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Multiple MyelomaPhase 2NCT02891811

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

A Phase 2 study testing Carfilzomib, Thalidomide and Lenalidomide in people with Multiple Myeloma, run by Arbeitsgemeinschaft medikamentoese Tumortherapie at 21 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Carfilzomib, Thalidomide and Lenalidomide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
124 participants
Where
21 sitesin 2 countries
Study dates
10 Mar 2017to 28 Mar 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 18Show fewer
  • 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
  • Patients at cardiac risk (NYHA >II or pre-existing coronary heart disease or any other relevant cardiac complication) should be scheduled for a baseline echocardiography (ECHO) and can only be included if the left ventricular ejection fraction (LVEF) is ≥40%); independent of cardiac risk ECG has to be done for inclusion of Asian patients and patients > 75 years of age
  • 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
  • Females of childbearing potential (FCBP) must have a confirmed negative serum pregnancy test within the 21 days prior to randomization (performed at a central laboratory).
  • Females of childbearing potential and male subjects who are sexually active with FCBP must agree to use effective concomitant method(s) of contraception during the study and for 30 days (women) and 90 days (men) following the last study drug treatment administration.

Who cannot join

  • 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
Show all 32Show fewer
  • 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
  • Immunotherapy within the 21 days prior to randomization
  • Glucocorticoid therapy within the 14 days prior to randomization that exceeds accumulative dose of 160 mg dexamethasone or 1000 mg prednisone
  • Extended field radio therapy (more than 3 fields) within the 21 days prior to randomization
  • Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib) or any other component of formulation
  • Contraindication to dexamethasone, thalidomide or lenalidomide or any of the required concomitant drugs, supportive treatments or antiviral drugs, also including contraindication or hypersensitivity to any other components of these drugs (eg. hereditary galactose intolerance, complete lactase deficiency or glucose-galactose malabsorbtion in case of excipient lactose)
  • Active congestive heart failure (New York Heart Association [NYHA] Class III or IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, acute diffuse infiltrative pulmonary disease, pericardial disease, or myocardial infarction within 4 months prior to enrollment
  • Active infection within the 14 days prior to randomization requiring systemic antibiotics and/or antiviral therapy
  • Pleural effusions requiring thoracentesis within the 14 days prior to randomization
  • Ascites requiring paracentesis within the 14 days prior to randomization
  • Uncontrolled hypertension or uncontrolled diabetes despite medication
  • Significant neuropathy (Grade 2 with pain or Grade 3 or higher) within the 14 days prior to randomization
  • Known cirrhosis
  • Known human immunodeficiency virus (HIV) seropositivity, hepatitis C infection, or hepatitis B infection: subjects with past hepatitis B virus (HBV) infection or resolved HBV infection defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen (HBc) antibody test are eligible; subjects positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
  • Participation in another interventional study within the 28 days prior to randomization
  • Major surgery (except kyphoplasty) within the 28 days prior to randomization
  • Female subjects who are pregnant or lactating
  • Any other clinically significant medical disease or social condition that, in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent, be compliant with study procedures, or provide accurate information.

Trial locations and contacts

21 sites in 2 countries.

21 sites in 2 countries

Austria19 sites

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

    Graz, A-8036

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

    Innsbruck, 6020

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

    Kufstein, 6330

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

    Leoben, A-8700

  • Ordensklinikum Linz - Barmherzige Schwestern Linz, Interne I

    Linz, A-4010

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

    Linz, A-4020

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

    Linz, A-4021

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

    Mitterweng, 3500

  • Landeskrankenhaus Rankweil, Interne E (Hämatologie u. Onkologie)

    Rankweil, 6830

  • PMU Salzburg

    Salzburg, 5020

  • Univ.-Klinikum St. Pölten, Innere Medizin 1

    Sankt Pölten, 3100

  • Pyhrn-Eisenwurzen Klinikum Steyr, Innere Medizin II Onkologie

    Steyr, A-4400

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

    Vienna, 1090

  • Hanusch-Krankenhaus

    Vienna, 1140

  • Sozialmedizinisches Zentrum Ost - Donauspital, 2. Medizinische Abteilung

    Vienna, 1220

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

    Vienna, A-1090

  • Wilhelminenspital

    Vienna, A-1160

  • Landesklinikum Wiener Neustadt, Abteilung Onkologie

    Wiener Neustadt, 2700

  • Krankenhaus Zams, Innere Medizin, Internistische Onkologie u. Hämatologie

    Zams, 6511

Other trials in Austria

Germany2 sites

  • UK Leipzig Medizinische Klinik und Poliklinik I

    Leipzig, 04103

  • UK Würzburg Medizinische Klinik und Poliklinik II

    Würzburg, 97080

Other trials in Germany

About this study

Official title: A Randomized Phase II, 2-armed Study in Transplant Ineligible (TI) Patients With Newly Diagnosed Multiple Myeloma (NDMM) Comparing Carfilzomib + Thalidomide + Dexamethasone (KTd) Versus Carfilzomib + Lenalidomide + Dexamethasone (KRd) Induction Therapy With Respect to Response Rates and Investigating a Carfilzomib (K) Monotherapy Maintenance Strategy

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.

Read the detailed description

Multiple myeloma, a clonal neoplastic proliferation of plasma cells, is the second most common hematologic malignancy and accounts for approximately 72,000 annual deaths worldwide. There are an estimated 11,000 deaths per year in the US and more than 19,000 deaths per year in Europe.

This study examines the efficacy of carfilzomib (K) in combination with thalidomide, an old, well established first line immunomodulatory imide drugs (IMiD) in newly diagnosed multiple myeloma versus K in combination with lenalidomide in 1st line. This trial will also evaluate the adherence to and the safety of a thalidomide containing triplet by using a non-neurotoxic proteasome inhibitor. Moreover, weekly dosing of carfilzomib addresses the need for a more convenient dosing schedule. Finally, yet importantly, this trial will assess the efficacy of a less cost intensive triplet and a strategy to keep lenalidomide as backup for later lines.. The second part of the study - after completing 9 cycles induction therapy with KTd or KRd - patients of both arms will be pooled and again randomized 1:1 stratified by induction therapy into two arms (K-monotherapy versus observation-only).

Keywords
newly diagnosed multiple myeloma, carfilzomib, thalidomide, lenalidomide, dexamethasone, transplant ineligible, induction therapy, maintenance, Study Group of Medical Tumour Therapy (AGMT)
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CarfilzomibDrug

    Also called Kyprolis

    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)

  • ThalidomideDrug

    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

  • LenalidomideDrug

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

  • DexamethasoneDrug

    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

Study groups in NCT02891811
Study groupRoleWhat they receive
Induction Arm AExperimentalCarfilzomib + Thalidomide + Dexamethasone (KTd) for 9 cycles (day 1-28) Followed by second randomisation: maintenance arm with carfilzomib monotherapy versus "observation only" arm
Receives: Drug: Carfilzomib; Drug: Thalidomide; Drug: Dexamethasone
Induction Arm BActive comparatorCarfilzomib + Lenalidomide + Dexamethasone (KRd) for 9 cycles (day 1-28) Followed by second randomisation: maintenance arm with carfilzomib monotherapy versus "observation only" arm
Receives: Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

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

Secondary outcomes (10)

  1. Feasibility of a carfilzomib monotherapy maintenance

    Feasibility of maintenance therapy with carfilzomib will be investigated in comparison with observation only strategy by observing treatment and visit compliance (listing withdrawals, treatment/visit delays and drug modifications).

    Measured: after 12 months of maintenance therapy or observation only

  2. Safety (adverse events) of a carfilzomib monotherapy maintenance

    Safety will be assessed by the type, incidence, severity (CTCAE v 4.0), and relatedness of adverse events (AEs) to treatment and by the descriptive analysis of laboratory parameters related to safety. Adverse events will be summarized by presenting the number and percentage (as appropriate) of patients having any adverse event by body system, type of adverse event, and maximum severity.

    Measured: after 12 months of maintenance therapy or observation only

  3. Overall response rate (efficacy) of a carfilzomib monotherapy maintenance

    After 12 months maintenance treatment or observation overall response rate (ORR, ratio of the number of patients with CR to partial response (PR) divided by the number of all patients evaluable for response) will be analyzed descriptively and compared using a chi^2 test without continuity correction. A one-sided 97.5% confidence interval for the difference in ORR will be calculated.

    Measured: after 12 months of maintenance therapy or observation only

  4. Response

    The updated IMWG response criteria will be applied for response evaluation in all patients; this also includes minimal residual disease (MRD) evaluation; thus, response rates will be assessed qualitatively and quantitatively; MRD testing will be performed in all patients achieving complete remission (CR) and in patients which are in a CR at the end of maintenance

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

  5. Overall survival (OS)

    To determine Overall Survival (OS) in patients with NDMM ineligible for transplantation receiving either KTd versus KRd induction therapy and sub-sequent being randomised either to maintenance arm with carfilzomib or to control only for a maximum period of 12 months.

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

  6. Progression free survival (PFS)

    Response rates will be assessed qualitatively and quantitatively (PR, VGPR, CR, sCR, MRD according to IMWG Rajkumar 2011)

    Measured: after 9 months induction therapy

  7. Safety and tolerability (adverse events) of induction and maintenance treatment

    Safety and tolerability of KTd and KRd followed by randomization to carfilzomib maintenance for a maximum period of 12 months or observation only will be assessed by the type, incidence, severity (CTCAE v 4.0), and relatedness of AEs to treatment and by the descriptive analysis of laboratory parameters related to safety. Adverse events will be summarized by presenting the number and percentage (as appropriate) of patients having any adverse event by body system, type of adverse event, and maximum severity.

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

  8. Changes in quality of life (QoL)

    Changes in quality of life will be analyzed by using the cancer patient-specific questionnaire EORTC-QLQ-C30. Measures will be calculated and analyzed descriptively, and compared between treatment groups using a Mann-Whitney U-test for unpaired observations.

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

  9. Changes in quality of life (QoL) using multiple myeloma specific questionnaire

    Changes in quality of life will be analyzed by using the multiple myeloma-specific questionnaire "EORTC-QLQ-MY20". Measures will be calculated and analyzed descriptively, and compared between treatment groups using a Mann-Whitney U-test for unpaired observations.

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

  10. Changes of general health status

    Changes in general health status will be analyzed by using the questionnaires "EQ-5D-5L". QoL measures will be calculated and analyzed descriptively, and compared between treatment groups using a Mann-Whitney U-test for unpaired observations.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Sep 2016 (estimated)
  2. Study start10 Mar 2017
  3. Primary completion28 Mar 2024
  4. Study completion28 Mar 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
124 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02891811
Sponsor's protocol ID
AGMT_MM-2
Other IDs
2016-000475-24, 2016
Status last verified
Mar 2024
First submitted
10 Aug 2016
Last updated
29 Mar 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Carfilzomib, Thalidomide and Lenalidomide in people with Multiple Myeloma, run by Arbeitsgemeinschaft medikamentoese Tumortherapie at 21 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in Austria, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Response Rates (time frame: 36 weeks after start of induction treatment (9 cycles, each cycle is 28 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02891811.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2024; AzTrials last refreshed its copy on 6 Nov 2026.

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