Patients With Newly Diagnosed Multiple Myeloma Comparing KTd vs. KRd Induction Therapy and Investigating a K-mono Maintenance Strategy

NCT02891811 | Completed Phase 2

• 2 other identifiers: AGMT_MM-22016-000475-24
• Study Type: interventional
• Target: 124
• Locations: 2 countries
• Sites: 21

Brief Summary

This is a randomized, 2-arm phase II, multi-center study to evaluate the overall response rate in newly diagnosed, transplant ineligible patients receiving 9 cycles induction therapy with either KTd or KRd followed by randomization to either carfilzomib maintenance treatment for 12 months or to observation only. Maintenance is given for 12 cycles or progression of disease, whatever occurs first.

Conditions

Multiple Myeloma

Keywords

newly diagnosed multiple myeloma; carfilzomib; thalidomide; lenalidomide; dexamethasone; transplant ineligible; induction therapy; maintenance; Study Group of Medical Tumour Therapy (AGMT)

Outcome Measures

Primary Outcomes (1)

• Response Rates

  Overall response rate (ORR) will be assessed according to International Myeloma Working Group (IMWG) criteria to determine the ORR in patients NDMM after receiving 9 cycles induction therapy with either carfilzomib in combination with thalidomide and dexamethasone or carfilzomib in combination with lenalidomide and dexamethasone

  36 weeks after start of induction treatment (9 cycles, each cycle is 28 days)

Secondary Outcomes (10)

• Feasibility of a carfilzomib monotherapy maintenance

  after 12 months of maintenance therapy or observation only

• Safety (adverse events) of a carfilzomib monotherapy maintenance

  after 12 months of maintenance therapy or observation only

• Overall response rate (efficacy) of a carfilzomib monotherapy maintenance

  after 12 months of maintenance therapy or observation only

• Response

  after 21 months (9 months induction therapy and 12 months maintenance)

• Overall survival (OS)

  after 21 months (9 months induction therapy and 12 months maintenance)

Study Arms (2)

Induction Arm A

EXPERIMENTAL

Carfilzomib + Thalidomide + Dexamethasone (KTd) for 9 cycles (day 1-28) Followed by second randomisation: maintenance arm with carfilzomib monotherapy versus "observation only" arm

Drug: Carfilzomib; Drug: Thalidomide; Drug: Dexamethasone

Induction Arm B

ACTIVE COMPARATOR

Carfilzomib + Lenalidomide + Dexamethasone (KRd) for 9 cycles (day 1-28) Followed by second randomisation: maintenance arm with carfilzomib monotherapy versus "observation only" arm

Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Carfilzomib DRUG

Induction treatment: Cycle 1 day 1+2: 20 mg/m2; days 8,9, 15 and 16: 27 mg/m2; Cycle 2: 27 mg/m2 on days 1,2,8,9,15 and 16; Cycle 3-9: 56 mg/m2 on days 1, 8 and 15; IV duration: 30-60 minutes; Maintenance treatment with carfilzomib (last tolerated dose on day 1 and 15 (± 7 days) of each cycle)

Also known as: Kyprolis

Induction Arm A; Induction Arm B

Thalidomide DRUG

100mg orally on days 1-28 in patients \<75 years of age at Cycle 1; 50mg p.o. on days 1-28 in patients ≥ 75 years of age at Cycle 1

Induction Arm A

Lenalidomide DRUG

25mg p.o. on days 1-21 of each cycle

Induction Arm B

Dexamethasone DRUG

40mg p.o. on days 1, 8, 15,22 (± 1 day ) in patients \<75 years of age at Cycle 1; 20mg p.o. on days 1, 8, 15, 22 (± 1 day) in patients ≥ 75 years of age at Cycle 1, given 4 hours-30 min prior to carfilzomib

Induction Arm A; Induction Arm B

Eligibility Criteria

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

You may qualify if:

• Able to provide written informed consent in accordance with federal, local, and institutional guidelines
• newly diagnosed, symptomatic multiple myeloma
• Transplant-ineligibility: age \> 65 years or patients not eligible due to comorbidities determined by investigator or patients not willing to undergo autologous stem-cell transplantation (ASCT) on personal preference
• Measurable disease, as defined by one or more of the following (assessed within 21 days prior to randomization):
• Serum M-protein ≥ 0.5 g/dL, or
• Urine M-protein ≥ 200 mg/24 hours, or
• In subjects without detectable serum or urine M-protein, serum-free light chain (SFLC) \> 100 mg/L (involved light chain) and an abnormal κ/λ ratio
• No prior treatment for multiple myeloma
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1
• Adequate organ and bone marrow function within the 21 days prior to randomization defined by:
• Bilirubin \< 2 times the upper limit of normal (ULN), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 times the ULN
• growth factor support for max 3 days allowed to achieve an absolute neutrophil count (ANC) ≥ 1000/mm3 (screening ANC should be of required)
• Hemoglobin ≥ 7.0 g/dL; use of erythropoietic stimulating factors and red blood cell (RBC) transfusion per institutional guidelines is allowed, however the most recent RBC transfusion may not have been done within 7 days prior to obtaining screening hemoglobin.
• Platelet count ≥ 30,000/mm3
• Calculated or measured creatinine clearance (CrCl) of ≥ 30 mL/min. Calculation should be based on the Cockcroft and Gault formula: \[(140 - Age) ∙ Mass (kg) / (72 ∙ Creatinine mg/dL)\]; multiply result by 0.85 if female

You may not qualify if:

• ECOG ≥2
• Frail patients
• Waldenström macroglobulinemia
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Plasma cell leukemia (\> 2.0 × 109/L circulating plasma cells by standard differential)
• Myelodysplastic syndrome
• Smoldering myeloma and monoclonal gammopathy of undetermined significance (MGUS)
• Second malignancy within the past 5 years except:
• Adequately treated basal cell or squamous cell skin cancer
• Carcinoma in situ of the cervix
• Prostate cancer ≤ Gleason score 6 with stable prostate-specific antigen (PSA over 12 months
• Ductal breast carcinoma in situ with full surgical resection (i.e., negative margins)
• Treated medullary or papillary thyroid cancer
• Similar condition with an expectation of \> 95% five-year disease-free survival
• History of or current amyloidosis

Sponsors & Collaborators

• Arbeitsgemeinschaft medikamentoese Tumortherapie: lead
• Amgen: collaborator

Study Sites (21)

Medizinische Universitaet Graz, Univ.-Klinik f. Innere Medizin, Onkologie

Graz, A-8036, Austria

Location

Med. Universität Innsbruck, Univ.-Klinik f. Innere Medizin V, Hämatologie u. Onkologie

Innsbruck, 6020, Austria

Location

Bezirkskrankenhaus Kufstein, Innere Medizin, Interne II u. onkologische Tagesklinik

Kufstein, 6330, Austria

Location

LKH Hochsteiermark - Standort Leoben Abteilung für Innere Medizin und Hämatologie und internistische Onkologie

Leoben, A-8700, Austria

Location

Ordensklinikum Linz - Barmherzige Schwestern Linz, Interne I

Linz, A-4010, Austria

Location

Ordensklinikum Linz - Elisabethinen, I. Interne Abt. Haemato-Onkologie

Linz, A-4020, Austria

Location

Kepler Univ.-Klinikum Linz, Klinik f. Interne 3

Linz, A-4021, Austria

Location

Univ.Klinikum Krems, Klin. Abt. f. Innere Medizin 2

Mitterweng, 3500, Austria

Location

Landeskrankenhaus Rankweil, Interne E (Hämatologie u. Onkologie)

Rankweil, 6830, Austria

Location

PMU Salzburg

Salzburg, 5020, Austria

Location

Univ.-Klinikum St. Pölten, Innere Medizin 1

Sankt Pölten, 3100, Austria

Location

Pyhrn-Eisenwurzen Klinikum Steyr, Innere Medizin II Onkologie

Steyr, A-4400, Austria

Location

Medizinische Univ. Wien, Univ.Klinik f. Innere Medizin I, Onkologie

Vienna, 1090, Austria

Location

Hanusch-Krankenhaus

Vienna, 1140, Austria

Location

Sozialmedizinisches Zentrum Ost - Donauspital, 2. Medizinische Abteilung

Vienna, 1220, Austria

Location

Medizinische Univ. Wien, Univ.Klinik f. Innere Medizin I, Hämatologie u. Hämostaseologie

Vienna, A-1090, Austria

Location

Wilhelminenspital

Vienna, A-1160, Austria

Location

Landesklinikum Wiener Neustadt, Abteilung Onkologie

Wiener Neustadt, 2700, Austria

Location

Krankenhaus Zams, Innere Medizin, Internistische Onkologie u. Hämatologie

Zams, 6511, Austria

Location

UK Leipzig Medizinische Klinik und Poliklinik I

Leipzig, 04103, Germany

Location

UK Würzburg Medizinische Klinik und Poliklinik II

Würzburg, 97080, Germany

Location

Related Links

• Sponsor

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; Thalidomide; Lenalidomide; 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: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2016
• First Posted: September 8, 2016
• Study Start: March 10, 2017
• Primary Completion: March 28, 2024
• Study Completion: March 28, 2024
• Last Updated: March 29, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (19); DE (2)