AnemiaPhase 1NCT02948283

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

A Phase 1 study testing Laboratory Biomarker Analysis, Metformin Hydrochloride and Pharmacological Study in people with Anemia and Fatigue, run by City of Hope Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Anemia, Fatigue, Fever
What is being tested?: Laboratory Biomarker Analysis, Metformin Hydrochloride and Pharmacological Study
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 3 participants
Where: 1 siteUnited States
Study dates: 7 Sep 2017to 1 Dec 2017
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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:

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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:
Lymphocytosis >= 5000 in peripheral blood
Measurable lymph nodes > 1.5 cm on palpation and/or computed tomography (CT) scan
Organomegaly by physical exam and/or CT scan
Active disease per International Workshop on Chronic Lymphocytic (IWCLL) 2008 criteria, as defined as one of the following:
Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia
Massive (i.e., at least 6 cm below the left costal margin) or progressive or symptomatic splenomegaly
Massive nodes (i.e., at least 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy
Progressive lymphocytosis with an increase of more than 50 percent over a two-month period or lymphocyte doubling time (LDT) of less than six months; LDT can be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of two weeks over an observation period of two to three months; in patients with initial blood lymphocyte counts of less than 30 x 10^9/L (30,000/L), LDT should not be used as a single parameter to define a treatment indication; in addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (e.g., infection) should be excluded
Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy
Constitutional symptoms, defined as any one or more of the following disease-related symptoms or signs:
Unintentional weight loss of 10 percent or more within the previous six months
Significant fatigue (i.e., ECOG performance scale [PS] 2 or worse; inability to work or perform usual activities)
Fevers higher than 100.5 degrees Fahrenheit (F) or 38.0 degrees Celsius (C) for two or more weeks without other evidence of infection
Night sweats for more than one month without evidence of infection
Received at least 2 prior therapies (regimens) for CLL
In the opinion of the investigator do not require rapid cytoreduction due to bulky disease (e.g. painful lymphadenopathy or organomegaly, or impending end-organ dysfunction
Absolute neutrophil count (ANC) >= 1,000/mm^3
Platelets >= 50,000/mm^3
Aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN)
Alanine aminotransferase (ALT) =< 3 x ULN
Total bilirubin =< 1.5 x ULN; unless presence of Gilbert's syndrome, liver involvement by CLL or MM, or stable chronic liver disease per investigator's assessment
Creatinine clearance of >= 45 mL/min per 24 hour urine collection or the Cockcroft-Gault formula
Woman of childbearing potential (WOCBP): negative urine or serum pregnancy test; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
Corrected QT interval (QTc) =< 480 msec per Fridericia's formula AND PR interval =< 200 msec (using 12-lead electrocardiography [EKG])
Agreement by woman of childbearing potential and sexually active males to use an effective method of contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for three months following duration of study participation
A woman of childbearing potential is defined as a sexually mature woman who:
Has not undergone a hysterectomy or bilateral oophorectomy; or
Has not been naturally postmenopausal for at least 24 consecutive months
FOR PATIENTS WITH MM OR CLL:
At least 2 weeks from prior therapy to time of start of treatment; prior therapy includes steroids (except for =< 10 mg daily prednisone or equivalent which is permitted during the study)

Who cannot join

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

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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
Clinically significant medical disease or condition that, in the investigator's opinion, may interfere with protocol adherence or the patient's ability to give informed consent
Women who are currently or planning to breastfeed during protocol treatment
Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, uncontrolled intercurrent illness etc.
Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Trial locations and contacts

1 site in 1 country.

United States1 site

City of Hope Medical Center
Duarte, California, 91010

Other trials in United States

About this study

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

Read the detailed description

PRIMARY OBJECTIVES:

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:

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).

TERTIARY OBJECTIVES:

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.

Conditions: Anemia, Fatigue, Fever, Lymphadenopathy, Lymphocytosis, Night Sweats
Being tested: Laboratory Biomarker Analysis, Metformin Hydrochloride, Pharmacological Study, Ritonavir, Quality-of-Life
Medical subject headings: Anemia, Fatigue, Fever, Lymphadenopathy, Lymphocytosis, Leukemia, Lymphocytic, Chronic, B-Cell, Multiple Myeloma, Splenomegaly

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Laboratory Biomarker AnalysisOther
Correlative studies
Metformin HydrochlorideDrug
Also called Cidophage, Dimefor, Glifage, Glucoformin
Given PO
Pharmacological StudyOther
Correlative studies
RitonavirDrug
Also called Norvir, RIT
Given PO
Quality-of-LifeOther
Also called Quality of Live
Ancillary studies
QuestionnaireOther
Ancillary studies

Study groups in NCT02948283
Study group	Role	What they receive
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. Receives: Other: Laboratory Biomarker Analysis; Drug: Metformin Hydrochloride; Other: Pharmacological Study; Drug: Ritonavir; Other: Quality-of-Life; Other: Questionnaire

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Up to 1 year

Secondary outcomes (7)

Best overall response
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).
Measured: Up to 1 year
Clinical benefit response
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).
Measured: Up to 1 year
Health-Related Quality of Life
The Functional Assessment of Cancer Therapy for Multiple Myeloma and Leukemia will be scored using published guidelines.
Measured: Up to 1 year
Overall survival
Will be estimated using the product limit method of Kaplan Meier.
Measured: Up to 1 year
Progression free survival
Will be estimated using the product limit method of Kaplan Meier.
Measured: Up to 1 year
Response duration
First documented response is defined as stringent complete response, complete response, very good partial response, or partial response.
Measured: From date of first documented response to documented disease relapse, progression or death, whichever occurs first, assessed up to 1 year.
Time to response
Will be categorized using IMWG. Will be estimated using the product limit method of Kaplan Meier.
Measured: Up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Sep 20171 Dec 2017

First posted28 Oct 2016 (estimated)
Study start7 Sep 2017
Primary completion1 Dec 2017
Study completion1 Dec 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for AnemiaStudies of the same condition, open and under way.
More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 3 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02948283
Sponsor's protocol ID: 16331
Other IDs: NCI-2016-01586, 16331
Status last verified: Oct 2026
First submitted: 26 Oct 2016
Last updated: 19 Oct 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Anemia trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Pilot Feasibility Study of Metformin/Ritonavir Combination Treatment in Patients With Relapsed/Refractory Multiple Myeloma or Chronic Lymphocytic Leukemia
ClinicalTrials.gov ID: NCT02948283
Acronym / sponsor ID: 16331
Conditions: Anemia, Fatigue, Fever, Lymphadenopathy, Lymphocytosis, Night Sweats
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 3 participants (actual)
Lead sponsor: City of Hope Medical CenterUniversity, hospital or other
Collaborators: National Cancer Institute (NCI)
Study start: 7 Sep 2017 (actual)
Primary completion: 1 Dec 2017 (actual)
Study completion: 1 Dec 2017 (actual)
First posted: 28 Oct 2016 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVES:

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:

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).

TERTIARY OBJECTIVES:

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.

After completion of study treatment, patients are followed up at 30 days and then every 28 days.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment (metformin hydrochloride, ritonavir)	Experimental	Other: Laboratory Biomarker Analysis, Drug: Metformin Hydrochloride, Other: Pharmacological Study, Drug: Ritonavir, Other: Quality-of-Life, Other: QuestionnaireSINGLE 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (45 listed)

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
Diagnosis of multiple myeloma
Patients with MM must have measurable disease, defined as one or more of the following:

Key exclusion criteria (19 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Laboratory Biomarker AnalysisCorrelative studies	Other	Treatment (metformin hydrochloride, ritonavir)
Metformin HydrochlorideAlso: Cidophage, Dimefor, Glifage, GlucoforminGiven PO	Drug	Treatment (metformin hydrochloride, ritonavir)
Pharmacological StudyCorrelative studies	Other	Treatment (metformin hydrochloride, ritonavir)
RitonavirAlso: Norvir, RITGiven PO	Drug	Treatment (metformin hydrochloride, ritonavir)
Quality-of-LifeAlso: Quality of LiveAncillary studies	Other	Treatment (metformin hydrochloride, ritonavir)
QuestionnaireAncillary studies	Other	Treatment (metformin hydrochloride, ritonavir)

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.

7 secondary outcomes

Best overall response
Time frame: Up to 1 year
Clinical benefit response
Time frame: Up to 1 year
Health-Related Quality of Life
Time frame: Up to 1 year
Overall survival
Time frame: Up to 1 year
Progression free survival
Time frame: Up to 1 year
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

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2026.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Nitya Nathwani, MD principal investigator

City of Hope Medical Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 45 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events as assessed by Common Terminology Criteria for Adverse Events version 4.03 (time frame: Up to 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02948283.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2026.