D, Hajek R, Gunsilius E, Krenosz KJ, Petzer A, Weisel K, Niederwieser D, Einsele H, Willenbacher W, Melchardt T, Greil R, Zojer N. Ixazomib-Thalidomide-Dexamethasone for induction therapy followed by Ixazomib maintenance treatment in patients with relapsed/refractory multiple myeloma. Br J Cancer. 2019 Oct;121(9):751-757. doi: 10.1038/s41416-019-0581-8. Epub 2019 Sep 27.

  PMID: 31558804 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ixazomib; Thalidomide; Dexamethasone

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)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Heinz Ludwig, MD

  Wilhelminenspital Vienna

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2015
• First Posted: April 8, 2015
• Study Start: April 1, 2015
• Primary Completion: March 28, 2019
• Study Completion: May 2, 2019
• Last Updated: December 13, 2019

Record last verified: 2019-12

Locations

DE (3); AU (12); CZ (2)