Study of Oral IXAZOMIB in Combination With Melphalan and Prednisone in Patients With Newly Diagnosed Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Millennium Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01335685
First received: April 8, 2011
Last updated: May 23, 2014
Last verified: May 2014
  Purpose

This will be a phase 1/2, multicenter, 2-arm, open-label study using the oral formulation of IXAZOMIB when added to standard melphalan and prednisone (MP) treatment. Both phases of the study will include patients who have newly diagnosed multiple myeloma and are ineligible for high-dose therapy plus stem cell transplantation because of age (≥65 years of age) or coexisting conditions and for whom standard MP treatment is indicated.

Note: Phase 2 of the trial will be randomized.


Condition Intervention Phase
Multiple Myeloma
Drug: IXAZOMIB
Drug: Melphalan 9 mg/m2
Drug: Melphalan 6 mg/m2
Drug: Prednisone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Dose-Escalation, Phase 1/2 Study of the Oral Form of IXAZOMIB (MLN9708), a Next-Generation Proteasome Inhibitor, Administered in Combination With a Standard Care Regimen of Melphalan and Prednisone 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:
  • Maximum Tolerated Dose and Recommended phase 2 dose of IXAZOMIB (phase 1) [ Time Frame: Dose Limiting Toxicities determined in Cycle 1 and adverse events monitored throughout the study will inform the recommended phase 2 dose, approximately 2 years ] [ Designated as safety issue: Yes ]
    Based on toxicity and efficacy outcomes

  • Number of patients with a complete response and very good partial response (phase 2) [ Time Frame: During the induction period, approximately 1 year ] [ Designated as safety issue: No ]
    Combined response rate


Secondary Outcome Measures:
  • Maximum inhibition (Emax) and time of occurrence of Emax (TEmax) (phase 1) [ Time Frame: At multiple time points during cycles 1-3 of each phase and arm of the study, throughout approximately 84-126 days depending on the arm of the study ] [ Designated as safety issue: No ]
    Whole blood 20S proteasome inhibition parameters

  • Maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), and area under the plasma concentration-time curve (AUC) (phase 1) [ Time Frame: At multiple time points during cycles 1-3 of each phase and arm of the study, throughout approximately 84-126 days depending on the arm of the study ] [ Designated as safety issue: No ]
    Single and multiple dose plasma pharmacokinetics

  • Number of patients with response, including Complete Response, Very Good Partial Response and Partial Response (phase 1 and 2) [ Time Frame: Duration of treatment and then every 12 weeks thereafter until disease progression or initiation of subsequent antineoplastic therapy, expected duration approximately 4 years ] [ Designated as safety issue: No ]
    Overall reponse rate

  • Time to response (phase 2) [ Time Frame: From the date of enrollment to the date of the first documented response during the induction period, expected average of up to 1 year ] [ Designated as safety issue: No ]
  • Duration of response (phase 2) [ Time Frame: From the date of first response to the date of disease progression, approximately 4 years ] [ Designated as safety issue: No ]
  • Time to progression (phase 2) [ Time Frame: From date of enrollment to the date of first documented disease progression, approximately 4 years ] [ Designated as safety issue: No ]
  • Time to next therapy (phase 2) [ Time Frame: From the date of enrollment to the date of subsequent antineoplastic therapy, approximately 4 years ] [ Designated as safety issue: No ]
  • Number of patients with progression free survival (phase 2) [ Time Frame: From the date of enrollment to the date of first documented disease progression or death, approximately 4 years ] [ Designated as safety issue: No ]
  • Number of patients with overall survival (phase 2) [ Time Frame: From date of enrollment to date of death, approximately 4 years ] [ Designated as safety issue: No ]
  • Number of all adverse events (phase 2) [ Time Frame: From first dose of study drug through 30 days after last dose of study drug or until the start of subsequent antineoplastic therapy, approximately 2 years and 30 days ] [ Designated as safety issue: Yes ]
  • Assessments of Quality of Life (phase 2) [ Time Frame: At screening, Day 1 of each treatment cycle, and Days 1 and 15 of each maintenance cycle, approximately 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 164
Study Start Date: June 2011
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Twice Weekly, 6-week cycle

Phase 1 only.

Induction:

IXAZOMIB on days 1, 4, 8, 11, 22, 25, 29, 32. Melphalan 9 mg/m2 and Prednisone on days 1-4.

Repeat every 42 days for 9 cycles.

Maintenance:

IXAZOMIB only on days 1, 8, 15 in 28-day cycle.

Drug: IXAZOMIB Drug: Melphalan 9 mg/m2 Drug: Prednisone
60 mg/m2
Experimental: Once Weekly, 4-week cycle

Phases 1 and 2.

Induction:

IXAZOMIB on days 1, 8, 15. Melphalan 6 mg/m2 and Prednisone on days 1-4. Repeat every 28 days for 13 cycles.

Maintenance:

IXAZOMIB only on days 1, 8, 15 in 28-day cycle.

Drug: IXAZOMIB Drug: Melphalan 6 mg/m2 Drug: Prednisone
60 mg/m2
Experimental: Once Weekly, 6-week cycle (5weeks on/1 week off)

Phases 1 and 2

Induction:

IXAZOMIB on days 1, 8, 15, 22, 29. Melphalan 9 mg/m2 and Prednisone on days 1-4. Repeat every 42 days for 9 cycles.

Maintenance:

IXAZOMIB only on days 1, 8, 15 in 28-day cycle.

Phase 2 will include either Arm C or Arm D based on the safety, tolerability and efficacy observed in Phase 1.

Drug: IXAZOMIB Drug: Melphalan 9 mg/m2 Drug: Prednisone
60 mg/m2
Experimental: Once Weekly, 6-week cycle (2 weeks on/ 1 week off)

Phases 1 and 2

Induction:

IXAZOMIB on days 1, 8, 22, 29. Melphalan 9 mg/m2 and Prednisone on days 1-4. Repeat every 42 days for 9 cycles.

Maintenance:

IXAZOMIB only on days 1, 8, 15 in 28-day cycle.

Phase 2 will include either Arm C or Arm D based on the safety, tolerability and efficacy observed in Phase 1.

Drug: IXAZOMIB Drug: Melphalan 9 mg/m2 Drug: Prednisone
60 mg/m2

  Eligibility

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

Inclusion Criteria:

  • Male or female patient for whom standard melphalan prednisone (MP) treatment is indicated and who is not a candidate for high-dose therapy plus stem cell transplantation (HDT-SCT) for 1 of the following reasons: the patient is 65 years of age or older OR the patient is less than 65 years of age but has significant comorbid condition(s) that are likely to have a negative impact on tolerability of HDT-SCT
  • Symptomatic multiple myeloma or asymptomatic myeloma with myeloma-related organ damage diagnosed according to standard criteria
  • Measurable disease as specified in study protocol
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  • Must have adequate hematologic, liver, and renal function
  • Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to abstain from heterosexual intercourse
  • Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse
  • Voluntary written consent

Exclusion Criteria

  • Peripheral neuropathy that is greater or equal to Grade 2
  • Female patients who are lactating or pregnant
  • Major surgery or radiotherapy within 14 days before the first dose of study drug
  • Uncontrolled infection requiring systematic antibiotics
  • Diarrhea (> Grade 1)
  • Prior systemic therapy for multiple myeloma, including investigational drugs (prior treatment with corticosteroids or localized radiation therapy dose not disqualify the patient)
  • Central nervous system involvement
  • Cardiac status as described in protocol
  • Known gastrointestinal condition or procedure that could interfere with swallowing or the oral absorption of tolerance of IXAZOMIB - Diagnosis of smoldering multiple myeloma, Waldenstrom's macroglobulinemia, POEMS syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome
  • Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
  • 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 with the exception of nonmelanoma skin cancer or any completely resected carcinoma in situ
  • Serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol
  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: NCT01335685

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

  Show 32 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: NCT01335685     History of Changes
Other Study ID Numbers: C16006, 2010-023772-71
Study First Received: April 8, 2011
Last Updated: May 23, 2014
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency

Additional relevant MeSH terms:
Prednisone
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Melphalan
Alkylating Agents
Anti-Inflammatory Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014