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

NCT02948283 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 16331NCI-2016-01586
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events as assessed by Common Terminology Criteria for Adverse Events version 4.03

  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.

  Up to 1 year

Secondary Outcomes (7)

• Best overall response

  Up to 1 year

• Clinical benefit response

  Up to 1 year

• Health-Related Quality of Life

  Up to 1 year

• Overall survival

  Up to 1 year

• Progression free survival

  Up to 1 year

Study Arms (1)

Treatment (metformin hydrochloride, ritonavir)

EXPERIMENTAL

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; Drug: Metformin Hydrochloride; Other: Pharmacological Study; Drug: Ritonavir; Other: Quality-of-Life; Other: Questionnaire

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (metformin hydrochloride, ritonavir)

Metformin Hydrochloride DRUG

Given PO

Also known as: Cidophage, Dimefor, Glifage, Glucoformin, Glucophage, Glucophage ER, Metformin HCl, Riomet, Siofor

Treatment (metformin hydrochloride, ritonavir)

Pharmacological Study OTHER

Correlative studies

Treatment (metformin hydrochloride, ritonavir)

Ritonavir DRUG

Given PO

Also known as: Norvir, RIT

Treatment (metformin hydrochloride, ritonavir)

Quality-of-Life OTHER

Ancillary studies

Also known as: Quality of Live

Treatment (metformin hydrochloride, ritonavir)

Questionnaire OTHER

Ancillary studies

Treatment (metformin hydrochloride, ritonavir)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects must have the ability to understand and the willingness to sign a written informed consent
• Life expectancy of \> 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• FOR PATIENTS WITH MULTIPLE MYELOMA (MM):
• Diagnosis of multiple myeloma
• Patients with MM must have measurable disease, defined as one or more of the following:
• Serum M-protein \>= 0.5 g/dL
• Urine M-protein \>= 200 mg/24 hr
• Serum immunoglobulin free light chain (FLC) \>= 100 mg/L (10 mg/dL) and abnormal serum immunoglobulin kappa to lambda FLC ratio
• IgA patients must have serum quantitative immunoglobulin \>= 750 mg/dL
• Patients with oligosecretory or non-secretory disease must have a documented abnormal free light chain ratio (normal value 0.26 to 1.65) or a value beyond the laboratory calculation range
• Disease must be refractory or relapsed after \>= 3 prior regimens (induction therapy and stem cell transplant +/- maintenance will be considered as one regimen)
• FOR PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL):
• Diagnosis of CLL without the following: Richter's transformation, prolymphocytic leukemia (PLL), small lymphocytic lymphoma (SLL)
• Measurable disease, defined as one or more of the following:

You may not qualify if:

• Current or planned use of other investigational agents, or concurrent biological, chemotherapy, or radiation therapy during the study treatment period
• Use of a protease inhibitor for any indication within three months prior to start of study treatment
• Current or planned use of prohibited meds
• Liver disease, except Gilbert's syndrome, liver involvement by CLL or MM, or stable chronic liver disease per investigator's assessment
• Current pancreatitis
• History of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biologic composition to metformin, ritonavir or any of their ingredients
• Non-hematologic malignancy within the past 3 years aside from the following exceptions:
• Adequately treated basal cell or squamous cell skin cancer
• Carcinoma in situ of the cervix
• Prostate cancer \< Gleason grade 6 with a stable prostate-specific antigen test (PSA)
• Successfully treated in situ carcinoma of the breast
• Clinically significant cardiac disease, including:
• \>= Grade 2 myocardial infarction within 6 months prior to day 1 of protocol therapy
• Unstable or uncontrolled disease condition relating to or affecting cardiac function (e.g. unstable angina, congestive heart failure, New York Heart Association Class III-IV) within 6 months prior to day 1 of protocol therapy
• \>= Grade 2 uncontrolled cardiac arrhythmia

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Anemia; Fatigue; Fever; Lymphadenopathy; Lymphocytosis; Leukemia, Lymphocytic, Chronic, B-Cell; Multiple Myeloma; Splenomegaly; Thrombocytopenia; Weight Loss

Interventions

Metformin; Ritonavir; Quality of Life; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Temperature Changes; Lymphatic Diseases; Leukocytosis; Leukocyte Disorders; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hypertrophy; Pathological Conditions, Anatomical; Blood Platelet Disorders; Cytopenia; Body Weight Changes; Body Weight

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Health Status; Demography; Epidemiologic Measurements; Public Health; Environment and Public Health; Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation

Study Officials

• Nitya Nathwani, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2016
• First Posted: October 28, 2016
• Study Start: September 5, 2017
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: February 12, 2021

Record last verified: 2021-02

Locations

US (1)