Adult Acute Megakaryoblastic Leukemia (M7)Phase 1NCT01849276
Metformin+Cytarabine for the Treatment of Relapsed/Refractory AML
A Phase 1 study testing metformin hydrochloride, cytarabine and laboratory biomarker analysis in people with Adult Acute Megakaryoblastic Leukemia (M7) and Adult Acute Minimally Differentiated Myeloid Leukemia (M0), run by Northwestern University at 1 site in United States.
Trial summary
The purpose of the study is to determine if metformin in combination with cytarabine is safe and effective. Participants in this research study have acute myeloid leukemia (AML) that has come back after initial treatment or has not gone away with initial therapy.There is evidence that metformin directly kills leukemia… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a)
- What is being tested?
- metformin hydrochloride, cytarabine and laboratory biomarker analysis
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Mar 2015to 21 Jan 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patients with relapsed/refractory disease must have morphologic proof (from bone marrow aspirate, smears or touch preps of bone marrow biopsy) of AML with >= 10% blasts within two weeks (14 days) prior to initiation of therapy
- All immunophenotype and cytogenetic/molecular groups are eligible for participation except for acute promyelocytic leukemia (APL) (as proven by the presence of promyelocytic leukemia/retinoic acid receptor alpha [PML-RARα])
- Patients must demonstrate one of the following:
- Relapse after first complete remission
- Refractory to conventional induction chemotherapy (failure to respond to 1 or more cycles of daunorubicin and cytarabine) or to re-induction
- Patients with previously untreated AML are candidates if they are unable to receive anthracyclines, and have documented AML with >= 20% blasts within one week prior to enrollment
Show all 20Show fewer
- Patients with chronic myelogenous leukemia (CML) in myeloid blast crisis are eligible if their disease has failed to respond, and/or they are intolerant, to the available tyrosine kinase inhibitors (TKIs)
- Serum total and direct bilirubin =< upper limit of normal (ULN)
- Serum creatinine < 1.4 mg/dl in females and < 1.5 mg/dl in males, and creatinine clearance > 60 mL/min
- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST])/serum glutamic pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< ULN
- Bicarbonate within the normal range of the hospital lab (24-32 mmol/L)
- Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Females of childbearing potential and sexually active males must agree to use an accepted and effective method of contraception while on study
- Childbearing potential is defined as any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- Has NOT undergone a hysterectomy or bilateral oophorectomy; OR
- Has NOT been naturally postmenopausal for at least 12 consecutive months (i.e. has had menses at any time in the preceding 12 consecutive months)
- Patients with a history of central nervous system (CNS) leukemia are eligible if they are not symptomatic from current CNS involvement
- If there is CNS involvement that is known prior to enrollment or identified subsequently, it will be treated accordingly
- Patients may have received therapy for other malignancies, as long as they have completed therapy at least 6 months prior to study entry and be deemed to have a life expectancy of at least 2 years with regard to that malignancy
- All patients must have given signed, informed consent prior to registration on study
Who cannot join
- Patients who have received chemotherapy or radiotherapy within 4 weeks prior to enrollment are NOT eligible for participation
- The exception to this is patients who are refractory to conventional initial induction chemotherapy (=< 2 courses) or to first radiation (1 course); patients must have morphologic proof (from bone marrow aspirate, smears, or touch preps of marrow biopsy) of AML with > 10% blasts within 2 weeks prior to initiation of study therapy; the last dose of cytotoxic therapy (NOT including hydrea, which is allowed) must have been given >= 14 days prior to initiation of study therapy
- Patients with a history of diabetes mellitus (DM) treated with metformin are NOT eligible for participation
- Patients who are pregnant or breast feeding are NOT eligible for participation due to the lack of knowledge regarding the effects of the drugs on the fetus and during breast feeding
- Patients with any intercurrent organ damage or medical problems that would prohibit therapy are NOT eligible for participation
- Patients with any active, uncontrolled infection are NOT eligible for participation
- Patients who are receiving therapy for another active malignancy are NOT eligible for participation
- The exception to this is squamous cell carcinoma or basal cell carcinoma of the skin
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Study of Metformin and Cytarabine for the Treatment of Relapsed/Refractory Acute Myeloid Leukemia
The purpose of the study is to determine if metformin in combination with cytarabine is safe and effective. Participants in this research study have acute myeloid leukemia (AML) that has come back after initial treatment or has not gone away with initial therapy.There is evidence that metformin directly kills leukemia cells. Laboratory data have also shown that combinations of metformin with cytarabine are more efficient than each agent alone in killing leukemia cells in the laboratory.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the maximum tolerated dose (MTD) of metformin (metformin hydrochloride) in combination with cytarabine in relapsed/refractory AML.
II. Define the dose limiting toxicity (DLT) of metformin in combination with cytarabine in relapsed/refractory AML.
SECONDARY OBJECTIVES:
- Remission rate. II. Overall survival (OS). III. Disease-free survival (DFS). IV. Length of remission.
OUTLINE: This is a dose-escalation study of metformin hydrochloride in combination with Cytarabine.
Patients receive metformin hydrochloride orally (PO) twice daily (BID) on days 1-15 and cytarabine intravenously (IV) over 3 hours BID on days 4-10.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 5 years.
- Conditions
- Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1)
- Being tested
- metformin hydrochloride, cytarabine, laboratory biomarker analysis
- Medical subject headings
- Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute, Leukemia, Erythroblastic, Acute, Blast Crisis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
metformin hydrochlorideDrug
Also called Glucophage
Given orally
cytarabineDrug
Also called ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U
Given IV
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (enzyme inhibitor and chemotherapy) | Experimental | Patients receive metformin hydrochloride orally twice a day on days 1-15 and cytarabine IV over 3 hours twice on days 4-10. Receives: Drug: metformin hydrochloride; Drug: cytarabine; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate Toxicity by Assessing the Adverse Events of Metformin and Cytarabine
To determine the maximum tolerated dose (MTD) by assessing the adverse events of metformin in combination with cytarabine in evaluating toxicity. Assessments will occur daily during cytarabine administration and at least twice weekly following treatment until blood count recovery.
Measured: Checked daily during administration of cytarabine and at least 2x weekly following therapy until desired blood counts acheived (maximum 15 days)
Study Treatment Dose Toxicity Will be Evaluated by Measurement of Adverse Events Experienced While on Treatment
Determination of Dose Limiting Toxicity (DLT) as evidenced by adverse events due to toxicity from study treatment. If no DLT is observed, then 3 patients will be enrolled in the next dose escalated cohort. If one DLT is seen in the first 3 patients, then an additional 3 patients will be enrolled at the same dose cohort. If 0-1 in 6 patients experience a DLT this dose will be considered tolerable and the next dose escalated cohort with enroll 3 patients. If 2 or more in 6 patients experience a DLT, the maximum tolerated dose (MTD) will have been exceeded and the next cohort will enroll 3 patients at a reduced dose.
Measured: Checked daily during administration of cytarabine and at least 2x weekly following therapy until desired blood counts acheived (maximum 15 days)
Secondary outcomes (4)
Remission Rate
Patients will be evaluated for remission status in response to therapy.
Measured: Every 3 months for 2 years, and then every 6 months for 5 years post-treatment
Overall Survival
Patients will be followed-up with from the initiation of study treatment until progression of disease or for up to 5 years, whichever comes first.
Measured: Every 3 months for 2 years, and then every 6 months for 5 years post-treatment
Disease-free Survival
Evaluation of Disease-Free Survival will defined as the time from the initiation of study treatment until the time of disease relapse.
Measured: Every 3 months for 2 years, and then every 6 months for 5 years post-treatment
Length of Remission
Patients will be followed-up with to determine Remission length which is defined as the time from attainment of remission to relapse of disease.
Measured: From date of remission of disease to date of relapse (maximum of 5 year follow-up)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2013 (estimated)
- Study start11 Mar 2015
- Primary completion21 Jan 2016
- Study completion21 Jan 2016
Why it stopped: Slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adult Acute Megakaryoblastic Leukemia (M7)Studies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe 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
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jessica Altman, Northwestern University
- Investigators
- Jessica Altman, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01849276
- Sponsor's protocol ID
- NU 11H03
- Other IDs
- NCI-2011-01084, STU00048047
- Status last verified
- Jan 2019
- First submitted
- 6 May 2013
- Last updated
- 31 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Metformin and Cytarabine for the Treatment of Relapsed/Refractory Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT01849276
- Acronym / sponsor ID
- NU 11H03
- Conditions
- Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Study start
- 11 Mar 2015 (actual)
- Primary completion
- 21 Jan 2016 (actual)
- Study completion
- 21 Jan 2016 (actual)
- First posted
- 8 May 2013 (estimated)
- Results
- Posted 13 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to determine if metformin in combination with cytarabine is safe and effective. Participants in this research study have acute myeloid leukemia (AML) that has come back after initial treatment or has not gone away with initial therapy.There is evidence that metformin directly kills leukemia cells. Laboratory data have also shown that combinations of metformin with cytarabine are more efficient than each agent alone in killing leukemia cells in the laboratory.
Detailed description
PRIMARY OBJECTIVES:
- Determine the maximum tolerated dose (MTD) of metformin (metformin hydrochloride) in combination with cytarabine in relapsed/refractory AML.
II. Define the dose limiting toxicity (DLT) of metformin in combination with cytarabine in relapsed/refractory AML.
SECONDARY OBJECTIVES:
- Remission rate. II. Overall survival (OS). III. Disease-free survival (DFS). IV. Length of remission.
OUTLINE: This is a dose-escalation study of metformin hydrochloride in combination with Cytarabine.
Patients receive metformin hydrochloride orally (PO) twice daily (BID) on days 1-15 and cytarabine intravenously (IV) over 3 hours BID on days 4-10.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (enzyme inhibitor and chemotherapy) | Experimental | Drug: metformin hydrochloride, Drug: cytarabine, Other: laboratory biomarker analysisPatients receive metformin hydrochloride orally twice a day on days 1-15 and cytarabine IV over 3 hours twice on days 4-10. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Patients with relapsed/refractory disease must have morphologic proof (from bone marrow aspirate, smears or touch preps of bone marrow biopsy) of AML with >= 10% blasts within two weeks (14 days) prior to initiation of therapy
- Patients must demonstrate one of the following:
- Patients with previously untreated AML are candidates if they are unable to receive anthracyclines, and have documented AML with >= 20% blasts within one week prior to enrollment
- Patients with chronic myelogenous leukemia (CML) in myeloid blast crisis are eligible if their disease has failed to respond, and/or they are intolerant, to the available tyrosine kinase inhibitors (TKIs)
- Serum total and direct bilirubin =< upper limit of normal (ULN)
Key exclusion criteria (8 listed)
- Patients who have received chemotherapy or radiotherapy within 4 weeks prior to enrollment are NOT eligible for participation
- Patients with a history of diabetes mellitus (DM) treated with metformin are NOT eligible for participation
- Patients who are pregnant or breast feeding are NOT eligible for participation due to the lack of knowledge regarding the effects of the drugs on the fetus and during breast feeding
- Patients with any intercurrent organ damage or medical problems that would prohibit therapy are NOT eligible for participation
- Patients with any active, uncontrolled infection are NOT eligible for participation
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 |
|---|---|---|
| metformin hydrochlorideAlso: GlucophageGiven orally | Drug | Treatment (enzyme inhibitor and chemotherapy) |
| cytarabineAlso: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-UGiven IV | Drug | Treatment (enzyme inhibitor and chemotherapy) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (enzyme inhibitor and chemotherapy) |
Primary outcome
Evaluate Toxicity by Assessing the Adverse Events of Metformin and Cytarabine
Time frame: Checked daily during administration of cytarabine and at least 2x weekly following therapy until desired blood counts acheived (maximum 15 days)
To determine the maximum tolerated dose (MTD) by assessing the adverse events of metformin in combination with cytarabine in evaluating toxicity. Assessments will occur daily during cytarabine administration and at least twice weekly following treatment until blood count recovery.
Study Treatment Dose Toxicity Will be Evaluated by Measurement of Adverse Events Experienced While on Treatment
Time frame: Checked daily during administration of cytarabine and at least 2x weekly following therapy until desired blood counts acheived (maximum 15 days)
Determination of Dose Limiting Toxicity (DLT) as evidenced by adverse events due to toxicity from study treatment. If no DLT is observed, then 3 patients will be enrolled in the next dose escalated cohort. If one DLT is seen in the first 3 patients, then an additional 3 patients will be enrolled at the same dose cohort. If 0-1 in 6 patients experience a DLT this dose will be considered tolerable and the next dose escalated cohort with enroll 3 patients. If 2 or more in 6 patients experience a DLT, the maximum tolerated dose (MTD) will have been exceeded and the next cohort will enroll 3 patients at a reduced dose.
4 secondary outcomes
Remission Rate
Time frame: Every 3 months for 2 years, and then every 6 months for 5 years post-treatment
Overall Survival
Time frame: Every 3 months for 2 years, and then every 6 months for 5 years post-treatment
Disease-free Survival
Time frame: Every 3 months for 2 years, and then every 6 months for 5 years post-treatment
Length of Remission
Time frame: From date of remission of disease to date of relapse (maximum of 5 year follow-up)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Jessica Altman, MD principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing metformin hydrochloride, cytarabine and laboratory biomarker analysis in people with Adult Acute Megakaryoblastic Leukemia (M7) and Adult Acute Minimally Differentiated Myeloid Leukemia (M0), run by Northwestern University at 1 site in United States.
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 20 inclusion and 8 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: stopped early, as of the sponsor's last update on 31 Jan 2019. 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?
Yes. Results are posted in the registry (first posted 13 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Evaluate Toxicity by Assessing the Adverse Events of Metformin and Cytarabine (time frame: Checked daily during administration of cytarabine and at least 2x weekly following therapy until desired blood counts acheived (maximum 15 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Jan 2019.