A Phase 3 Study Comparing Oral Ixazomib Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Relapsed and/or Refractory Multiple Myeloma

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase IIITreatment18 and overC16010
NCI-2013-00086, 2011-005496-17, CTR20130908, NCT01564537

Trial Description

Summary

The purpose of this phase 3, randomized, double-blind, multicenter study is to compare Oral

Ixazomib (MLN9708) plus Lenalidomide and Dexamethasone versus Placebo plus Lenalidomide and

Dexamethasone in adult patients with relapsed and/or refractory multiple myeloma.

Eligibility Criteria

Inclusion Criteria:

Inclusion Criteria:

1. Male or female patients 18 years of age or older.

2. Multiple myeloma diagnosed according to standard criteria either currently or at the

time of initial diagnosis NOTE: The initial diagnosis must be symptomatic MM,

although the relapsed disease does not need to be symptomatic.

3. Patients must have measurable disease defined by at least 1 of the following 3

measurements:

• 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. Patients with relapsed and/or refractory MM who have received 1 to 3 prior therapies.

NOTE: This patient population includes the following 3 categories of patients:

• Patients who relapsed from their previous treatment(s) but were not refractory to

any previous treatment.

• Patients who were refractory to all lines of previous treatment(s) (ie, patients

who have never responded to any therapies received).

• Patients who were relapsed from at least 1 previous treatment AND additionally were

refractory to at least 1 previous treatment. For the purposes of this study,

refractory disease is defined as disease progression on treatment or progression

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. Patients must meet the following clinical laboratory criteria:

• Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet count ≥75,000/mm3.

Platelet transfusions to help patients meet eligibility criteria are not allowed

within 3 days prior to randomization.

• Total bilirubin ≤1.5 times the upper limit of the normal range (ULN).

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 times

ULN.

Calculated creatinine clearance ≥ 30 mL/min NOTE: Patients with a low

creatinine clearance ≤ 60 mL/min (or ≤ 50 mL/min, according to local

label/practice) 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 or > 50 mL/min, according to local label/practice) and the

patient continues to tolerate this treatment, lenalidomide may then be escalated

to 25 mg once daily.

6. ECOG performance status of 0, 1, or 2.

7. Patients who received prior allogenic transplant must have no active

graft-versus-host disease (GVHD).

8. Female patients 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. Either agree

to practice true abstinence, when this is in line with the preferred and usual lifestyle

of the patient. (Periodic abstinence [eg, calendar, ovulation, symptothermal,

post-ovulation methods] and withdrawal are not acceptable methods of contraception.) OR

begin TWO reliable methods of birth control: 1 highly effective method and 1 additional

effective method AT THE SAME TIME, at least 28 days before starting study drug through 90

days after the last dose of study treatment 3. Agree to ongoing pregnancy testing 4.

Adhere to the guidelines of the RevAssist program (United States [US] participants),

RevAid program (Canadian participants), iAccess program (Australian participants), RevMate

program (Japanese participants) or The Lenalidomide Pregnancy Risk Minimisation Plan as

outlined in the Study Manual (all other

Exclusion Criteria:

Inclusion Criteria:

1. Male or female patients 18 years of age or older.

2. Multiple myeloma diagnosed according to standard criteria either currently or at the

time of initial diagnosis NOTE: The initial diagnosis must be symptomatic MM,

although the relapsed disease does not need to be symptomatic.

3. Patients must have measurable disease defined by at least 1 of the following 3

measurements:

• 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. Patients with relapsed and/or refractory MM who have received 1 to 3 prior therapies.

NOTE: This patient population includes the following 3 categories of patients:

• Patients who relapsed from their previous treatment(s) but were not refractory to

any previous treatment.

• Patients who were refractory to all lines of previous treatment(s) (ie, patients

who have never responded to any therapies received).

• Patients who were relapsed from at least 1 previous treatment AND additionally were

refractory to at least 1 previous treatment. For the purposes of this study,

refractory disease is defined as disease progression on treatment or progression

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. Patients must meet the following clinical laboratory criteria:

• Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet count ≥75,000/mm3.

Platelet transfusions to help patients meet eligibility criteria are not allowed

within 3 days prior to randomization.

• Total bilirubin ≤1.5 times the upper limit of the normal range (ULN).

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 times

ULN.

Calculated creatinine clearance ≥ 30 mL/min NOTE: Patients with a low

creatinine clearance ≤ 60 mL/min (or ≤ 50 mL/min, according to local

label/practice) 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 or > 50 mL/min, according to local label/practice) and the

patient continues to tolerate this treatment, lenalidomide may then be escalated

to 25 mg once daily.

6. ECOG performance status of 0, 1, or 2.

7. Patients who received prior allogenic transplant must have no active

graft-versus-host disease (GVHD).

8. Female patients 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. Either agree

to practice true abstinence, when this is in line with the preferred and usual lifestyle

of the patient. (Periodic abstinence [eg, calendar, ovulation, symptothermal,

post-ovulation methods] and withdrawal are not acceptable methods of contraception.) OR

begin TWO reliable methods of birth control: 1 highly effective method and 1 additional

effective method AT THE SAME TIME, at least 28 days before starting study drug through 90

days after the last dose of study treatment 3. Agree to ongoing pregnancy testing 4.

Adhere to the guidelines of the RevAssist program (United States [US] participants),

RevAid program (Canadian participants), iAccess program (Australian participants), RevMate

program (Japanese participants) or The Lenalidomide Pregnancy Risk Minimisation Plan as

outlined in the Study Manual (all other

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

Millennium Pharmaceuticals, Inc.

    Trial Sites

    U.S.A.

    Alabama
    Birmingham

    University of Alabama at Birmingham Cancer Center

    Kelly Nicole Godby
    Principal Investigator

    Massachusetts
    Boston

    Brigham and Women's Hospital

    Paul E. Richardson
    Principal Investigator

    Dana-Farber Cancer Institute

    Paul E. Richardson
    Principal Investigator

    Minnesota
    Rochester

    Mayo Clinic

    Shaji K. Kumar
    Principal Investigator

    New York
    New York

    Laura and Issac Perlmutter Cancer Center at NYU Langone

    Amitabha Mazumder
    Principal Investigator

    Washington
    Seattle

    Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    William I. Bensinger
    Principal Investigator

    Link to the current ClinicalTrials.gov record.
    NLM Identifer NCT01564537

    Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.