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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Millennium Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01564537
First received: March 22, 2012
Last updated: June 6, 2014
Last verified: June 2014
  Purpose

The purpose of this phase 3, randomized, double-blind, multicenter study is to compare Oral IXAZOMIB plus Lenalidomide and Dexamethasone versus Placebo plus Lenalidomide and Dexamethasone in adult patients with relapsed and/or refractory multiple myeloma.


Condition Intervention Phase
Relapsed Multiple Myeloma
Refractory Multiple Myeloma
Drug: IXAZOMIB + Lenalidomide + Dexamethasone
Drug: Placebo + Lenalidomide + Dexamethasone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind, Multicenter Study Comparing Oral IXAZOMIB (MLN9708) Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Relapsed and/or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Millennium Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Progression free survival (PFS) [ Time Frame: Change from the time of screening; Day 1 of each cycle; at EOT and thereafter every 4 weeks until disease progression ] [ Designated as safety issue: No ]
    To determine whether the addition of oral IXAZOMIB to the background therapy of lenalidomide and dexamethasone improves PFS in patients with relapsed and/or refractory multiple myeloma


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: At the time of screening; Day 1 of each cycle; at EOT; every 4 weeks until disease progression and thereafter every 12 weeks until death or study termination ] [ Designated as safety issue: No ]
    To determine whether the addition of oral IXAZOMIB to lenalidomide and dexamethasone improves OS

  • Overall Response Rate (ORR), including Partial Response (PR), Very Good Partial Response (VGPR), and Complete Response (CR) [ Time Frame: At the time of screening; Day 1 of each cycle; at EOT and thereafter every 4 weeks until disease progression ] [ Designated as safety issue: No ]
    Standard multiple myeloma disease assessments

  • CR + VGPR [ Time Frame: At the time of screening; Day 1 of each cycle; at EOT and thereafter every 4 weeks until disease progression ] [ Designated as safety issue: No ]
    Standard multiple myeloma disease assessments

  • Duration of Response (DOR) [ Time Frame: At the time of screening; Day 1 of each cycle; at EOT and thereafter every 4 weeks until disease progression ] [ Designated as safety issue: No ]
  • Time to Progression (TTP) [ Time Frame: At the time of screening; Day 1 of each cycle; at EOT and thereafter every 4 weeks until disease progression ] [ Designated as safety issue: No ]
  • Number of AEs, SAEs, assessment of clinical laboratory values and evaluate Eastern Cooperative Group (ECOG) performance scores [ Time Frame: From the date of signing of the informed consent form through 30 days after the last dose of study drug ] [ Designated as safety issue: Yes ]
    To determine the safety of addition of IXAZOMIB to lenalidomide and dexamethasone

  • Pain response rate as assessed by the BFI-SF and analgesic use [ Time Frame: BPI-SF will be assessed at screening; Day 1 of each cycle; at EOT and thereafter every 4 weeks until disease progression ] [ Designated as safety issue: No ]
  • Change in global health status, as measured by the patient reported outcome questionnaires, EORTC QLQ-C30 and MY-20 [ Time Frame: At the time of screening, Day 1 of Cycle 1 and Cycle 2; every other cycle until EOT; every 4 weeks after EOT until disease progression and thereafter every 12 weeks until OS ] [ Designated as safety issue: No ]
  • OS and PFS in high-risk population such as those carrying del(13), del(17), +1q21, t(4;14), or t(14;16) [ Time Frame: At the time of screening; Day 1 of each cycle; at EOT; every 4 weeks until disease progression and thereafter every 12 weeks until death or study termination ] [ Designated as safety issue: Yes ]
  • To collect PK data including Cmax, AUC and Tmax to contribute to population PK analyses [ Time Frame: Days 1 & 14 of cycles 1&2. Day 1 of cycles 3-10 ] [ Designated as safety issue: No ]

Estimated Enrollment: 703
Study Start Date: August 2012
Estimated Study Completion Date: May 2019
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: IXAZOMIB
IXAZOMIB + Lenalidomide + Dexamethasone
Drug: IXAZOMIB + Lenalidomide + Dexamethasone
Patients will receive single oral dose of IXAZOMIB (4.0mg) on days 1,8,15 and single oral dose of Lenalidomide (25mg) on days 1-21 and single oral dose of Dexamethasone (40mg) on days 1,8, 15 and 22 every 28 days until disease progression
Placebo Comparator: Placebo
Placebo + Lenalidomide + Dexamethasone
Drug: Placebo + Lenalidomide + Dexamethasone
Patients will receive single oral dose of Placebo on days 1,8,15 and single oral dose of Lenalidomide (25mg) on days 1-21 and single oral dose of Dexamethasone (40mg) on days 1,8, 15 and 22 every 28 days until disease progression

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients 18 years or older
  • Diagnosed Multiple Myeloma according to standard criteria
  • Measurable disease as specified in study protocol
  • Eastern Cooperative Oncology Group (ECOG)performance status of 0 to 2
  • Patients with relapsed and/or refractory Multiple Myeloma who have received 1 to 3 prior therapies
  • Meet the clinical laboratories criteria as specified in the protocol
  • Patients who received prior allogenic transplant must have no active graft-versus-host disease (GVHD)
  • Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to abstain from heterosexual intercourse; must also adhere to the guidelines of the lenalidomide pregnancy prevention program
  • Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse AND must adhere to the guidelines of the lenalidomide pregnancy prevention program
  • Must be able to take concurrent aspirin 325 mg daily
  • Voluntary written consent

Exclusion Criteria:

  • Patient who were refractory to lenalidomide or proteasome inhibitor-based therapy
  • Female patients who are lactating or pregnant
  • Major surgery or radiotherapy within 14 days before randomization
  • Infection requiring systematic antibiotics within 14 days before the first dose of study drug
  • Central nervous system involvement
  • Failure to have fully recovered from the effects of prior chemotherapy regardless of the interval since last treatment
  • Systemic treatment with strong inhibitors of CYP1A2, strong inhibitors of CYP3A, or strong CYP3A inducers, or use of Ginko biloba or St. John's wort within 14 days before the first dose of study treatment
  • Diagnosis of Waldenstrom's macroglobulinemia, POEMS syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome
  • Evidence of current uncontrolled cardiovascular conditions
  • Serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol
  • Known allergy to any of the study medications
  • Known gastrointestinal condition or procedure that could interfere with swallowing or the oral absorption of tolerance of IXAZOMIB - Diagnosed or treated for another malignancy within 2 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease with the exception of nonmelanoma skin cancer or any completely resected carcinoma in situ
  • Ongoing or active systemic infection, active hepatitis B virus infect, active hepatitis C infection, or known human immunodeficiency virus (HIV) positive
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01564537

Contacts
Contact: For an updated listing of recruitment sites contact: Millennium Medical and Drug Information Center 1-877-674-3784 medical@mlnm.com

  Show 149 Study Locations
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01564537     History of Changes
Other Study ID Numbers: C16010, 2011-005496-17, CTR20130908
Study First Received: March 22, 2012
Last Updated: June 6, 2014
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency

Keywords provided by Millennium Pharmaceuticals, Inc.:
Relapsed multiple myeloma
Refractory multiple myeloma
IXAZOMIB
MLN9708
Proteasome inhibitor
Tourmaline-MM1

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
Dexamethasone 21-phosphate
Lenalidomide
Thalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids

ClinicalTrials.gov processed this record on September 16, 2014