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BrUOG 299 :Ixazomib, Oral Metronomic Cyclophosphamide and Dexamethasone for First-Line Treatment of Multiple Myeloma: A Phase II Brown University Oncology Group Study.

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ClinicalTrials.gov Identifier: NCT02412228
Recruitment Status : Recruiting
First Posted : April 9, 2015
Last Update Posted : November 30, 2018
Sponsor:
Collaborators:
Rhode Island Hospital
The Miriam Hospital
Memorial Hospital of Rhode Island
Information provided by (Responsible Party):
John Reagan, Brown University

Brief Summary:
The goal of this proposal is to develop a more effective and better tolerated regimen. Ixazomib appears to have greater activity than bortezomib with less peripheral neuropathy.

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: BrUOG 299: Ixazomib, Oral Metronomic Cyclophosphamide and Dexamethasone for First-Line Treatment of Multiple Myeloma: A Phase II Brown University Oncology Group Study.
Study Start Date : August 2015
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : September 2019


Arm Intervention/treatment
Experimental: Ixazomib Regimen

Cycle 1: Ixazomib: 4mg/day 1, 8, 15, Cyclophosphamide: 50 mg/day continuous daily, Dexamethasone: 20 mg/day 1, 8, 15 Cycles 2-6: Ixazomib: 4mg/day 1, 4, 8, 11, 15, 18, Cyclophosphamide: 50 mg/day continuous, daily, Dexamethasone: 20 mg/day 1, 4, 8, 11, 15, 18

Maintenance:

Ixazomib at 4 mg days 1, 8 and 15 of a 28 day cycle for 1 ½ years

Drug: Ixazomib

Cycle 1:

Ixazomib: 4mg/day 1, 8, 15

Cycles 2-6:

Ixazomib: 4mg/day 1, 4, 8, 11, 15, 18,

Maintenance:

Ixazomib at 4 mg days 1, 8 and 15 of a 28 day cycle for 1 ½ years

Other Name: MLN978

Drug: Cyclophosphamide

Cycle 1:

Cyclophosphamide: 50 mg/day continuous daily

Cycles 2-6:

Cyclophosphamide: 50 mg/day continuous daily


Drug: Dexamethasone

Cycle 1:

Dexamethasone: 20 mg/day 1, 8, 15

Cycles 2-6:

Dexamethasone: 20 mg/day 1, 4, 8, 11, 15, 18





Primary Outcome Measures :
  1. Response rate of Ixazomib with metronomic cyclophosphamide and dexamethasone for first-line treatment of multiple myeloma [ Time Frame: Monthly for 6 months then every 2 months until progression, approximately 2 years. ]


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

Inclusion Criteria:

  • Age ≥ 18 years of age
  • Histologically confirmed multiple myeloma according to WHO classification. Pathology report to be sent to BrUOG for confirmation
  • Diagnosis of Multiple Myeloma that has not been previously treated (although patients that received emergent steroid and/or local radiation therapy will be permitted to enter the study). , Details need to be submitted to BrUOG with dates and doses.
  • Measureable disease defined as either an elevated serum M-protein, urine M-protein, bone marrow involvement >30% or serum free light chains per the IMWG criteria. Confirmation to be sent to BrUOG, see section 7 for criteria
  • Life expectancy of ≥ 6 months, confirmation per treating investigator required
  • Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet count ≥ 75,000/mm3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment. If transfusional support provided, please document for submission to BrUOG
  • Calculated creatinine clearance ≥30 mL/min (based on the Cockcroft-Gault Equation below)

For males:

Creatinine Clearance = (140-age[years] x weight [kg]) 72 x (serum creatinine[mg/dL])

For females:

Creatinine Clearance = 0.85 (140-age[years] x weight [kg]) 72 x (serum creatinine[mg/dL])

  • ECOG performance status of 0-1.
  • Adequate Liver function; AST or ALT < 3.0 x upper limit of normal (ULN); Total bilirubin <1.5x ULN
  • 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.
  • Female patients who:

    • Are postmenopausal for at least 1 year before the screening visit, OR
    • Are surgically sterile, OR
    • If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug and obtain a pregnancy test, which must come back negative prior to drug, OR
    • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject and obtain a serum pregnancy test, which must come back negative prior to drug. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.) Documentation and confirmation of conversations and patient commitment to contraception is required to be noted and sent to BrUOG. Female's menopausal status to be documented and submitted to BrUOG if applicable. Pregnancy test, if applicable, required to be sent to BrUOG.
  • Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following:

    • Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
    • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.) Documentation and confirmation of conversations and patient commitment to contraception is required to be noted and sent to BrUOG.

Exclusion Criteria:

  • Female patients who are lactating or have a positive serum pregnancy test during the screening period.
  • Any surgery within 14 days before enrollment.
  • Radiotherapy within 14 days before enrollment.
  • Central nervous system involvement (myeloma-related).
  • Active infection requiring systemic antibiotic therapy or other serious active infection within 7 days before study enrollment.
  • Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
  • Systemic treatment, within 14 days before the first dose of ixazomib, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort.
  • Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive.
  • Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol. If not applicable, then investigator to document not applicable
  • Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent. If not applicable, then investigator to document not applicable
  • Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing. If not applicable, then investigator to document not applicable
  • Diagnosed or treated for another malignancy within 2 years before study enrollment 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.
  • Patient has ≥ Grade 2 peripheral neuropathy or Grade 1 with pain.
  • Participation in other therapeutic clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial 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): NCT02412228


Locations
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United States, Rhode Island
Memorial Hospital of Rhode Island Withdrawn
Pawtucket, Rhode Island, United States, 02860
Rhode Island Hospital Recruiting
Providence, Rhode Island, United States, 02903
Contact: Kayla Rosati    401-863-3000    kayla_rosati@brown.edu   
Principal Investigator: John Reagan, MD         
The Miriam Hospital Recruiting
Providence, Rhode Island, United States, 02906
Contact: Kayla Rosati    401-863-3000    kayla_rosati@brown.edu   
Principal Investigator: John Reagan, MD         
Sponsors and Collaborators
John Reagan
Rhode Island Hospital
The Miriam Hospital
Memorial Hospital of Rhode Island

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Responsible Party: John Reagan, Principal Investigator: Sponsor-Investigator, Brown University
ClinicalTrials.gov Identifier: NCT02412228     History of Changes
Other Study ID Numbers: 299
First Posted: April 9, 2015    Key Record Dates
Last Update Posted: November 30, 2018
Last Verified: November 2018

Additional relevant MeSH terms:
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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
Dexamethasone acetate
Cyclophosphamide
Ixazomib
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
Antineoplastic Agents, Hormonal