Metformin Hydrochloride and Ritonavir in Treating Patients With Relapsed or Refractory Multiple Myeloma or Chronic Lymphocytic Leukemia
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|ClinicalTrials.gov Identifier: NCT02948283|
Recruitment Status : Recruiting
First Posted : October 28, 2016
Last Update Posted : September 15, 2017
|Condition or disease||Intervention/treatment||Phase|
|Anemia Fatigue Fever Lymphadenopathy Lymphocytosis Night Sweats Recurrent Chronic Lymphocytic Leukemia Recurrent Plasma Cell Myeloma Refractory Chronic Lymphocytic Leukemia Refractory Plasma Cell Myeloma Splenomegaly Thrombocytopenia Weight Loss||Other: Laboratory Biomarker Analysis Drug: Metformin Hydrochloride Other: Pharmacological Study Drug: Ritonavir Other: Quality-of-Life Other: Questionnaire||Phase 1|
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.
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.
III. To evaluate potential changes in health-related quality of life, as assessed by the Functional Assessment of Cancer Therapy for Multiple Myeloma (FACT-MM) and Leukemia (FACT-Leu).
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Feasibility Study of Metformin/Ritonavir Combination Treatment in Patients With Relapsed/Refractory Multiple Myeloma or Chronic Lymphocytic Leukemia|
|Actual Study Start Date :||September 5, 2017|
|Estimated Primary Completion Date :||September 2018|
|Estimated Study Completion Date :||September 2018|
Experimental: Treatment (metformin hydrochloride, ritonavir)
SINGLE AGENT STAGE : Patients receive metformin hydrochloride PO 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 orally PO BID on days 1-7. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studiesDrug: Metformin Hydrochloride
Other Names:Other: Pharmacological Study
Correlative studiesDrug: Ritonavir
Other Names:Other: Quality-of-Life
Other Name: Quality of LiveOther: Questionnaire
- 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.
- 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).
- Health-Related Quality of Life [ Time Frame: Up to 1 year ]The Functional Assessment of Cancer Therapy for Multiple Myeloma and Leukemia will be scored using published guidelines.
- 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. ]First documented response is defined as stringent complete response, complete response, very good partial response, or partial response.
- 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.
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): NCT02948283
|United States, California|
|City of Hope Medical Center||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Nitya Nathwani, MD 626-256-4673 email@example.com|
|Principal Investigator: Nitya Nathwani, MD|
|Principal Investigator:||Nitya Nathwani, MD||City of Hope Medical Center|