Clinical Trial: Ixazomib Citrate, Lenalidomide, and Dexamethasone in Treating Patients With POEMS Syndrome

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Ixazomib, Lenalidomide, and Dexamethasone for Patients With POEMS Syndrome

Brief Summary: This pilot clinical trial studies how well ixazomib citrate, lenalidomide, and dexamethasone work in treating patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as lenalidomide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ixazomib citrate, lenalidomide, and dexamethasone may work better in treating patients with POEMS syndrome.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Normalization of VEGF after 3 cycles of therapy.

SECONDARY OBJECTIVES:

I. Toxicity and safety of the combination of ixazomib citrate (ixazomib), lenalidomide, and dexamethasone.

II. Hematologic response after 3 cycles of therapy. III. Hematologic response rates and/or VEGF response at 12 months. IV. Overall survival.

TERTIARY OBJECTIVES:

I. Improvement of peripheral neuropathy (Overall Neuropathy Limitations Scale [ONLS], Modified Neurological Impairment Score for POEMS [mNIS+7POEMS], and performance score), ascites/effusions, diffusing capacity of the lungs for carbon monoxide (DLCO) after 3 cycles of therapy.

II. Improvement of peripheral neuropathy (ONLS, mNIS+7POEMS, and performance score), ascites/effusions, DLCO, and positron emission tomography (PET)-scan (if abnormal at baseline) at 12 months (both groups) and at 24 and 36 months (group 2 only).

III. Time to VEGF response, hematologic response, and clinical response. IV. Time to VEGF progression, hematologic progression, and clinical progression.

V. Doses delivered will be tabulated to establish tolerance of study drugs. VI. To describe changes in bone biomarkers with treatment of ixazomib, lenalidomide, and dexamethasone.

OUTLINE: Patients are assigned to 1 of 2 groups.

GROUP I: Patients receive ixazomib citrate orally (PO) on days 1, 8, and 15, lenalidomide PO once daily (QD) on days 1-21, and dexam
Sponsor: Mayo Clinic

Current Primary Outcome: Rate of normalization of VEGF defined as VEGF value decreasing to below upper limit of normal (86 pg/mL) [ Time Frame: Up to 3 months ]

In each group, the rate of normalization of VEGF by 3 months (post-3 cycles) will be examined along with the prognostic factors for patients accrued to this study. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent binomial confidence intervals for the true success proportion will be calculated.


Original Primary Outcome: Rate of normalization of VEGF defined as VEGF value decreasing to below ULN (86 pg/mL) [ Time Frame: Up to 3 months ]

In each group, the rate of normalization of VEGF by 3 months (post-3 cycles) will be examined along with the prognostic factors for patients accrued to this study. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent binomial confidence intervals for the true success proportion will be calculated.


Current Secondary Outcome:

  • Hematologic response rate [ Time Frame: Up to 3 months ]
    Hematologic response rate after 3 cycles of therapy (or 3 months after registration) will be estimated by the number of hematologic responses (partial response, very good partial response, or complete response) observed within 3 months of registration divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true hematologic response rate after 3 cycles of therapy (or 3 months after registration) will be calculated.
  • Hematologic response rate [ Time Frame: Up to 12 months ]
    Hematologic response rate after 13 cycles of therapy (or 12 months) will be evaluated. Exact binomial 95% confidence intervals for the true rates at 12 months will be calculated.
  • Incidence of adverse events evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 3 years ]
    The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
  • Normalization of VEGF [ Time Frame: Up to 12 months ]
    Normalization of VEGF after 13 cycles of therapy (or 12 months after registration) will be evaluated. Exact binomial 95% confidence intervals for the true rates at 12 months will be calculated.
  • Survival time [ Time Frame: Time from registration to death due to any cause, assessed up to 3 years ]
    The distribution of survival time will be estimated using the method of Kaplan-Meier.


Original Secondary Outcome:

  • Hematologic response rate [ Time Frame: Up to 3 months ]
    Hematologic response rate after 3 cycles of therapy (or 3 months after registration) will be estimated by the number of hematologic responses (partial response [PR], very good PR, or complete response) observed within 3 months of registration divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true hematologic response rate after 3 cycles of therapy (or 3 months after registration) will be calculated.
  • Hematologic response rate [ Time Frame: Up to 12 months ]
    Hematologic response rate after 13 cycles of therapy (or 12 months) will be evaluated. Exact binomial 95% confidence intervals for the true rates at 12 months will be calculated.
  • Incidence of adverse events evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 3 years ]
    The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
  • Normalization of VEGF [ Time Frame: Up to 12 months ]
    Normalization of VEGF after 13 cycles of therapy (or 12 months after registration) will be evaluated. Exact binomial 95% confidence intervals for the true rates at 12 months will be calculated.
  • Survival time [ Time Frame: Time from registration to death due to any cause, assessed up to 3 years ]
    The distribution of survival time will be estimated using the method of Kaplan-Meier.


Information By: Mayo Clinic

Dates:
Date Received: September 26, 2016
Date Started: October 2016
Date Completion: October 2021
Last Updated: May 9, 2017
Last Verified: January 2017