Clinical Trials /

Monitoring, Detoxifying, and Rebalancing Metals During Front Line Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Therapy

NCT03630991

Description:

If you are reading and signing this form on behalf of a potential participant, please note: Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential participant. The goal of this clinical research study is to learn if giving calcium disodium edetate (Ca-EDTA) or dimercaptosuccinic acid (DMSA) to patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) while receiving standard chemotherapy can help to lower the level of metals found in the bone marrow and blood. Researchers think lowering the level of metals found in the blood/bone marrow may help to control the disease and/or improve response to chemotherapy. Researchers also want to find the highest tolerable dose of Ca-EDTA and DMSA that can be given to AML or MDS patients. The safety of Ca-EDTA and DMSA will also be studied. This is an investigational study. Ca-EDTA and DMSA are both FDA approved and commercially available as metal detoxifiers (medications that lower the amount of metals in the blood). It is considered investigational to give Ca-EDTA and DMSA to patients with AML/MDS who are receiving chemotherapy. Up to 24 participants will be enrolled in this study. All will take part at MD Anderson.

Related Conditions:
  • Acute Myeloid Leukemia
  • Chronic Myeloid Leukemia
  • Myelodysplastic/Myeloproliferative Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Monitoring, Detoxifying, and Rebalancing Metals During Front Line Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Therapy
  • Official Title: Monitoring, Detoxifying, and Rebalancing Metals During Front Line Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Therapy

Clinical Trial IDs

  • ORG STUDY ID: 2017-0752
  • SECONDARY ID: NCI-2018-01610
  • SECONDARY ID: 2017-0752
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03630991

Conditions

  • Acute Myeloid Leukemia
  • Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
  • Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic Syndrome
  • Myelodysplastic/Myeloproliferative Neoplasm
  • Secondary Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
Edetate Calcium DisodiumC10H12CaN2Na2O8, Calcium disodium edetate, Calcium disodium ethylenediaminetetraacetate, Calcium Disodium Versenate, Calcium EDTA, Disodium calcium ethylenediaminetetraacetate, EDTA CalciumCa-EDTA Group
DMSAChemet, Meso 2, 3-Dimercaptosuccinic Acid, SUCCIMERDMSA Group

Purpose

Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential participant. The goal of this clinical research study is to learn if giving calcium disodium edetate (Ca-EDTA) or dimercaptosuccinic acid (DMSA) to patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) while receiving standard chemotherapy can help to lower the level of metals found in the bone marrow and blood. Researchers think lowering the level of metals found in the blood/bone marrow may help to control the disease and/or improve response to chemotherapy. Researchers also want to find the highest tolerable dose of Ca-EDTA and DMSA that can be given to AML or MDS patients. The safety of Ca-EDTA and DMSA will also be studied. This is an investigational study. Ca-EDTA and DMSA are both FDA approved and commercially available as metal detoxifiers (medications that lower the amount of metals in the blood). It is considered investigational to give Ca-EDTA and DMSA to patients with AML/MDS who are receiving chemotherapy. Up to 24 participants will be enrolled in this study. All will take part at MD Anderson.

Detailed Description

      Study Groups:

      If you are found to be eligible to take part in this study, the study doctor will assign you
      to receive either Ca-EDTA alone or DMSA alone. This will depend on what the doctor thinks is
      in your best interest and which treatments are available. The study doctor will tell you
      which study drug you are receiving.

      You will be assigned to a dose level of either Ca-EDTA or DMSA based on when you join this
      study. Up to 3 dose levels of Ca-EDTA and DMSA will be tested. About 3-6 participants will be
      enrolled at each dose level. The first group of participants will receive the lowest dose
      level. Each new group will receive a higher dose than the group before it, if no intolerable
      side effects were seen. This will continue until the highest tolerable dose of Ca-EDTA and
      DMSA is found.

      Study Drug Administration:

      You will receive either Ca-EDTA or DMSA during each chemotherapy cycle for up to 6 cycles. A
      cycle is defined as 4 doses of Ca-EDTA or 8 days of DMSA.

      If you are assigned to receive it, you will receive Ca-EDTA by vein over about 30 minutes
      before your dose of chemotherapy.

      If you are assigned to receive it, you will take DMSA by mouth every day for 8 days as
      directed by the study doctor. You will be told when to begin taking the DMSA.

      All participants will also be given a daily multivitamin (which is made up of Vitamins C, E,
      K, B6, and B12 and thiamin, riboflavin, niacin, pantothenic acid, folate, biotin, choline,
      inositol, rubidium, selenium, zinc, and magnesium) and/or standard drugs while you are on
      study. You will take up to 12 multivitamin capsules every day while on study. You may ask the
      study staff for information about how the drugs are given and their risks.

      A central line may be placed to help lower the number of needle sticks needed to draw blood
      and/or give the study drugs and chemotherapy. The study doctor will explain how a central
      line is placed and you may be asked to sign a separate consent form.

      Any missed doses can be made up within a 24-hour time period.

      Length of Study:

      You may receive DMSA or Ca-EDTA for up to 6 cycles. However, your participation in this study
      may end early if your doctor recommends stopping the study treatment sooner. Otherwise, your
      participation in this study will be over after follow-up (described below).

      You will no longer be able to take the study drugs if the disease gets worse, if intolerable
      side effects occur, or if you are unable to follow study directions.

      Study Visits:

      Within 3 days before each cycle:

        -  You will have a physical exam.

        -  Urine will be collected for routine tests.

        -  You will have an EKG.

        -  Blood (about 3 teaspoons) will be drawn to check for certain metals and minerals,
           including the iron levels in your body.

      If you are receiving Ca-EDTA, urine will be collected to check for certain metal levels over
      the 6 hours after your first and last dose of Ca-EDTA.

      On Day 1 of every cycle, blood (about 2 teaspoons) and urine will be collected for routine
      tests. This blood draw will also be used to check for certain metals in your body.

      During Cycle 1, about 30 minutes after your first dose of Ca-EDTA, blood (about 1 teaspoon)
      will be drawn to check for hemolysis (the destruction of red blood cells). Part of this
      sample will also be used to check for certain genetic changes (called P53 folding) that may
      be affected by the level of metal in your body.

      One (1) time between Days 1 and Day 14 of the study, you will complete a questionnaire about
      things that you are exposed to as part of your every day life. It should take about 20-30
      minutes to complete.

      During Cycle 2, part of blood sample collected during routine labs will also be used to check
      for P53 folding.

      On Day 17 of every cycle, blood (about 2-3 teaspoons) will be drawn to check how much metal
      are in the blood.

      You will have a bone marrow aspirate and/or biopsy and blood (about 2-3 teaspoons) drawn at
      Months 1, 3, and 6 to check the status of the disease and to check levels of certain metals.
      The study doctor will discuss this schedule with you. Part of these bone marrow
      biopsy/aspirate sample and/or blood samples will be used for genetic testing in the future as
      part of this study. Researchers want to link genetic changes with the amount of metal found
      in the bone marrow and/or blood samples.

      If you have these tests/procedures scheduled as part of your routine care, you may be able to
      have these blood draws and/or bone marrow biopsies/aspirations performed at the same time.
      Additionally, if these tests/procedures are performed as part of your standard care and
      leftover samples are available, those samples may be collected for testing described in this
      consent form.

      Follow-Up:

      After you complete 6 cycles of DMSA or Ca-EDTA, you will be followed as part of your routine
      care. Once you are off active treatment, information about how you are doing will be
      collected from your medical record every 3-12 months for up to 10 years. If information is
      unavailable in your medical chart, the research staff may call you to collect this
      information. If you are called, it should last about 5 minutes.

      You may be asked to enroll in a separate long-term follow-up study. The study staff will give
      you a separate consent form for that follow-up study which explains the expected procedures
      in more detail.

      About 30 days (+/-1 week) after completion of all study drugs, your safety will be checked
      either by a telephone call or during a clinic visit.
    

Trial Arms

NameTypeDescriptionInterventions
Ca-EDTA GroupExperimentalParticipants receive Ca-EDTA by vein over about 30 minutes before dose of chemotherapy. Participants given a daily multivitamin (which is made up of Vitamins C, E, K, B6, and B12 and thiamin, riboflavin, niacin, pantothenic acid, folate, biotin, choline, inositol, rubidium, selenium, zinc, and magnesium) and/or standard drugs while on study. Participants take up to 12 multivitamin capsules every day while on study.
  • Edetate Calcium Disodium
DMSA GroupExperimentalParticipants take DMSA by mouth every day for 8 days as directed by the study doctor. Participants given a daily multivitamin (which is made up of Vitamins C, E, K, B6, and B12 and thiamin, riboflavin, niacin, pantothenic acid, folate, biotin, choline, inositol, rubidium, selenium, zinc, and magnesium) and/or standard drugs while on study. Participants take up to 12 multivitamin capsules every day while on study.
  • DMSA

Eligibility Criteria

        Inclusion Criteria:

          1. Understand and voluntarily sign an informed consent form.

          2. Age >/= 18 years at the time of signing the informed consent form.

          3. Diagnosis of newly diagnosed or untreated AML with poor-risk cytogenetics, poor-risk
             molecular, or secondary AML (i.e. therapy-related or evolved from antecedent
             hematologic malignancy. Newly diagnosed (or untreated) myeloid blast phase of MPN
             (including myeloid blast phase of CML. Newly diagnosed (or untreated) high-risk,
             very-high risk or secondary MDS. Newly diagnosed (or untreated) MDS/MPN (regardless of
             cytogenetic/molecular status). Relapsed and/or refractory AML, MDS, MDS/MPN, myeloid
             blast phase of MPN (including myeloid blast phase of CML) who are either salvage 1 or
             salvage 2.

          4. Patients on non-investigational regimens or on IND-exempt MD Anderson studies of
             approved drugs are also eligible.

          5. Transformed and untreated AML transformed from previously treated MDS,
             myeloproliferative neoplasm (MPN) or other types of secondary AML are allowed.
             Myeloid-Blast Phase of MPN and Chronic Myeloid Leukemia (CML) are allowed

          6. Eastern Cooperative Oncology Group (ECOG) performance status of </= 2 at study entry

          7. Laboratory test results within these ranges (unless due to leukemia or other
             hematologic malignancy): a) Serum creatinine </= 1.5 mg/dL; b) Total Bilirubin </=2.0
             x upper limit of normal (ULN), unless the patient has Gilbert's; c) AST (SGOT) and/or
             ALT (SGPT) </= 2.0 x ULN.

          8. Women of childbearing potential (WCBP) must have a negative urine pregnancy test
             within 7 days and must either commit to continued abstinence from heterosexual
             intercourse or adopting at least one highly effective method of contraception. These
             methods include intra-uterine device, tubal ligation, partner's vasectomy, and
             hormonal birth control pills. Men must agree not to father a child and agree to use a
             condom if his partner is of child bearing potential.

          9. Extramedullary disease is allowed as long as it can be measured and followed for
             response.

        Exclusion Criteria:

          1. Nursing and pregnant females. Should a woman become pregnant or suspect she is
             pregnant while participating in this study, she should inform her treating physician
             immediately.

          2. Uncontrolled inter-current illness including, but not limited to, uncontrolled active
             infection, symptomatic congestive heart failure, unstable angina pectoris, or
             psychiatric illness/social situations that would limit compliance with study
             requirements or which judged by the investigator, places the patient at unacceptable
             risk.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Cytogenetic response (myelodysplastic syndrome patients)
Time Frame:At 6 months
Safety Issue:
Description:The optimum two-stage design proposed by Simon will be implemented.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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