Clinical Trial: Metformin Hydrochloride and Ritonavir in Treating Patients With Relapsed or Refractory Multiple Myeloma or Chronic Lymphocytic Leukemia

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

Official Title: A Pilot Feasibility Study of Metformin/Ritonavir Combination Treatment in Patients With Relapsed/Refractory Multiple Myeloma or Chronic Lymphocytic Leukemia

Brief Summary: This pilot clinical trial studies the side effects and best dose of metformin hydrochloride and ritonavir in treating patients with multiple myeloma or chronic lymphocytic leukemia that has returned after a period of improvement or has not responded to treatment. Metformin hydrochloride and ritonavir may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To assess the safety, tolerability and feasibility of administering metformin hydrochloride (metformin)/ritonavir combination therapy in patients with relapsed/refractory multiple myeloma or relapsed/refractory chronic lymphocytic leukemia.

SECONDARY OBJECTIVES:

I. To characterize the clinical activity of this two-drug combination by assessing disease response, response duration, and (in relapsed/refractory multiple myeloma [RRMM]) clinical benefit response.

II. To assess the progression-free survival, overall survival and compliance of all patients who start the two-drug combination.

TERTIARY OBJECTIVES:

I. To describe the plasma pharmacokinetics of metformin and ritonavir when given in combination.

II. In relapsed/refractory chronic lymphocytic leukemia (RRCLL), to describe changes in pAKT, pAMPK, and MCL-1, in circulating lymphocytes in response to treatment.

OUTLINE: This is a dose escalation study.

SINGLE AGENT STAGE: Patients receive metformin hydrochloride orally (PO) twice daily (BID) on days 1-7 in the absence of disease progression or unacceptable toxicity.

COMBINATION REGIMEN STAGE: Patients receive metformin hydrochloride PO BID and ritonavir PO BID on days 1-7. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 28 days
Sponsor: City of Hope Medical Center

Current Primary Outcome: Incidence of adverse events as assessed by Common Terminology Criteria for Adverse Events version 4.03 [ Time Frame: Up to 1 year ]

Observed toxicities will be summarized, for all patients based on highest achievable dose, in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Best overall response [ Time Frame: Up to 1 year ]
    Will be categorized using International Myeloma Working Group (IMWG). Will be calculated, for the initial and sub-analysis for all dose levels; Copper Pearson binomial 95% confidence intervals will be calculated for these estimates. Will be evaluated based on number/type of prior therapy(ies).
  • Clinical benefit response [ Time Frame: Up to 1 year ]
    Will be categorized using IMWG. Clopper Pearson binomial 95% confidence intervals will be calculated. Will be evaluated based on number/type of prior therapy(ies).
  • Overall survival [ Time Frame: Up to 1 year ]
    Will be estimated using the product limit method of Kaplan Meier.
  • Progression free survival [ Time Frame: Up to 1 year ]
    Will be estimated using the product limit method of Kaplan Meier.
  • Response duration [ Time Frame: From date of first documented response to documented disease relapse, progression or death, whichever occurs first, assessed up to 1 year. ]
  • Time to response [ Time Frame: Up to 1 year ]
    Will be categorized using IMWG. Will be estimated using the product limit method of Kaplan Meier.


Original Secondary Outcome: Same as current

Information By: City of Hope Medical Center

Dates:
Date Received: October 26, 2016
Date Started: March 8, 2017
Date Completion: September 2018
Last Updated: March 22, 2017
Last Verified: March 2017