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Phase II Study of IRD (Ixazomib, Lenalidomide, Dexamethasone) Post Autologous Stem Cell Transplantation Followed by Maintenance Ixazomib or Lenalidomide for Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT02253316
Recruitment Status : Recruiting
First Posted : October 1, 2014
Last Update Posted : August 31, 2018
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:
The purpose of this research study is to evaluate a treatment regimen called IRD which will be given to participants after their stem cell transplant in an effort to help prolong the amount of time the participants are disease-free after transplant. IRD is a three-drug regimen consisting of ixazomib, lenalidomide (also called Revlimid), and dexamethasone. After 4 cycles of IRD, the participants will be randomized to receive maintenance therapy either with ixazomib or lenalidomide.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Biological: Ixazomib Drug: Lenalidomide Drug: Dexamethasone Phase 2

Detailed Description:

Based on the further need to improve progression-free survival and overall survival post-autologous stem cell transplantation (ASCT) for multiple myeloma and the benefits seen of consolidation/maintenance treatment with immunomodulatory drugs thalidomide and lenalidomide and the proteasome inhibitor bortezomib, the natural next step is to evaluate combination regimens of immunomodulatory drugs and proteasome inhibitors as consolidation/maintenance post-ASCT. The regimen consisting of ixazomib, lenalidomide, and dexamethasone (IRD) has been shown to have low toxicity, and the availability of an oral formulation of ixazomib allows for easier administration when compared to bortezomib.

In this study, following consolidation with IRD, patients will be randomized to maintenance therapy with lenalidomide or ixazomib in order to collect pilot data comparing the toxicity and efficacy of maintenance therapy with immunomodulatory drugs and proteasome inhibitors.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of IRD (Ixazomib, Lenalidomide, & Dexamethasone) for Consolidation Therapy Post Autologous Stem Cell Transplantation Followed by Maintenance Ixazomib or Lenalidomide for Multiple Myeloma
Actual Study Start Date : January 20, 2015
Estimated Primary Completion Date : January 31, 2019
Estimated Study Completion Date : January 31, 2023


Arm Intervention/treatment
Experimental: Consolidation: Ixazomib, Lenalidomide, & Dexamethasone
Consolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, & dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 55 mg of lenalidomide will be administered on daily on Days 1-21.
Biological: Ixazomib
Other Names:
  • [14C]-ixazomib
  • [14C]-MLN9708

Drug: Lenalidomide
Other Name: Revlimid

Drug: Dexamethasone
Other Names:
  • Aeroseb-Dex
  • Alba-Dex
  • Decaderm
  • Decadrol
  • Decadron
  • Decasone R.p.
  • Decaspray
  • Deenar
  • Deronil
  • Dex-4
  • Dexace
  • Dexameth
  • Dezone
  • Gammacorten
  • Hexadrol
  • Maxidex
  • Sk-Dexamethasone

Experimental: Maintenance Arm 1: Ixazomib
Ixazomib will be administered on Days 1, 8, and 15 of a 28-day cycle at a starting dose of 4 mg until patient progresses or experiences an unacceptable toxcity.
Biological: Ixazomib
Other Names:
  • [14C]-ixazomib
  • [14C]-MLN9708

Experimental: Maintenance Arm 2: Lenalidomide
Lenalidomide will be administered daily continuously for a 28-day cycle at a starting dose of 10 mg. If lenalidomide is tolerated well (i.e. no dose modification required) during the first three cycles, lenalidomide dose will be increased to 15 mg daily and will continue until patient progresses or experiences an unacceptable toxicity.
Drug: Lenalidomide
Other Name: Revlimid




Primary Outcome Measures :
  1. Improvement in minimal residual disease (MRD) [ Time Frame: After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment) ]
    For the purposes of this study, a patient will be considered as having minimal residual diseases if a positive result is obtained using the Adaptive Clonoseq MRD testing. In the event that Adaptive Clonoseq cannot be performed, a patient will be considered as having minimal residual diseases if a positive result is obtained using the Mayo MFC MRD Panel.


Secondary Outcome Measures :
  1. MRD-negative rate after ASCT [ Time Frame: Prior to beginning consolidation treatment (Day -28 to Day 0) ]
  2. Toxicity of IRD consolidation [ Time Frame: Up to 30 days following completion of IRD consolidation treatment (approximately Day 142 of consolidation treatment) ]
    The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.

  3. Response rate of IRD consolidation [ Time Frame: After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment) ]
    Response will be determined by the International Myeloma Working Group (IMWG) Uniform Response Criteria.

  4. Progression-free survival of IRD consolidation [ Time Frame: After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment) ]
    Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.

  5. Overall survival of IRD consolidation [ Time Frame: After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment) ]
    Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.

  6. Compare toxicity between the two maintenance arms [ Time Frame: 30 days after the completion of maintenance treatment (Approximately Day 1125 of maintenance treatment) ]
    The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.

  7. Compare response rate between the two maintenance arms [ Time Frame: Completion of maintenance treatment (Approximately Day 1095 of maintenance treatment) ]
    Response will be determined by the International Myeloma Working Group (IMWG) Uniform Response Criteria.

  8. Compare progression-free survival between the two maintenance arms [ Time Frame: 18 months after completion of maintenance therapy (Up to 5 years after starting the study) ]
    Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.

  9. Compare overall survival between the two maintenance arms [ Time Frame: 18 months after completion of maintenance therapy (Up to 5 years after starting the study) ]
    Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.

  10. Rate of MRD-positive to MRD-negative conversion between the two maintenance arms [ Time Frame: Cycle 13 Day 1 of maintenance treatment (Approximately Day 364 of maintenance treatment) ]
  11. Association of progression-free survival with MRD-negativity [ Time Frame: After 4 cycles of IRD consolidation treatment (Approximately Day 112 of consolidation treatment) ]
    Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.

  12. Association of progression-free survival with MRD-positivity [ Time Frame: After 4 cycles of IRD consolidation treatment (Approximately Day 112 of consolidation treatment) ]
    Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.

  13. Association of overall survival with MRD-negativity [ Time Frame: After 4 cycles of IRD consolidation treatment (Approximately Day 112 of consolidation treatment) ]
    Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.

  14. Association of overall survival with MRD-positivity [ Time Frame: After 4 cycles of IRD consolidation treatment (Approximately Day 112 of consolidation treatment) ]
    Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.



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.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Each patient must meet all of the following inclusion criteria to begin IRD Consolidation:

  • Between the ages of 18 and 70 years of age (inclusive) at time of enrollment
  • 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 patient at any time without prejudice to future medical care
  • Histologically confirmed diagnosis of symptomatic multiple myeloma. (Patients with multiple myeloma with secondary amyloidosis are eligible.)
  • Received at least two cycles of any regimen as initial systemic therapy for multiple myeloma and are within 2-16 months of the first dose of initial therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2
  • Adequate organ function as defined below:

Absolute neutrophil count (ANC) >= 1,000 mm^3 Platelet count >= 75,000/mm^3; platelet transfusions to help patient meet eligibility criteria are not allowed within 7 days before study enrollment Total bilirubin <= 1.5 x upper limit of normal range (ULN) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=3 x ULN Calculated creatinine clearance >= 30 mL/min

  • Women of childbearing potential must follow pregnancy testing requirements as outlined in the Revlimid REMS program material. This is defined as either committing to continued abstinence from heterosexual intercourse or beginning TWO acceptable methods of contraception (one highly effective method and one additional effective method AT THE SAME TIME) at least 28 days prior to the start of lenalidomide, for the duration of study participation, and for 28 days following the last dose of lenalidomide. Women of childbearing potential must also agree to ongoing pregnancy testing.
  • Men must agree to use a latex condom during sexual contact with a woman of childbearing potential even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • All study participants must be registered into the mandatory Revlimind REMS program and be willing to comply with its requirements. Per standard Revlimid REMS program requirements, all physicians who prescribe lenalidomide for research subjects enrolled into this trial, must be registered in, and must comply with, all requirements of the Revlimid REMS program.

Exclusion Criteria

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

  • Female patients who are lactating or have a positive serum pregnancy test during the screening period
  • Evidence of MM disease progression any time prior to enrollment. Progression from smoldering/asymptomatic MM to symptomatic MM is not exclusionary.
  • Tandem autologous transplantation
  • History of plasma cell leukemia or MM CNS involvement
  • Administration or planned administration of any other concomitant chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy which would be considered a treatment of multiple myeloma until Day +28 post-transplant through discontinuation from study. Patients may be on corticosteroids if they are being given for disorders other than multiple myeloma (e.g., adrenal insufficiency, rheumatoid arthritis, etc.)
  • Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
  • Prior organ transplant requiring immunosuppressive therapy
  • Active hepatitis A, B or C virus infection, or known human immunodeficiency virus (HIV) positive
  • Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
  • Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib
  • Concurrent hematologic or non-hematologic malignancy requiring treatment (other than multiple myeloma and secondary amyloidosis)
  • Cardiac syncope, uncompensated NYHA Class 3 or 4 congestive heart failure, myocardial infarction within the previous six months, unstable angina pectoris, clinically significant repetitive ventricular arrhythmias despite antiarrhythmic treatment, severe orthostatic hypotension, or clinically important autonomic disease
  • Grade >= 3 peripheral neuropathy, or Grade 2 with pain on clinical examination during the screening period
  • Major surgery within 14 days prior to start of study treatment
  • Infection requiring systemic antibiotic therapy or other serious infection within 14 days prior to start of study treatment
  • Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days prior to start of study treatment and throughout the duration of this trial

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): NCT02253316


Contacts
Contact: Ravi Vij, M.D. 314-454-8323 rvij@wustl.edu

Locations
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Nitya Nathwani, MD    626-256-4673 ext 65295    nnathwani@coh.org   
Principal Investigator: Nitya Nathwani, MD         
Sub-Investigator: Ahmed Aribi, MD         
Sub-Investigator: Ibrahim Aldoss, MD         
Sub-Investigator: Monzr Al-Malki, MD         
Sub-Investigator: Elizabeth Budde, MD         
Sub-Investigator: Ji-Lian Cai, MD         
Sub-Investigator: Thai Cao, MD         
Sub-Investigator: Robert Chen, MD         
Sub-Investigator: Leonardo Farol, MD         
Sub-Investigator: Stephen Forman, MD         
Sub-Investigator: Alex Herrera, MD         
Sub-Investigator: Myo Htut, MD         
Sub-Investigator: Chatchada Karanes, MD         
Sub-Investigator: Khaled Samer, MD         
Sub-Investigator: Amrita Krishnan, MD         
Sub-Investigator: Matthew Mei, MD         
Sub-Investigator: Auayporn Nademanee, MD         
Sub-Investigator: Ryotaro Nakamura, MD         
Sub-Investigator: Margaret O'Donnell, MD         
Sub-Investigator: Pablo Parker, MD         
Sub-Investigator: Leslie Popplewell, MD         
Sub-Investigator: Michael Rosenzweig, MD         
Sub-Investigator: Firoozeh Sahebi, MD         
Sub-Investigator: Amandeep Salhotra, MD         
Sub-Investigator: Tanya Siddiqi, MD         
Sub-Investigator: David Snyeder, MD         
Sub-Investigator: George Somlo, MD         
Sub-Investigator: Ricardo Spielberger, MD         
Sub-Investigator: Anthony Stein, MD         
Sub-Investigator: Jasmine Zain, MD         
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Thomas G. Martin, MD    415-353-2051    tom.martin@ucsf.edu   
Principal Investigator: Thomas G. Martin, MD         
United States, Colorado
Colorado Blood Cancer Institute Recruiting
Denver, Colorado, United States, 80218
Contact: Tara K Gregory, M.D.    720-754-4800    Tara.Gregory@HealthONECares.com   
Principal Investigator: Tara K Gregory, M.D.         
Sub-Investigator: Alireza B Maris, M.D.         
Sub-Investigator: Jeffrey V Matous, M.D.         
Sub-Investigator: Peter A McSweeney, M.D.         
Sub-Investigator: Richard Nash, M.D.         
Sub-Investigator: Marcello Rotta, M.D.         
Sub-Investigator: Michael T Tees, M.D.         
United States, Georgia
Emory University - Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Jonathan L Kaufman, MD    404-778-1900    jlkaufm@emory.edu   
United States, Michigan
Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Jeffrey A Zonder, MD    313-576-8732    zonderj@karmanos.org   
Principal Investigator: Jeffrey A. Zonder, M.D.         
Sub-Investigator: Abhinav Deol, MD         
Sub-Investigator: Radhakrishnan Ramchandren, MD         
Sub-Investigator: Melissa Runge-Morris, MD         
Sub-Investigator: Charles Schiffer, MD         
Sub-Investigator: Jay Yang, MD         
Sub-Investigator: Steven Burt, MD         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Francis K Buadi, M.D.    (507) 538-3270    Buadi.Francis@mayo.edu   
Principal Investigator: Francis K Buadi, M.D.         
Sub-Investigator: Angela Dispenzieri, M.D.         
Sub-Investigator: Matthew T Drake, M.D., Ph.D.         
Sub-Investigator: Amie L Fonder, PA-C         
Sub-Investigator: Morie Gertz, M.D.         
Sub-Investigator: Ronald S Go, M.D.         
Sub-Investigator: Wilson I Gonsalves, M.D.         
Sub-Investigator: Suzanne R Hayman, M.D.         
Sub-Investigator: Miriam A Hobbs, APRN, CNP, DNP         
Sub-Investigator: Yi (Lisa) L Hwa, APRN, CNP, DNP         
Sub-Investigator: Prashant Kapoor, M.D.         
Sub-Investigator: Taxiarchis Kourelis, M.D.         
Sub-Investigator: Shaji K Kumar, M.D.         
Sub-Investigator: Nelson Leung, M.D.         
Sub-Investigator: Yi Lin, M.D., Ph.D.         
Sub-Investigator: John A Lust, M.D., Ph.D.         
Sub-Investigator: S. Vincent Rajkumar, M.D.         
Sub-Investigator: Stephen J Russell, M.D., Ph.D.         
Sub-Investigator: Thomas E Witzig, M.D.         
Sub-Investigator: Steven R Zeldenrust, M.D, Ph.D.         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 62864
Contact: Ravi Vij, M.D.    314-454-8323    rvij@wustl.edu   
Principal Investigator: Ravi Vij, M.D.         
Sub-Investigator: Camille Abboud, M.D.         
Sub-Investigator: John DiPersio, M.D., Ph.D.         
Sub-Investigator: Todd Fehniger, M.D., Ph.D.         
Sub-Investigator: Armin Ghobadi, M.D.         
Sub-Investigator: Megan Jacoby, M.D., Ph.D.         
Sub-Investigator: Jesse Keller, M.D.         
Sub-Investigator: Iskra Pusic, M.D.         
Sub-Investigator: Rizwan Romee, M.D.         
Sub-Investigator: Mark Schreoder, M.D.         
Sub-Investigator: Keith Stockerl-Goldstein, M.D.         
Sub-Investigator: Michael Tomasson, M.D.         
Sub-Investigator: Geoffrey Uy, M.D.         
Sub-Investigator: Matthew Walter, M.D.         
Sub-Investigator: Lukas Wartman, M.D.         
Sub-Investigator: John Welch, M.D., Ph.D.         
Sub-Investigator: Peter Westervelt, M.D., Ph.D.         
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Ajai Chari, M.D.    212-241-7873    ajai.chari@mountsinai.org   
Principal Investigator: Ajai Chari, M.D.         
Sub-Investigator: Sundar Jagannath, M.D.         
Sub-Investigator: Hearn Cho, M.D.         
Sub-Investigator: Samir Parekh, M.D.         
Sub-Investigator: Deepu Madduri, M.D.         
United States, Ohio
Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Ashley Rosko, M.D.    614-293-7807    Ashley.Rosko@osumc.edu   
Principal Investigator: Ashley Rosko, M.D.         
Sub-Investigator: Don Benson, Jr., M.D., Ph.D.         
Sub-Investigator: Jonathan Brammer, M.D.         
United States, Tennessee
Tennessee Oncology, PLLC Recruiting
Nashville, Tennessee, United States, 37203
Contact: Jesus Berdeja, M.D.    615-329-7274    jberdeja@tnonc.com   
Principal Investigator: Jesus Berdeja, M.D.         
Sponsors and Collaborators
Washington University School of Medicine
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Ravi Vij, M.D. Washington University School of Medicine

Additional Information:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02253316     History of Changes
Other Study ID Numbers: 201411060
First Posted: October 1, 2014    Key Record Dates
Last Update Posted: August 31, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Washington University School of Medicine:
Multiple Myeloma
Autologous Stem Cell Transplantation
Ixazomib
Lenalidomide
Dexamethasone

Additional relevant MeSH terms:
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
Dexamethasone acetate
Dexamethasone
Lenalidomide
Ixazomib
Thalidomide
BB 1101
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