Clinical Trial: Lenalidomide and Low-Dose Dexamethasone in Patients With Previously Treated Multiple Myeloma and Kidney Dysfunction

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase I/II Study of the Tolerability of Lenalidomide and Low Dose Dexamethasone in Previously Treated Multiple Myeloma Patients With Impaired Renal Function

Brief Summary:

Patients with previously treated multiple myeloma and kidney dysfunction will be treated with lenalidomide and low-dose dexamethasone. Phase I will study the side effects and best dose of lenalidomide when given together with low-dose dexamethasone therapy. After the maximum safe and tolerated dose is found in Phase I, the study will proceed to Phase II. Phase II will study how well the the treatment works in patients with previously treated (relapsed or refractory) multiple myeloma and kidney dysfunction.

Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with dexamethasone may kill more cancer cells. Lenalidomide and dexamethasone may have different effects in patients who have changes in their kidney function.


Detailed Summary:

Multiple Myeloma (MM) affects approximately 20,000 Americans annually and remains an incurable hematologic malignancy characterized by frequent early response followed by universal treatment relapse necessitating multiple sequential therapeutic regimens. Until recently, few effective therapies existed. Several novel agents for MM have now become available including the immunomodulatory drugs thalidomide, lenalidomide, as well as the proteasome inhibitor, bortezomib. Each of these agents is undergoing extensive clinical evaluation in combination with other therapies to produce unprecedented response rates in newly diagnosed and relapsed MM. Lenalidomide has proven to be a highly effective treatment agent, particularly when used in combination with dexamethasone but is renally excreted and little information is available about its use in myeloma patients with impaired kidney function (20% have renal failure at some time after diagnosis). Defining a safe and effective dose of lenalidomide to use is a critical step in MM treatment.

OUTLINE: This is a Phase I, dose-escalation study of lenalidomide followed by a Phase II study. Patients are stratified according to degree of renal dysfunction (moderate [creatinine clearance 30-60 mL/min] vs severe [creatinine clearance <30 mL/min and does not require dialysis] vs end-stage renal disease [creatinine clearance <30 mL/min and requires dialysis]).

Patients receive oral lenalidomide on days 1-21 and low-dose oral dexamethasone 40 mg on days 1, 8, 15, and 22. There is a 7 day rest (days 22-28) from lenalidomide. Each cycle is 28 days and repeated in the absence of disease progression or unacceptable toxicity.

Patients enrolled in the phase II portion of the study will undergo blood sample collection periodically for pharmacokineti
Sponsor: PrECOG, LLC.

Current Primary Outcome:

  • Maximum tolerated dose of lenalidomide (Phase I) [ Time Frame: 15 months ]
    Phase I-Establish the maximum tolerated dose of lenalidomide in each of three groups of myeloma patients with impaired renal function.
  • Assess response rate (Phase II) [ Time Frame: 56 months ]
    Phase II- Assess the efficacy (response rate [CR, sCR, VGPR, PR]) of this combination across the three groups of myeloma patients with impaired renal function.


Original Primary Outcome:

  • Maximum tolerated dose of lenalidomide (Phase I)
  • Toxicity profile as assessed by NCI CTCAE v3.0 (Phase I)
  • Time to any treatment-related toxicity, treatment-related grade 3+ toxicity, and hematologic nadirs (WBC, ANC, and platelet counts) (Phase I)
  • Time to progression and time to treatment failure (Phase I)
  • Proportion of patients with at least partial response (Phase II)


Current Secondary Outcome:

  • Survival time [ Time Frame: 56 months ]
    To describe the overall survival and progression-free survival of myeloma patients with impaired renal function treated with lenalidomide and dexamethasone.
  • Duration of response [ Time Frame: 56 months ]
    To describe the duration of response and time to treatment failure of myeloma patients with impaired renal function treated with lenalidomide and dexamethasone.
  • Safety profile [ Time Frame: 56 months ]
    To evaluate the safety profile of lenalidomide given in combination with weekly dexamethasone in myeloma patients with impaired renal function.
  • Renal function over time [ Time Frame: 56 months ]
    To describe renal function over time and to evaluate the safety profile of a onetime increase in lenalidomide dose at least 2 cycles after start of treatment due to improved renal function.
  • Pharmacokinetics of lenalidomide in impaired renal function [ Time Frame: 56 months ]
    To determine the pharmacokinetics of lenalidomide administration in myeloma patients with impaired renal function (pharmacokinetic analysis will be performed in up to 12 consented Mayo Clinic subjects treated during the Phase II component of the trial (only).


Original Secondary Outcome:

  • Survival time (Phase II)
  • Progression-free survival time (Phase II)
  • Duration of response (Phase II)
  • Time to treatment failure (Phase II)
  • Adverse events (Phase II)


Information By: PrECOG, LLC.

Dates:
Date Received: November 13, 2008
Date Started: January 21, 2009
Date Completion: March 2019
Last Updated: January 23, 2017
Last Verified: January 2017