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

Related Clinical Trial
Combination Chemotherapy and Dasatinib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Decitabine as Maintenance Therapy After Standard Therapy in Treating Patients With Previously Untreated Acute Myeloid Leukemia Donor Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia in Remission S0432 Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission Combination Chemotherapy With or Without Valspodar in Treating Patients With Previously Untreated Acute Myeloid Leukemia Tipifarnib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia Alvocidib, Cytarabine, and Mitoxantrone in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Bortezomib, Daunorubicin, and Cytarabine in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia Vorinostat and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia Comparing Three Different Combination Chemotherapy Regimens in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed, Previously Untreated Acute Myeloid Leukemia Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Relapsed or Refractory Acute Leukemia AKT Inhibitor MK-2206 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Early Discharge and Outpatients Care in Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia Previously Treated With Intensive Chemotherapy Bortezomib, Mitoxantrone, Etoposide, and Cytarabine in Relapsed or Refractory Acute Myeloid Leukemia Vorinostat, Azacitidine, and Gemtuzumab Ozogamicin for Older Patients With Relapsed or Refractory AML Trebananib With or Without Low-Dose Cytarabine in Treating Patients With Acute Myeloid Leukemia Cholecalciferol in Treating Patients With Acute Myeloid Leukemia Undergoing Intensive Induction Chemotherapy Alvocidib, Cytarabine, and Mitoxantrone Hydrochloride or Cytarabine and Daunorubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Cyclosporine, Pravastatin Sodium, Etoposide, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Metformin+Cytarabine for the Treatment of Relapsed/Refractory AML Arsenic Trioxide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Sirolimus, Idarubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Lithium Carbonate and Tretinoin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Ixazomib (MLN9708) in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Omacetaxine Mepesuccinate, Cytarabine, and Decitabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia CPX-351 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome Lenalidomide and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Choline Magnesium Trisalicylate and Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia AML Therapy With Irradiated Allogeneic Cells Decitabine, Cytarabine, and Daunorubicin Hydrochloride in Treating Patients With Acute Myeloid Leukemia Busulfan, Fludarabine Phosphate, and Anti-Thymocyte Globulin Followed By Donor Stem Cell Transplant and Azacitidine in Treating Patients With High-Risk Myelodysplastic Syndrome and Older Patients With Acute Myeloid Leukemia Azacitidine and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia Tipifarnib in Treating Patients With Acute Myeloid Leukemia in Remission Genetic and Molecular Characteristics of Mexican Adults With Acute Myeloid Leukemia: a Prospective Multicentric Study. Cytarabine With or Without SCH 900776 in Treating Adult Patients With Relapsed Acute Myeloid Leukemia Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia Studying Biomarkers in Samples From Younger Patients With Acute Myeloid Leukemia Central Nervous System (CNS) Involvement in Acute Myeloid Leukemia (AML)

Brief Title

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

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.

Brief 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. 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
    

Detailed Description

      PRIMARY OBJECTIVES:

      I. 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:

      I. 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.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

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


Condition

Adult Acute Megakaryoblastic Leukemia (M7)

Intervention

tretinoin

Study Arms / Comparison Groups

 Treatment (tretinoin, lithium carbonate)
Description:  Patients 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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

12

Start Date

April 30, 2013

Completion Date

November 13, 2015

Primary Completion Date

October 9, 2015

Eligibility Criteria

        Inclusion Criteria:

          -  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

               -  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

        Exclusion Criteria:

          -  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)

               -  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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Paolo Caimi, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01820624

Organization ID

CASE3912

Secondary IDs

NCI-2013-00600

Responsible Party

Sponsor-Investigator

Study Sponsor

Paolo Caimi, MD

Collaborators

 National Cancer Institute (NCI)

Study Sponsor

Paolo Caimi, MD, Principal Investigator, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center


Verification Date

April 2017