Pomalidomide and Dexamethasone With or Without Ixazomib in Treating Patients With Relapsed Multiple Myeloma

Overview

This randomized phase I/II trial studies the side effects and best dose of pomalidomide and ixazomib when given together with dexamethasone and to see how well pomalidomide and dexamethasone with or without ixazomib works in treating patients with multiple myeloma that has come back. Biological therapies, such as pomalidomide and dexamethasone, may stimulate the immune system in different ways and stop cancer cells from growing. Ixazomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether pomalidomide and dexamethasone are more effective with or without ixazomib in treating multiple myeloma.

SparkCures ID 472
Trial Phase Phase 1/2
Enrollment 73 Patients
Treatments
Trial Sponsors
  • Alliance for Clinical Trials in Oncology
Trial Collaborators
  • National Cancer Institute (NCI)
  • Celgene Corporation
  • Millennium Pharmaceuticals, Inc.
NCT Identifier

NCT02004275

Am I Eligible?

The following criteria is a partial list of reasons why patients may or may not be eligible to participate in this clinical trial. Further evaluation with a medical professional will be required to determine full eligibility.

The following criteria is provided for health care professionals.

  • Histologically confirmed diagnosis of symptomatic multiple myeloma; relapsed disease is myeloma that has previously responded to prior therapy (MR or better) and subsequently progressed
  • Patient must have measurable disease or non-measurable disease, defined as one or more of the following holding true:
    • Measurable disease:
      • Serum M-protein >= 1.0 g/dL (>= 0.5 g/dL for IgA or IgM myeloma) and/or
      • Urine M-protein >= 200 mg/24 hours and/or
      • Involved serum free light chain level >= 10 mg/dL AND an abnormal serum free light chain ratio
    • For non-measurable disease:
      • Baseline marrow burden of myeloma of at least 30%
  • Progression on lenalidomide as part of first line therapy (lenalidomide-refractory disease)

    * Lenalidomide-refractory disease is defined as disease progression on or progression within 60 days of the last dose of a lenalidomide-based treatment; patients should have received at least 2 cycles of a lenalidomide-based regimen to be evaluable for refractoriness; examples: 1) progression on lenalidomide maintenance therapy after initial induction +/- consolidation; 2) initial response followed by progression on continuous lenalidomide-dexamethasone +/- elotuzumab or daratumumab

  • Pomalidomide naive disease
  • Proteasome inhibitor naive or sensitive disease; proteasome inhibitor sensitive disease is defined as a PR or better to prior proteasome inhibitor-based therapy that is maintained for >= 60 days from the last dose of the proteasome inhibitor

    * A patient who receives induction therapy with lenalidomide, bortezomib and dexamethasone and achieves a PR or better but subsequently progresses on continued lenalidomide or lenalidomide-dexamethasone would be eligible provided the progression occurs 60 days or more after discontinuation of the bortezomib; similarly, ixazomib exposure is allowed provided they meet the definition of proteasome inhibitor sensitive disease

  • 1 prior line of systemic therapy for multiple myeloma, where a line of therapy for myeloma is defined as 1 or more planned cycles of single agent or combination therapy, as well as a planned series of treatment regimens administered in a sequential manner (e.g. lenalidomide, bortezomib and dexamethasone induction therapy for 4 cycles followed by autologous stem cell transplantation and then lenalidomide maintenance therapy would be considered 1 line of prior therapy); a new line of therapy begins when a planned therapy is modified to include other treatment agents (alone or in combination) as a result of disease progression, disease relapse or treatment-related toxicity (e.g. a patient is progressing in the face of lenalidomide maintenance therapy and has bortezomib and dexamethasone added into their regimen); a new line of therapy also begins when a planned treatment-free interval is interrupted by the need to start treatment due to disease relapse/progression (e.g. a patient with relapsed myeloma achieves a partial response after a planned 8 cycles of cyclophosphamide, bortezomib and dexamethasone, enjoys an 8-month period off therapy but then experiences disease progression requiring re-initiation of therapy)
  • Allogeneic stem cell transplantation is allowed provided the patient is >= 1 year from transplant at time of registration, is not on immunosuppressive therapy to treat/prevent graft-versus-host disease, has no evidence of active graft versus host disease, and no evidence of active infection
  • No other chemotherapy or radiation therapy within 14 days prior to registration
  • No investigational therapy within 14 days prior to registration
  • No major surgery within 28 days prior to registration
  • No G-CSF (filgrastim) or GM-CSF (sargramostim) within 7 days of registration or pegfilgrastim within 14 days of registration to meet eligibility criteria
  • No platelet transfusions within 7 days of registration to meet eligibility criteria; Note: red blood cell transfusions are allowed at any time
  • A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
    • Women of childbearing potential:
      • Must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mlU/ml no more than 14 days prior to registration and must agree to repeat this test within 24 hours of starting pomalidomide
      • Must either commit to complete abstinence from heterosexual contact or begin TWO acceptable methods of birth control, one highly effective method and one additional effective (barrier) method, AT THE SAME TIME, before starting pomalidomide
      • Must agree to ongoing pregnancy testing
      • Must agree to not become pregnant or breast feed a child during treatment on this protocol
    • Men must practice complete abstinence or agree to use a condom during sexual contact with a female of childbearing potential, even if they have had a successful vasectomy
    • Note: All participants must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Absolute neutrophil count (ANC) >= 1.0 x 10^9/L
  • Platelet count >= 50 x 10^9/L
  • Calculated (Calc.) creatinine clearance >= 30 mL/min; calculated utilizing the Cockcroft-Gault formula or 24-hour urine collection
  • Total bilirubin < 1.5 x upper limits of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x upper limits of normal (ULN)
  • Note: G-CSF and platelet transfusions cannot be used to increase counts to meet eligibility criteria
  • Patients cannot have:
    • Central nerve system involvement
    • Primary refractory multiple myeloma, where primary refractory multiple myeloma is defined as disease that is nonresponsive - patients who have never achieved a minimal response (MR) or better - with any therapy over the course of their disease; it includes patients who never achieve MR or better in whom there is no significant change in M-protein and no evidence of clinical progression as well as patients who meet criteria for true progressive disease (PD)
    • Primary or secondary plasma cell leukemia
    • Light-chain (AL) amyloidosis or polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome
    • Known active hepatitis C based on:
      • +hepatitis C virus (HCV) antibody (confirmed)
      • +HCV RNA
      • Liver disease with history of positive serology
      • Note: patients with a prior history of hepatitis C that has been successfully eradicated with antiviral therapy are eligible
    • Known hepatitis B surface antigen positivity
    • Previous hypersensitivity to any of the components of the study treatment
    • Prior history of erythema multiforme with thalidomide or lenalidomide treatment
  • =< grade 2 peripheral neuropathy
  • Adequate cardiac function, defined as:
    • No electrocardiogram (EKG) evidence of acute ischemia
    • No EKG evidence of active, clinically significant conduction system abnormalities
    • No EKG evidence of > grade 2 (> 480 ms) corrected QT (QTc) prolongation
    • Prior to study entry, any EKG abnormality at screening not felt to put the patient at risk has to be documented by the investigator as not medically significant
    • No uncontrolled angina or severe ventricular arrhythmias
    • No clinically significant pericardial disease
    • No history of myocardial infarction within 6 months prior to registration
    • No class 3 or higher New York Heart Association congestive heart failure
  • No strong inducers of cytochrome P450 (CYP) 3A4 or CYP1A2 or strong inhibitors of CYP3A4 or CYP1A2 within 14 days prior to registration
    • Note: Ixazomib is a substrate of CYP3A4 and CYP1A2
  • Patients with human immunodeficiency virus (HIV) infection are eligible, provided they meet the following:
    • No history of acquired immunodeficiency syndrome (AIDS)-defining conditions or other HIV related illness
    • Cluster of differentiation (CD)4+ cells nadirs > 350/mm^3 within 28 days prior to registration
    • Treatment sensitive HIV and, if on anti-HIV therapy, HIV viral load < 50 copies/mm^3 within 28 days prior to registration
    • Note: HIV+ patients who enroll on this study and are assigned to treatment with ixazomib may need to modify their anti-retroviral therapy prior to receiving protocol therapy if they are on strong inducers or potent inhibitors of cytochrome P450 3A4
  • RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Patients randomized to Arm 1 may opt to switch to the 3-drug regimen following disease progression; these patients must be re-registered to the study and meet the eligibility criteria below
  • RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Patient must have measurable disease or non-measurable disease after progression on pomalidomide + dexamethasone, defined as one or more of the following holding true:

    * Measurable disease:

    • Serum M-protein >= 0.5 g/dL and/or
    • Urine M-protein >= 200 mg/24 hours and/or
    • Involved serum free light chain level >= 10 mg/dL AND an abnormal serum free light chain ratio

      * For non-measurable disease:

    • Marrow burden of myeloma of at least 30%
  • RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2):

    • Women of childbearing potential:

      ** Must have a negative serum or urine pregnancy test within 72 hours prior to re-registration

      ** Must either commit to complete abstinence from heterosexual contact or begin TWO acceptable methods of birth control, one highly effective method and one additional effective (barrier) method, AT THE SAME TIME, before starting pomalidomide

      ** Must agree to ongoing pregnancy testing

      ** Must agree to not become pregnant or breast feed a child during treatment on this protocol

    • Men must practice complete abstinence or agree to use a condom during sexual contact with a female of childbearing potential, even if they have had a successful vasectomy
    • Note: All participants must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
  • RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): ECOG performance status 0-2
  • RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Absolute neutrophil count (ANC) >= 1.0 x 10^9/L
  • RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Platelet count >= 50 x 10^9/L
  • RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Calc. creatinine clearance >= 30 mL/min

    * Calculated utilizing the Cockcroft-Gault formula or 24-hour urine collection

  • RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Total bilirubin < 1.5 x upper limits of normal (ULN)
  • RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): AST and ALT < 2.5 x upper limits of normal (ULN)
  • RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Note: G-CSF and platelet transfusions cannot be used to increase counts to meet eligibility criteria
  • RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): =< grade 2 peripheral neuropathy
  • RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): No strong inducers of cytochrome P450 (CYP) 3A4 or CYP1A2 or strong inhibitors of CYP3A4 or CYP1A2 * Note: Ixazomib is a substrate of CYP3A4 and CYP1A2

US Trial Locations

Accepting Patients

The following is a listing of trial locations that are open and accepting patients.

SparkCures Verified Accurate, up-to-date information. Learn more


Alaska Breast Care and Surgery LLC

Anchorage, AK

Lawrence Memorial Hospital

Lawrence, KS

Lafayette Family Cancer Center

Brewer, ME

Cancer Center of Kansas (Liberal)

Liberal, KS

Cancer Center of Kansas (Chanute)

Chanute, KS

Cancer Center of Kansas (Dodge City)

Dodge City, KS

Cancer Center of Kansas (El Dorado)

El Dorado, KS

Cancer Center of Kansas (Independence)

Independence, KS

Cancer Center of Kansas (Kingman)

Kingman, KS

Cancer Center of Kansas (Newton)

Newton, KS

Saint Mary Mercy Hospital

Livonia, MI

Cancer Center of Kansas (Parsons)

Parsons, KS

Saint Luke's South Hospital

Overland Park, KS

Cancer Center of Kansas (Pratt)

Pratt, KS

Cancer Center of Kansas (Salina)

Salina, KS

Cancer Center of Kansas (Wellington)

Wellington, KS

Cancer Center of Kansas (Wichita)

Wichita, KS

Wesley Medical Center

Wichita, KS

Cancer Center of Kansas (Winfield)

Winfield, KS

Eastern Maine Medical Center

Bangor, ME

Marie Yeager Cancer Center

Saint Joseph, MI

Ingalls Memorial Hospital

Harvey, IL

Spectrum Health

Grand Rapids, MI

Saint John Macomb-Oakland Hospital

Warren, MI

St. Joseph Mercy Hospital

Ypsilanti, MI

Hickman Cancer Center

Adrian, MI

Saint Joseph Mercy (Ann Arbor)

Ann Arbor, MI

Bronson Battle Creek Cancer Care Center

Battle Creek, MI

Henry Ford Hospital

Detroit, MI

Hurley Medical Center

Flint, MI

Mercy Health Saint Mary's

Grand Rapids, MI

West Michigan Cancer Center

Kalamazoo, MI

Lakeland Hospital

Saint Joseph, MI

Sparrow Hospital

Lansing, MI

Genesys Hurley Cancer Institute

Flint, MI

Mercy Health Mercy Campus

Muskegon Heights, MI

Lakeland Community Hospital

Niles, MI

Saint Joseph Mercy (Oakland)

Pontiac, MI

Munson Medical Center

Traverse City, MI

Spectrum Health Reed City Hospital

Reed City, MI

Saint Mary's of Michigan

Saginaw, MI

Kansas City Cancer Centers (Overland Park)

Overland Park, KS

Western Illinois Cancer Treatment Center

Galesburg, IL

Alaska Women's Cancer Care

Anchorage, AK

Illinois CancerCare (Ottawa)

Ottawa, IL

Illinois CancerCare (Princeton)

Princeton, IL

Valley Radiation Oncology

Peru, IL

Cancer Care Specialists of Illinois (Swansea)

Swansea, IL

OSF Saint Francis Medical Center

Peoria, IL

Methodist Medical Center of Illinois

Peoria, IL

OSF Saint Francis Medical Center

Peoria, IL

Illinois CancerCare

Peoria, IL

Illinois CancerCare (Pekin)

Pekin, IL

Illinois CancerCare (Peru)

Peru, IL

Springfield Clinic

Springfield, IL

St. Luke's Regional Medical Center - Mountain States Tumor Institute (Boise)

Boise, ID

Saint Luke's Mountain States Tumor Institute (Fruitland)

Fruitland, ID

Saint Luke's Mountain States Tumor Institute (Meridian)

Meridian, ID

Saint Luke's Mountain States Tumor Institute (Twin Falls)

Twin Falls, ID

Saint Luke's Mountain States Tumor Institute (Nampa)

Nampa, ID

Siouxland Hematology Oncology Associates

Sioux City, IA

Providence St. Joseph's Hospital

Burbank, CA

Katmai Oncology Group

Anchorage, AK

Southern Illinois University School of Medicine

Springfield, IL

Memorial Medical Center

Springfield, IL

Illinois CancerCare (Galesburg)

Galesburg, IL

Memorial Hospital of Carbondale

Carbondale, IL

Illinois CancerCare (Eureka)

Eureka, IL

Carle Foundation Hospital (Effingham)

Effingham, IL

Crossroads Cancer Center

Effingham, IL

Decatur Memorial Hospital

Decatur, IL

Cancer Care Specialists of Central Illinois

Decatur, IL

Illinois CancerCare (Carthage)

Carthage, IL

Centralia Oncology Clinic

Centralia, IL

Illinois CancerCare (Canton)

Canton, IL

Carle Foundation Hospital (Mattoon)

Mattoon, IL

Illinois CancerCare (Bloomington)

Bloomington, IL

Rush - Copley Medical Center

Aurora, IL

Illinois CancerCare (Kewanee)

Kewanee, IL

Carle Foundation Hospital (Vermilion)

Danville, IL

Illinois CancerCare (Macomb)

Macomb, IL

Central Illinois Hematology Oncology Center

Springfield, IL

Good Samaritan Regional Health Center

Mount Vernon, IL

Rush - Copley Healthcare Center

Yorkville, IL

Carle Foundation Hospital

Urbana, IL

Hematology And Oncology Associates

Canton, OH

Alaska
Alaska Breast Care and Surgery LLC

Anchorage, AK

Alaska Women's Cancer Care

Anchorage, AK

Katmai Oncology Group

Anchorage, AK

California
Providence St. Joseph's Hospital

Burbank, CA

Idaho
St. Luke's Regional Medical Center - Mountain States Tumor Institute (Boise)

Boise, ID

Saint Luke's Mountain States Tumor Institute (Fruitland)

Fruitland, ID

Saint Luke's Mountain States Tumor Institute (Meridian)

Meridian, ID

Saint Luke's Mountain States Tumor Institute (Nampa)

Nampa, ID

Saint Luke's Mountain States Tumor Institute (Twin Falls)

Twin Falls, ID

Illinois
Rush - Copley Medical Center

Aurora, IL

Illinois CancerCare (Bloomington)

Bloomington, IL

Illinois CancerCare (Canton)

Canton, IL

Memorial Hospital of Carbondale

Carbondale, IL

Illinois CancerCare (Carthage)

Carthage, IL

Centralia Oncology Clinic

Centralia, IL

Carle Foundation Hospital (Vermilion)

Danville, IL

Cancer Care Specialists of Central Illinois

Decatur, IL

Decatur Memorial Hospital

Decatur, IL

Crossroads Cancer Center

Effingham, IL

Carle Foundation Hospital (Effingham)

Effingham, IL

Illinois CancerCare (Eureka)

Eureka, IL

Illinois CancerCare (Galesburg)

Galesburg, IL

Western Illinois Cancer Treatment Center

Galesburg, IL

Ingalls Memorial Hospital

Harvey, IL

Illinois CancerCare (Kewanee)

Kewanee, IL

Illinois CancerCare (Macomb)

Macomb, IL

Carle Foundation Hospital (Mattoon)

Mattoon, IL

Good Samaritan Regional Health Center

Mount Vernon, IL

Illinois CancerCare (Ottawa)

Ottawa, IL

Illinois CancerCare (Pekin)

Pekin, IL

Illinois CancerCare

Peoria, IL

OSF Saint Francis Medical Center

Peoria, IL

Methodist Medical Center of Illinois

Peoria, IL

OSF Saint Francis Medical Center

Peoria, IL

Illinois CancerCare (Peru)

Peru, IL

Valley Radiation Oncology

Peru, IL

Illinois CancerCare (Princeton)

Princeton, IL

Southern Illinois University School of Medicine

Springfield, IL

Springfield Clinic

Springfield, IL

Memorial Medical Center

Springfield, IL

Central Illinois Hematology Oncology Center

Springfield, IL

Cancer Care Specialists of Illinois (Swansea)

Swansea, IL

Carle Foundation Hospital

Urbana, IL

Rush - Copley Healthcare Center

Yorkville, IL

Iowa
Siouxland Hematology Oncology Associates

Sioux City, IA

Kansas
Cancer Center of Kansas (Chanute)

Chanute, KS

Cancer Center of Kansas (Dodge City)

Dodge City, KS

Cancer Center of Kansas (El Dorado)

El Dorado, KS

Cancer Center of Kansas (Independence)

Independence, KS

Cancer Center of Kansas (Kingman)

Kingman, KS

Lawrence Memorial Hospital

Lawrence, KS

Cancer Center of Kansas (Liberal)

Liberal, KS

Cancer Center of Kansas (Newton)

Newton, KS

Kansas City Cancer Centers (Overland Park)

Overland Park, KS

Saint Luke's South Hospital

Overland Park, KS

Cancer Center of Kansas (Parsons)

Parsons, KS

Cancer Center of Kansas (Pratt)

Pratt, KS

Cancer Center of Kansas (Salina)

Salina, KS

Cancer Center of Kansas (Wellington)

Wellington, KS

Cancer Center of Kansas (Wichita)

Wichita, KS

Wesley Medical Center

Wichita, KS

Cancer Center of Kansas (Winfield)

Winfield, KS

Maine
Eastern Maine Medical Center

Bangor, ME

Lafayette Family Cancer Center

Brewer, ME

Massachusetts
Michigan
Hickman Cancer Center

Adrian, MI

Saint Joseph Mercy (Ann Arbor)

Ann Arbor, MI

Bronson Battle Creek Cancer Care Center

Battle Creek, MI

Henry Ford Hospital

Detroit, MI

Genesys Hurley Cancer Institute

Flint, MI

Hurley Medical Center

Flint, MI

Mercy Health Saint Mary's

Grand Rapids, MI

Spectrum Health

Grand Rapids, MI

West Michigan Cancer Center

Kalamazoo, MI

Sparrow Hospital

Lansing, MI

Saint Mary Mercy Hospital

Livonia, MI

Mercy Health Mercy Campus

Muskegon Heights, MI

Lakeland Community Hospital

Niles, MI

Saint Joseph Mercy (Oakland)

Pontiac, MI

Spectrum Health Reed City Hospital

Reed City, MI

Saint Mary's of Michigan

Saginaw, MI

Lakeland Hospital

Saint Joseph, MI

Marie Yeager Cancer Center

Saint Joseph, MI

Munson Medical Center

Traverse City, MI

Saint John Macomb-Oakland Hospital

Warren, MI

St. Joseph Mercy Hospital

Ypsilanti, MI

North Carolina
Verified UNC Lineberger Comprehensive Cancer Center<br />University of North Carolina

SparkCures Verified Accurate, up-to-date information. Learn more

Ohio
Hematology And Oncology Associates

Canton, OH

Resources

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