Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 65 of 374 for:    LENALIDOMIDE AND Dexamethasone

A Phase 2, Open-Label, Multicenter Study of Ixazomib Plus Lenalidomide and Dexamethasone in Adult Japanese Patients With Relapsed and/or Refractory Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02917941
Recruitment Status : Completed
First Posted : September 28, 2016
Last Update Posted : September 27, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda

Brief Summary:
The purpose of this study is to evaluate the efficacy and safety of ixazomib plus lenalidomide and dexamethasone in Japanese patients with relapsed and/or refractory multiple myeloma.

Condition or disease Intervention/treatment Phase
Relapsed and/or Refractory Multiple Myeloma Drug: Ixazomib Drug: Lenalidomide Drug: Dexamethasone Phase 2

Detailed Description:

This is a phase 2, open label, single arm, multicenter study to evaluate the efficacy and safety of ixazomib plus lenalidomide and dexamethasone in Japanese patients with relapsed and/or refractory multiple myeloma (MM). The patient population will consist of adult men and women who have a confirmed diagnosis of MM, who have received 1 to 3 prior lines of therapy, and who meet other outlined eligibility criteria. Patients will receive study drug (ixazomib 4.0 mg) on Days 1, 8, and 15 plus lenalidomide (25 mg) on Days 1 through 21 and dexamethasone (40 mg) on Days 1, 8, 15, and 22 of a 28-day cycle. Patients may continue to receive treatment until progressive disease (PD) or unacceptable toxicity, whichever comes first. Dose modifications may be made based on toxicities. Patients with a low creatinine clearance < 60 mL/min will receive a reduced lenalidomide dose of 10 mg once daily on Days 1 through 21 of a 28-day cycle. The lenalidomide dose may be escalated to 15 mg once daily after 2 cycles if the patient is not responding to treatment and is tolerating the treatment. If renal function normalizes (ie, creatinine clearance >= 60 mL/min) and the patient continues to tolerate this treatment, lenalidomide may then be escalated to 25 mg once daily.

Treatment periods will be defined as 28-day cycles. Patients will be seen at regular treatment cycle intervals while they are participating in the study: four times a treatment cycle for the first 2 cycles, twice a treatment cycle for the 3rd cycle, and then once a treatment cycle for the remainder of their participation in the active treatment and, if applicable, the PFS and OS follow-up phases of the study.

Response will be assessed by investigator according to the International Myeloma Working Group criteria for all patients every 4 weeks until PD. Central laboratory data will be used for serum M-protein, urine M-protein and serum free light chain. All patients will be followed for survival after progression. Patients will be contacted every 12 weeks until death or termination of the study by the sponsor.

The study will be closed at 24 months from the enrollment of the last patient.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Open-Label, Multicenter Study of Ixazomib Plus Lenalidomide and Dexamethasone in Adult Japanese Patients With Relapsed and/or Refractory Multiple Myeloma
Actual Study Start Date : October 31, 2016
Actual Primary Completion Date : August 31, 2019
Actual Study Completion Date : August 31, 2019


Arm Intervention/treatment
Experimental: Ixazomib 4.0 mg, lenalidomide 25 mg, dexamethasone 40 mg
Patients will receive study drug (ixazomib 4.0 mg) on Days 1, 8, and 15 plus lenalidomide (25 mg) on Days 1 through 21 and dexamethasone (40 mg) on Days 1, 8, 15, and 22 of a 28-day cycle.
Drug: Ixazomib
Ixazomib capsules

Drug: Lenalidomide
Lenalidomide capsules

Drug: Dexamethasone
Dexamethasone Tablets




Primary Outcome Measures :
  1. Percentage of Participants With Very Good Partial Response (VGPR) or Better Response (Complete Response (CR) + VGPR) [ Time Frame: Up to 30 Months as a maximum; Participants may remain on treatment until the occurrence of progressive disease (PD) or unacceptable toxicity. The maximum treatment period will be 24 months after the last patient is enrolled. ]
    Response will be assessed using International Myeloma Working Group (IMWG) Criteria. CR is defined as negative immunofixation on the serum and urine and; disappearance of any soft tissue plasmacytomas and; < 5% plasma cells in bone marrow. VGPR is defined as Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours.


Secondary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: Up to 30 Months as a maximum; Participants may remain on treatment until the occurrence of PD or unacceptable toxicity. The maximum treatment period will be 24 months after the last patient is enrolled. ]
    PFS is defined as the time from the date of first study drug administration to the date of first documentation of PD or death from any cause, whichever occurs first.

  2. Overall Response Rate (ORR) [ Time Frame: Up to 30 Months as a maximum; Participants may remain on treatment until the occurrence of PD or unacceptable toxicity. The maximum treatment period will be 24 months after the last patient is enrolled. ]
    ORR is defined as the percentage of participants with Complete Response (CR) including stringent complete response (sCR), very good partial response (VGPR) and Partial Response (PR) assessed by the IRC using IMWG criteria.

  3. Duration of Response (DOR) [ Time Frame: Up to 30 Months as a maximum; Participants may remain on treatment until the occurrence of PD or unacceptable toxicity. The maximum treatment period will be 24 months after the last patient is enrolled. ]
    DOR will be measured as the time in months from the date of first documentation of a confirmed response of PR or better (CR [including sCR] + PR+ VGPR) to the date of the first documented PD among participants who responded to the treatment. Response was assessed by the investigator using IMWG Criteria.

  4. Time to Progression (TTP) [ Time Frame: Up to 30 Months as a maximum; Participants may remain on treatment until the occurrence of PD or unacceptable toxicity. The maximum treatment period will be 24 months after the last patient is enrolled. ]
    TTP will be measured as the time in months from the first dose of study treatment to the date of the first documented progressive disease (PD) as assessed using IMWG criteria.

  5. Number of participants reporting one or more treatment-emergent adverse events [ Time Frame: Up to 30 Months as a maximum; Participants may remain on treatment until the occurrence of PD or unacceptable toxicity. The maximum treatment period will be 24 months after the last patient is enrolled. ]
  6. Percentage of Participants With Markedly Abnormal Safety Laboratory Tests at Least Once Post-dose [ Time Frame: Up to 30 Months as a maximum; Participants may remain on treatment until the occurrence of PD or unacceptable toxicity. The maximum treatment period will be 24 months after the last patient is enrolled. ]
  7. Percentage of Participants With Markedly Abnormal Vital Sign Measurements at Least Once Post-dose [ Time Frame: Up to 30 Months as a maximum; Participants may remain on treatment until the occurrence of PD or unacceptable toxicity. The maximum treatment period will be 24 months after the last patient is enrolled. ]
  8. Overall Survival (OS) [ Time Frame: At the time of screening; Day 1 of each cycle; every 4 weeks until disease progression and thereafter every 12 weeks until death or study termination up to 30 Months as a maximum ]
    OS is defined as the time from the date of first study drug administration to the date of death.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female Japanese participants 20 years of age or older.
  2. Multiple myeloma diagnosed according to standard criteria either currently or at the time of initial diagnosis. The initial diagnosis must be symptomatic MM, although the relapsed disease does not need to be symptomatic.
  3. Participants must have measurable disease defined by at least 1 of the following 3 measurements based on central laboratory data: - Serum M-protein: >=1 g/dL (>= 10 g/L). - Urine M-protein: >=200 mg/24 hours. - Serum free light chain assay: involved free light chain level >=10 mg/dL (>= 100 mg/L), provided that the serum free light chain ratio is abnormal.
  4. Participants with RRMM who have received 1 to 3 prior therapies.

    This participant population includes the following 3 categories of participants:

    • Participants who relapsed from their therapy(s) but were not refractory to any previous therapy.
    • Participants who were refractory to all lines of previous therapy(s) (ie, participants who have never responded to any therapies received).
    • Participants who were relapsed from at least 1 line of therapy AND additionally were refractory to at least 1 line of therapy. For the purposes of this study, refractory MM is defined as PD on therapy or PD within 60 days after the last dose of a given therapy.

    A line of therapy is defined as 1 or more cycles of a planned treatment program. This may consist of 1 or more planned cycles of single-agent therapy or combination therapy, as well as a sequence of treatments administered in a planned manner. For example, a planned treatment approach of induction therapy followed by autologous stem cell transplantation, followed by maintenance is considered 1 line of therapy. Autologous and allogenic transplants are permitted.

  5. Participants must meet the following clinical laboratory criteria:

    • Absolute neutrophil count (ANC) >= 1,000/mm3, hemoglobin >= 8 g/dL and platelet count >= 75,000/mm3. Platelet transfusions to help participants meet eligibility criteria are not allowed within 3 days prior to screening.
    • Total bilirubin =< 1.5 x the upper limit of the normal range (ULN).
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN.
    • Calculated creatinine clearance >= 30 mL/min.
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  7. Participants who received prior allogenic transplant must have no active graft-versus-host disease (GVHD).
  8. Participants who meet the following conditions:

    Female participants who:

    • Are postmenopausal for at least 24 months before the screening visit, OR
    • Are surgically sterile, OR - Females of childbearing potential must:

      1. Have a negative pregnancy test with a sensitivity of at least 25 mIU/mL within 10 to 14 days and again within 24 hours prior to starting Cycle 1 of lenalidomide
      2. Agree to practice true abstinence or to begin TWO reliable methods of birth control (1 highly effective method and 1 additional effective method AT THE SAME TIME) for at least 28 days before starting study treatment through 90 days after the last dose of study treatment.
      3. Agree to ongoing pregnancy testing
      4. Adhere to the guidelines of the RevMate program Male participants, even if surgically sterilized (ie, status postvasectomy), must:
    • Agree to avoid sexual intercourse completely 90 days after the last dose of study treatment.
    • Agree to practice true abstinence or to practice effective barrier contraception during the entire study treatment period and 90 days after the last dose of study treatment if their partner is of childbearing potential, even if they have had a successful vasectomy, and
    • Adhere to the guidelines of the RevMate program
  9. Thromboembolism prophylaxis is required based on published standard or institutional standard of care.
  10. 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 participant at any time without prejudice to future medical care.
  11. Participant is willing and able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

  1. Participants who were refractory to lenalidomide or proteasome inhibitor-based therapy at any line. Refractory disease is defined as PD on treatment or PD within 60 days after the last dose of a given therapy. Participants who progressed the disease after 60 days from the last dose of a given therapy will be considered relapsed and are eligible for inclusion in the study. Participants who were refractory to thalidomide-based therapy are eligible.
  2. Female participants who are breast feeding or pregnant.
  3. Failure to have fully recovered (ie, =< Grade 1 toxicity) from the effects of prior chemotherapy (except for hair loss) regardless of the interval since last treatment.
  4. Major surgery within 14 days before enrollment.
  5. Radiotherapy within 14 days before enrollment.
  6. Central nervous system involvement.
  7. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before enrollment.
  8. Rash or pruritus requiring systemic medication within 14 days before enrollment.
  9. Diagnosis of Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
  10. 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 before enrollment.
  11. Systemic treatment with strong CYP3A inducers (rifampicin, carbamazepine, phenytoin), or St. John's wort within 14 days before enrollment.
  12. Ongoing or active systemic infection, known human immunodeficiency virus (HIV)- positive, known hepatitis B surface antigen seropositive or known hepatitis C virus (HCV)-RNA positive.

    Participants who have positive hepatitis B core antibody (HBcAb) can be enrolled but must have hepatitis B virus (HBV)-DNA negative. Participants who have positive hepatitis C antibody can be enrolled but must have HCV-RNA negative.

  13. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the participant inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens (eg, peripheral neuropathy that is Grade 1 with pain or Grade 2 or higher of any cause).
  14. Psychiatric illness/social situation that would limit compliance with study requirements.
  15. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
  16. Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements, or gastrointestinal condition that could interfere with the oral absorption or tolerance of treatment.
  17. Diagnosed or treated for another malignancy within 2 years before enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
  18. Participants who have participated in the previous clinical trial of ixazomib, or have been treated with ixazomib.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02917941


Locations
Layout table for location information
Japan
Nagoya, Aichi, Japan
Narita, Chiba, Japan
Shibukawa, Gunma, Japan
Fukuyama, Hiroshima, Japan
Kobe, Hyogo, Japan
Sagamihara, Kanagawa, Japan
Sendai, Miyagi, Japan
Ikoma, Nara, Japan
Sunto-gun, Shizuoka, Japan
Utsunomiya, Tochigi, Japan
Bunkyo-ku, Tokyo, Japan
Koto-ku, Tokyo, Japan
Shibuya-ku, Tokyo, Japan
Shinjuku-ku, Tokyo, Japan
Tachikawa, Tokyo, Japan
Chiba, Japan
Fukuoka, Japan
Ibaragi, Japan
Niigata, Japan
Okayama, Japan
Osaka, Japan
Sponsors and Collaborators
Takeda
Investigators
Layout table for investigator information
Study Director: Study Director Takeda

Layout table for additonal information
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02917941     History of Changes
Other Study ID Numbers: C16028
U1111-1187-4027 ( Other Identifier: Universal trial number )
JapicCTI-163381 ( Registry Identifier: JapicCTI )
First Posted: September 28, 2016    Key Record Dates
Last Update Posted: September 27, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Dexamethasone
Dexamethasone acetate
Lenalidomide
BB 1101
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Ixazomib
Glycine
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal