AzTrials
AzTrials

Adult Acute Megakaryoblastic Leukemia (M7)Phase 1NCT01820624

Lithium Carbonate and Tretinoin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

A Phase 1 study testing tretinoin, lithium carbonate and laboratory biomarker analysis in people with Adult Acute Megakaryoblastic Leukemia (M7) and Adult Acute Monoblastic Leukemia (M5a), run by Paolo Caimi, MD 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
Search all trials

Trial summary

This phase I trial studies the side effects and best dose of tretinoin when given together with lithium carbonate in treating patients with relapsed or refractory acute myeloid leukemia. Lithium carbonate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
tretinoin, lithium carbonate and laboratory biomarker analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteUnited States
Study dates
30 Apr 2013to 13 Nov 2015
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

  • Patients must have histologically or cytologically confirmed non-acute promyelocytic leukemia (APL) acute myeloid leukemia (AML)
  • AML patients must either:
  • Be ineligible to receive standard intensive induction chemotherapy (based upon judgement of the treating physician, based on parameters such as comorbidities, cytogenetic studies as well as), or
  • Have relapsed or refractory disease to previous chemotherapy (induction and/or consolidation) for acute myeloid leukemia; patients must have recovered from acute toxicities of AML chemotherapy
  • Prior treatment for pre-existing hematologic conditions is allowed and includes hydroxyurea, thalidomide, hematopoietic growth factors, Zarnestra, lenalidomide, arsenic trioxide, imatinib, corticosteroids, histone deacetylase inhibitors, azacytidine, midostaurin sorafenib or other targeted agents. Use of hydroxyurea for control of blast counts is allowed during the trial.
  • A minimum of 4 weeks must have elapsed since the administration of all other investigational agents
Show all 15Show fewer
  • A minimum of 5 days must have elapsed since the administration of hematopoietic growth factors with short half life (filgrastim, erythropoietin), while for longer - acting hematopoietic growth factors, the minimum time elapsed is 20 days
  • Performance status Eastern Cooperative Oncology Group (ECOG) 0 - 2
  • Life expectancy of > 12 weeks, in the opinion of and as documented by the investigator
  • Total bilirubin ≤ 1.5 times the institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 X institutional upper limit of normal
  • Serum creatinine ≤ 1.5 the institutional upper limit of normal
  • There is no exclusion for the presence of cytopenias
  • The effects of tretinoin and lithium on the developing human fetus are unknown; for this reason and because retinoid agents as well as other therapeutic agents used in this study are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (double barrier method of birth control or abstinence) from the time of study entry, for the duration of study participation and for 3 months after completing treatment; should a woman become pregnant or suspect that she is pregnant while she or her partner is participating in this study, she should inform the treating physician immediately
  • Subjects must have the ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Prior treatment toxicities must be resolved to ≤ grade 1 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0
  • Patients who are currently receiving any other investigational agents
  • Patients with untreated central nervous system involvement by AML should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; this is an uncommon situation in AML and therefore a lumbar puncture for cerebrospinal fluid (CSF) sampling or magnetic resonance imaging (MRI) imaging are Not necessary to rule out central nervous system (CNS) involvement in the absence of clinical suspicion by the treating physician
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to tretinoin or lithium carbonate or other agents used in this study
  • Prohibited medications, supplements and herbal medications:
  • Tetracycline and its derivatives (enhance the risk of retinoic acid toxicity)
Show all 20Show fewer
  • Live vaccines
  • Vitamin A
  • St. John's wort
  • Dong quai: Herbal supplement, (Angelica sinensis)
  • Cytochrome P450 2C8 (CYP2C8) inhibitors: gemfibrozil, trimethoprim, thiazolinediones, montelukast, quercetin
  • CYP2C8 inducers: rifampicin
  • Patients receiving any medications or substances that are moderate and strong inhibitors of CYP2C8 or inducers of CYP2C8 are ineligible
  • Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant or breastfeeding women are excluded from this study because tretinoin is a retinoid derivative agent with the potential for teratogenic or abortifacient effects; because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with tretinoin, breastfeeding should be discontinued if the mother is treated with tretinoin; these potential risks may also apply to other agents used in this study
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with tretinoin; in addition, these patients are at increased risk of lethal infections when treated with marrow suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  • Chronic active hepatitis B or C infection
  • Previous diagnosis of bipolar disorder
  • Known hypersensitivity to lithium or tretinoin
  • Personal or family history of established Brugada syndrome; if pre-enrollment electrocardiogram (ECG) demonstrates abnormal findings (ST elevation in precordial leads), cardiology consultation should be obtained to rule out presence of this inherited syndrome; patients with family history of unexplained sudden death before the age 45 years; personal history of unexplained syncope or history of unexplained ventricular tachycardia or fibrillation should have a cardiology evaluation to rule out the diagnosis of Brugada syndrome

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44106

Other trials in United States

About this study

Official title: Phase I Trial of Lithium and Tretinoin for Treatment of Non-Promyelocytic Acute Myeloid Leukemia in Patients Intolerant or Relapsed/Refractory to Standard Chemotherapy.

This phase I trial studies the side effects and best dose of tretinoin when given together with lithium carbonate in treating patients with relapsed or refractory acute myeloid leukemia. Lithium carbonate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Tretinoin may help [type of cancer] cells become more like normal cells, and to grow and spread more slowly. Giving lithium carbonate together with tretinoin may kill more cancer cells

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the safety and maximum tolerated dose of the combination of tretinoin with lithium carbonate in subjects with non promyelocytic acute myeloid leukemia.

SECONDARY OBJECTIVES:

  1. To describe the dose limiting toxicities associated with the combination of lithium (lithium carbonate) and tretinoin.

II. To determine the ability of lithium to inhibit glycogen synthase kinase-3 (GSK3) activity in circulating acute myeloid leukemia (AML) cells and to enhance the retinoic acid receptor expression.

III. To determine the ability of lithium and tretinoin to induce differentiation and/or growth inhibition of AML cells.

IV. To determine the response rate of acute myeloid treatment to treatment with the combination of Tretinoin and Lithium.

OUTLINE: This is a dose-escalation study of tretinoin.

Patients receive tretinoin orally (PO) every 12 hours on days 1-7 and 15-21 and lithium carbonate PO three times daily (TID) on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Being tested
tretinoin, lithium carbonate, laboratory biomarker analysis
Medical subject headings
Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute, Leukemia, Erythroblastic, Acute

What participants receive

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

  • tretinoinDrug

    Also called ATRA, Retin-A, TRA

    Given PO

  • lithium carbonateDrug

    Also called Eskalith, Lithium, Lithobid, Lithonate

    Given PO

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT01820624
Study groupRoleWhat they receive
Treatment (tretinoin, lithium carbonate)ExperimentalPatients receive tretinoin PO every 12 hours on days 1-7 and 15-21 and lithium carbonate PO TID on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: tretinoin; Drug: lithium carbonate; Other: laboratory biomarker analysis

What is being measured

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

  1. Maximum tolerated dose of tretinoin when given together with lithium carbonate, defined as the dose level immediately below that at which at least 2/6 subjects experience dose-limiting toxicity (DLT), graded using the NCI CTCAE version 4.0

    Measured: Up to 28 days

Timeline

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

  1. First posted29 Mar 2013 (estimated)
  2. Study start30 Apr 2013
  3. Primary completion9 Oct 2015
  4. Study completion13 Nov 2015

Resources

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
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01820624
Sponsor's protocol ID
CASE3912
Other IDs
NCI-2013-00600
Status last verified
Apr 2017
First submitted
26 Mar 2013
Last updated
27 Apr 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Ueda M, Stefan T, Stetson L, Ignatz-Hoover JJ, Tomlinson B, Creger RJ, Cooper B, Lazarus HM, de Lima M, Wald DN, Caimi PF. Phase I Trial of Lithium and Tretinoin for Treatment of Relapsed and Refractory Non-promyelocytic Acute Myeloid Leukemia. Front Oncol. 2020 Mar 10;10:327. doi: 10.3389/fonc.2020.00327. eCollection 2020.

    PubMed 32211336

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing tretinoin, lithium carbonate and laboratory biomarker analysis in people with Adult Acute Megakaryoblastic Leukemia (M7) and Adult Acute Monoblastic Leukemia (M5a), run by Paolo Caimi, MD 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 15 inclusion and 20 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 27 Apr 2017. 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?

Maximum tolerated dose of tretinoin when given together with lithium carbonate, defined as the dose level immediately below that at which at least 2/6 subjects experience dose-limiting toxicity (DLT), graded using the NCI CTCAE version 4.0 (time frame: Up to 28 days). 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 NCT01820624, which also lists 1 linked publication.

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 27 Apr 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in