Trial record 1 of 1 for:    NCT02046070
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Phase 2 Study to Evaluate the Oral Combination of IXAZOMIB With Cyclophosphamide and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma (NDMM)

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:
NCT02046070
First received: December 12, 2013
Last updated: June 12, 2014
Last verified: June 2014
  Purpose

This is a phase 2, multicenter, open-label study in patients with NDMM who have not received prior systemic treatment for multiple myeloma (MM) and who are ineligible for high-dose therapy (HDT)-SCT due to age (ie, ≥ 65 years) or comorbid disease(s).


Condition Intervention Phase
Multiple Myeloma
Drug: Cyclophosphamide (300mg/m^2)
Drug: Cyclophosphamide (400mg/m^2)
Drug: IXAZOMIB
Drug: Dexamethasone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Phase 2 Study to Evaluate the Oral Combination of IXAZOMIB (MLN9708) With Cyclophosphamide and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Requiring Systemic Treatment

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Combined response rate of CR (including sCR) + VGPR in patients treated with IXAZOMIB when added to a standard care regimen of Cyclophosphamide and Dexamethasone (Cd) during the induction phase [ Time Frame: 28-day cycles of treatment of IXAZOMIB + Cyclophosphamide on days 1, 8, 15 and Dexamethasone on days 1, 8, 15, 22 for approximately 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • All AEs, Grade 3 or higher AEs, AEs resulting in discontinuation, AEs resulting in dose reduction, serious adverse events (SAEs), and assessments of clinical laboratory values [ Time Frame: Recorded from the first dose of drug in the study drug regimen through 30 days after last dose of drug in the study drug regimen ] [ Designated as safety issue: Yes ]
  • PK parameters [ Time Frame: Days 1-3, 5, 8, 15-17, 19 and 22 during cycle 1 and day 1 of cycle 2 (safety lead-in patients) or days 1, 8, 15, and 22 during cycles 1-3 (excluding safety lead-in) ] [ Designated as safety issue: No ]
    Includes single-dose maximum (peak) concentration (Cmax), single-dose first time of occurrence of maximum (peak) concentration (Tmax), and area under the plasma concentration versus time curve (AUC)

  • ORR (Overall response rate, CR + VGPR + PR), CR, VGPR, and PR during the induction phase and throughout the entire study [ Time Frame: Time from the start of treatment to the occurrence of disease progression, unacceptable toxicities, discontinuation of study due to any other reasons, or end of study (EOS) up to 60 months ] [ Designated as safety issue: No ]
  • Time to Response (TTR) [ Time Frame: Time from the date of enrollment to the date of first documented response during induction phase up to 36 months ] [ Designated as safety issue: No ]
  • Duration of Response (DOR) [ Time Frame: Time interval from the date of first response to the date of disease progression up to 60 months ] [ Designated as safety issue: No ]
  • Time to Progression (TTP) [ Time Frame: Time interval from the date of enrollment to the date of first documented disease progression up to 60 months ] [ Designated as safety issue: No ]
  • Progression Free Survival (PFS) [ Time Frame: Time interval from the date of enrollment to the date of first documented disease progression or death up to 60 months ] [ Designated as safety issue: No ]
  • AEs, SAEs, AEs resulting in discontinuation, AEs resulting in dose reduction in patients remaining on treatment after 13 cycles. [ Time Frame: From signing of the informed consent form through 30 days after the last dose of drug in the study drug regimen ] [ Designated as safety issue: Yes ]
  • Comparison of change in global health status between baseline and each post-baseline assessment, as measured by the global health scale, functioning, and symptoms of the EORTC QLQ-C30 and MY-20 [ Time Frame: Day 1 of each 28-day cycle ] [ Designated as safety issue: No ]
  • ORR, CR, VGPR, and PR of single agent IXAZOMIB as maintenance therapy in patients remaining on treatment after 13 cycles [ Time Frame: From signing of the informed consent form through 30 days after the last dose of drug in the study drug regimen ] [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: March 2014
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IXAZOMIB + 300mg/m^2 Cyclophosphamide
Induction: IXAZOMIB + Cyclophosphamide (300mg/m^2) + Dexamethasone. Maintenance: IXAZOMIB.
Drug: Cyclophosphamide (300mg/m^2)
Induction. Days 1, 8, 15 and dexamethasone on days 1, 8, 15, 22. Repeat every 28 days for 13 cycles in the absence of progressive disease (PD)/death or unacceptable toxicity.
Drug: IXAZOMIB
Days 1, 8, 15 during 28-day cycles until PD/death or unacceptable toxicity
Drug: Dexamethasone
Days 1, 8, 15, 22. Repeat every 28 days for 13 cycles in the absence of progressive disease (PD)/death or unacceptable toxicity.
Experimental: IXAZOMIB + 400mg/m^2 Cyclophosphamide
Induction: IXAZOMIB + Cyclophosphamide (400mg/m^2) + Dexamethasone. Maintenance: IXAZOMIB.
Drug: Cyclophosphamide (400mg/m^2)
Induction. Days 1, 8, 15 and dexamethasone on days 1, 8, 15, 22. Repeat every 28 days for 13 cycles in the absence of progressive disease (PD)/death or unacceptable toxicity.
Drug: IXAZOMIB
Days 1, 8, 15 during 28-day cycles until PD/death or unacceptable toxicity
Drug: Dexamethasone
Days 1, 8, 15, 22. Repeat every 28 days for 13 cycles in the absence of progressive disease (PD)/death or unacceptable toxicity.

  Eligibility

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

Inclusion Criteria:

  1. Adult male or female patients 18 years of age or older with a confirmed diagnosis of symptomatic multiple myeloma (MM) according to standard criteria who have not received prior treatment for MM.
  2. Patients for whom cyclophosphamide and dexamethasone treatment is appropriate and who are considered not eligible for HDT-SCT for 1 or more of the following reasons:

    • Patient is ≥ 65 years of age.
    • Patient is ≤ 65 years of age but has significant comorbid condition(s) that are, in the opinion of the investigator, likely to have a negative impact on tolerability of HDT-SCT.
  3. Measurable disease as defined in the protocol.
  4. Meets clinical laboratory values as defined in the protocol.
  5. Eastern Cooperative Oncology Group performance status of 0, 1, or 2.
  6. Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to practice true abstinence.

    Male patients who agree to practice effective barrier contraception or agree to practice true abstinence.

  7. Voluntary written consent.
  8. Suitable venous access for the study-required blood sampling.
  9. Patient is willing and able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

Patients meeting any of the following exclusion criteria are not to be randomized to treatment:

  1. Prior treatment for multiple myeloma with either standard of care treatment or investigational regimen.
  2. Diagnosis of smoldering MM, Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
  3. Central nervous system involvement.
  4. Diagnosed or treated for another malignancy within 2 years before the first dose or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
  5. Peripheral neuropathy Grade 1 with pain or ≥ Grade 2 of any cause.
  6. Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of study drug, including difficulty swallowing.
  7. Infection requiring IV antibiotic therapy or other serious infection within 14 days before the first dose of study drug.
  8. Ongoing or active infection, known HIV positive, active hepatitis B or C infection
  9. Systemic treatment with strong inhibitors of CYP1A2 or CYP3A, or strong CYP3A inducers, or use of Ginkgo biloba or St. John's wort within 14 days before the first dose of study treatment.
  10. Known allergy to any of the study medications, their analogues, or excipients in the various formulations.
  11. Major surgery within 14 days before the first dose of study drug.
  12. Female patients who are lactating and breastfeeding or pregnant.
  13. Serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol.
  14. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
  15. Treatment with any investigational products for reasons other than MM within 30 days before the first dose of study drug.
  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: NCT02046070

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

Locations
Greece
Recruiting
Athens, Attiki, Greece
Sweden
Recruiting
Stockholm, Sodermanlands lan, Sweden
Recruiting
Lund, Sweden
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: NCT02046070     History of Changes
Other Study ID Numbers: C16020, 2013-003113-17
Study First Received: December 12, 2013
Last Updated: June 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Millennium Pharmaceuticals, Inc.:
MLN9708
Newly diagnosed
NDMM
IXAZOMIB

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
Cyclophosphamide
Dexamethasone
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on September 15, 2014