Clinical Trials /

Determining the Feasibility of MLN9708 as Maintenance After Allogeneic Stem Cell Transplant for Multiple Myeloma

NCT02168101

Description:

The purpose of the study is to determine whether MLN9708 is effective as maintenance therapy following allogeneic stem cell transplant in patients with high-risk multiple myeloma.

Related Conditions:
  • Multiple Myeloma
  • Plasma Cell Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Determining the Feasibility of MLN9708 as Maintenance After Allogeneic Stem Cell Transplant for Multiple Myeloma
  • Official Title: Open-Label Study to Determine the Feasibility of MLN9708 as Maintenance After Allogeneic Stem Cell Transplant for Multiple Myeloma, Followed by an Expansion Phase at the Maximum-Tolerated Dose (MTD) - A Phase II Study

Clinical Trial IDs

  • ORG STUDY ID: SCRI MM 42
  • NCT ID: NCT02168101

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
MLN9708ixazomibMLN9708

Purpose

The purpose of the study is to determine whether MLN9708 is effective as maintenance therapy following allogeneic stem cell transplant in patients with high-risk multiple myeloma.

Detailed Description

      Although multiple myeloma is considered fatal, survival has dramatically improved over the
      last two decades with the introduction of more effective treatment options. Proteasome
      inhibitors have an anti-myeloma effect and are often used as either initial treatment or at
      relapse in patients with multiple myeloma. MLN9708 is an orally bioavailable, potent,
      reversible inhibitor of the 20S proteasome. Phase I studies have shown MLN9708 to be very
      well tolerated with minimal peripheral neuropathy. It has also shown impressive anti-myeloma
      activity in both the relapsed/refractory setting and the upfront setting (Kumar et al. 2011,
      Berdeja et al. 2011, Richardson et al. 2011). These characteristics make MLN9708 an ideal
      proteasome inhibitor to use after allogeneic stem cell transplant. In this Phase II,
      open-label, multicenter, non-randomized study the investigators will investigate the role of
      MLN9708 as maintenance after allogeneic stem cell transplant in patients with high-risk
      multiple myeloma, and in patients with multiple myeloma who have relapsed after an autologous
      stem cell transplant.
    

Trial Arms

NameTypeDescriptionInterventions
MLN9708ExperimentalPatients will be enrolled between Days 45 and 120 after allogeneic transplant and will receive MLN9708 on Days 1, 8, and 15 of each 28-day cycle for 6 cycles. Up to 18 patients will be enrolled in a dose-escalation phase to determine the maximum tolerated dose (MTD). Once the MTD is determined, an additional 20 patients will be enrolled in an expansion phase at that dose. Dose-Escalation Phase: MLN9708 will be administered orally (PO) as monotherapy. Dosing will start at 2.3 mg. If acceptable tolerability is demonstrated, escalations will be made to 3 mg and to a maximum-planned dose (MPD) of 4 mg. Expansion Phase: An additional 20 patients will be enrolled between Days 45 and 120 after allogeneic transplant and will receive MLN9708 orally on Days 1, 8, and 15 of each 28-day cycle for 6 cycles.
  • MLN9708

Eligibility Criteria

        Inclusion Criteria:

        KEY POINTS:

          1. Symptomatic multiple myeloma or asymptomatic myeloma with myeloma-related organ damage
             diagnosed according to standard criteria in patients who received allogeneic
             transplant due to high-risk prognostic features, such as, but not limited to:

               -  Chromosome 17p, partial deletion [del(17p)], t(4;14), t(14;16), t(14;20)

               -  Plasma cell leukemia

               -  PFS of less than 2 years after autologous stem cell transplant

          2. Evidence of engraftment of neutrophils (absolute neutrophil count [ANC] >1000
             cells/mm3) and platelets (platelets >60,000 cells/mm3) [dose escalation phase] and
             >50,000 cells/mm3 [dose expansion phase]).

          3. Achievement of at least a PR prior to allogeneic stem cell transplant

          4. Adequate liver and kidney function

          5. Ability to swallow oral medication

          6. Absence of gastrointestinal symptoms that precludes oral intake and absorption of
             MLN9708

          7. Off antibiotics and amphotericin B formulations, voriconazole or other anti-fungal
             therapy for the treatment of proven, probable or possible infections

          8. ECOG of ≤ 2

          9. Life expectancy ≥3 months

         10. Ability to understand the nature of this study and give written informed consent

        Exclusion Criteria:

          1. Patients with progressive disease when compared to pre-transplant staging as defined
             by IMWG Uniform Response criteria for Multiple Myeloma.

          2. Umbilical cord blood transplant

          3. Patients with > Grade 2 peripheral neuropathy with pain, or ≥ Grade 3 peripheral
             neuropathy per NCI CTCAE Version 4.0

          4. Patients with uncontrolled bacterial, viral, or fungal infections

          5. New York Heart Association (NYHA) Class III or IV heart failure uncontrolled angina,
             severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
             ischemia or active conduction system abnormalities.

          6. Patients who are pregnant or breastfeeding

          7. Most recent chemotherapy ≤21 days and ≤ Grade 1 chemotherapy-related side effects,
             with the exception of alopecia

          8. Use of a study drug ≤21 days or 5 half-lives (whichever is shorter) prior to the first
             dose of MLN9708. For study drugs for which 5 half-lives is ≤21 days, a minimum of 10
             days between termination of the study drug and administration of MLN9708 is required.

          9. Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89)
             administered ≤14 days or limited field radiation for palliation ≤7 days prior to
             starting study drug or has not recovered from side effects of such therapy

         10. Major surgical procedures ≤14 days of beginning study drug, or minor surgical
             procedures ≤7 days. No waiting is required following port-a-cath placement.

         11. Ongoing or active systemic infection. Known diagnosis of human immunodeficiency virus,
             hepatitis B, or hepatitis C

         12. Central Nervous System involvement

         13. Known allergy to any of the study medications, their analogues, or excipients in the
             various formulations of any agent.

         14. Systemic treatment with moderate and strong inhibitors of cytochrome P450 (CYP) 1A2,
             CYP3A, or clinically significant CYP3A inducers, or use of Ginkgo biloba or St. John's
             wort within 14 days before study drug administration in the study.

         15. Presence of other active cancers, or history of treatment for invasive cancer ≤5
             years. Patients with Stage I cancer who have received definitive local treatment and
             are considered unlikely to recur are eligible. All patients with previously treated in
             situ carcinoma (i.e., non-invasive) are eligible, as are patients with history of
             non-melanoma skin cancer.

         16. Graft versus host disease > Grade 2; or GVHD grade 1 or Grade 2 which requires > 0.5
             mg/kg methylprednisolone, or equivalent.

        There are additional Inclusion/Exclusion criteria. The Study Center will determine if you
        meet all criteria and will answer any questions you may have about the trial.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Highest dose at which ≤1 of 6 patients experiences a dose-limiting toxicity (DLT) during one cycle (28 days) of therapy.
Time Frame:Days 1, 4, 8 and 15 of Cycle 1 (28 days)
Safety Issue:
Description:The maximum tolerated dose (MTD) of study drug will be determined as the number of patients experiencing a Grade 3 or Grade 4 adverse event utilizing the National Cancer Institute Common Technology Criteria for Adverse Events (NCI CTCAE) v4.0

Secondary Outcome Measures

Measure:Progression-Free Survival at 2 years post-maintenance therapy
Time Frame:every 8 weeks for approximately 24 weeks then every 3 months thereafter for 2 years
Safety Issue:
Description:Defined as the time from Day 1 of study drug administration to disease progression as defined by International Myeloma Working Group Uniform Response Criteria, or death on study. Patients who discontinue study treatment prior to progression will be followed every 3 months during years 1 and 2 for survival.
Measure:Overall Survival at 2 years post-allogeneic stem cell transplant (ASCT)
Time Frame:every 8 weeks for approximately 24 weeks after ASCT, then every 3 months thereafter for 2 years.
Safety Issue:
Description:Defined as the time from Day 1 of study drug administration to death on study.
Measure:Number of subjects with incidence of graft-versus-host disease (GVHD)
Time Frame:every 28 days, up to 24 months
Safety Issue:
Description:Assessed from date of randomization until date of first documented progression, or date of death from any cause, up to 24 months

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:SCRI Development Innovations, LLC

Trial Keywords

  • MLN9708
  • allogeneic stem cell transplant
  • multiple myeloma
  • ixazomib
  • autologous stem cell transplant

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