Chelation Therapy for Acute Myeloid Leukemia

Overseen By Maro Ohanian

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Pregnancy, Uncontrolled infection, Congestive heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 24-36 weeks

58 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, edetate calcium disodium (a chelation therapy) and succimer, to determine their effectiveness for people with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) during chemotherapy. The goal is to assess whether these treatments can reduce metal levels in the body, potentially improving chemotherapy outcomes and controlling the disease. People with AML or MDS who are starting or already undergoing chemotherapy might be suitable candidates, especially if their condition is newly diagnosed or hasn't responded well to previous treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative therapy.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that patients on non-investigational regimens or on certain studies of approved drugs are eligible, suggesting you might be able to continue some medications. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study showed that edetate calcium disodium helps with lead poisoning by lowering lead levels in the body. However, it can cause serious side effects, including potential harm, though these are rare in adults.

Research shows that succimer is generally safe and effective at reducing lead levels in the brain. No reports of overdoses in humans exist, and it has shown low toxicity in animal studies.

Both treatments are in early testing stages for acute myeloid leukemia, so their safety is still being evaluated. This phase mainly focuses on finding the safest dose and understanding side effects. While succimer seems to have a good safety record, the potential for serious side effects with edetate calcium disodium requires close monitoring. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using chelation therapy for acute myeloid leukemia (AML) because it introduces a novel approach to treatment. Unlike the typical chemotherapy regimens like cytarabine and daunorubicin, this therapy uses agents such as edetate calcium disodium and succimer to remove excess metals from the body, which may influence cancer cell survival. Edetate calcium disodium is administered intravenously, while succimer is taken orally, offering flexibility in treatment administration. This new mechanism of action, targeting metal ions, provides a fresh angle in combating AML, potentially reducing toxicity and improving outcomes compared to conventional chemotherapy alone.

What evidence suggests that edetate calcium disodium or succimer might be an effective treatment for acute myeloid leukemia?

Research suggests that edetate calcium disodium and succimer, both under study in this trial, might help treat acute myeloid leukemia (AML) by reducing metal levels in the blood and bone marrow. This reduction could help manage the disease and enhance chemotherapy effectiveness. Participants in one arm of this trial will receive edetate calcium disodium, which has been proven to treat lead poisoning, though no direct evidence yet supports its use in cancers like AML. Meanwhile, participants in another arm will receive succimer, used to remove metals from the body, but its effectiveness specifically for AML remains under investigation. Scientists believe that lowering metal levels might prevent cancer cells from growing, though more research is needed to confirm this. ^{1 5 6 7 8}

Who Is on the Research Team?

Maro Ohanian

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed or untreated acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), including high-risk cases and those that have evolved from other conditions. Participants should be in good physical condition, not pregnant, able to consent, and not on certain other clinical trials. They must also agree to use effective contraception.

Inclusion Criteria

Serum creatinine =< 1.5 mg/dL

I have a new or untreated AML diagnosis with high-risk factors.

My AML developed from a previously treated blood disorder.

Exclusion Criteria

I have been diagnosed with Acute Promyelocytic Leukemia.

I do not have any uncontrolled illnesses.

I am currently pregnant or nursing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive edetate calcium disodium or succimer during standard chemotherapy for up to 6 cycles

24-36 weeks

Multiple visits per cycle

Dose Expansion

Patients receive Ca-EDTA and DMSA during standard chemotherapy for up to 6 cycles

24-36 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years

Every 3-12 months

What Are the Treatments Tested in This Trial?

Interventions

• Edetate Calcium Disodium
• Succimer

Trial Overview The trial is testing the safety and optimal dosing of edetate calcium disodium or succimer in patients undergoing chemotherapy for AML or MDS. These agents may reduce metal levels in the body which could help control the disease and improve chemotherapy response.

How Is the Trial Designed?

Group I: Cohort II (succimer, multivitamin) Experimental Treatment 2 Interventions

During standard of care chemotherapy, patients receive succimer PO daily for 8 or 21 days of each cycle beginning day 1. Treatment continues for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive up to 12 multivitamin capsules PO daily while on study. DOSE EXPANSION: During standard of care chemotherapy, patients receive edetate calcium disodium IV daily over 30 minutes for 4 doses for each cycle. DMSA daily for 21 days. Multivitamin capsules daily while on study. Patients will receive treatment for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Cohort I (edetate calcium disodium, multivitamin) Experimental Treatment 2 Interventions

During standard of care chemotherapy, patients receive edetate calcium disodium IV daily over 30 minutes for 4 doses for each cycle. Treatment continues for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive up to 12 multivitamin capsules PO daily while on study. DOSE EXPANSION: During standard of care chemotherapy, patients receive edetate calcium disodium IV daily over 30 minutes for 4 doses for each cycle. DMSA daily for 21 days. Multivitamin capsules daily while on study. Patients will receive treatment for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

Both sodium calcium edetate and DMSA (succimer) are effective treatments for inorganic lead poisoning, with similar efficacy in enhancing lead excretion, but no definitive evidence that one is superior to the other based on current studies.

Sodium calcium edetate is administered parenterally and is more effective at reducing lead concentrations in bone, while DMSA, which is taken orally, is better at reducing lead levels in the kidneys; both treatments have notable adverse effects, including nephrotoxicity and mineral depletion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of sodium calcium edetate (edetate calcium disodium) and succimer (DMSA) in the treatment of inorganic lead poisoning. Bradberry, S., Vale, A.[2015]

Chelating agents are effective in treating lead poisoning by binding lead in the body and enhancing its excretion, but they can also lead to serious side effects, such as hypocalcemia, which has been linked to cardiac arrest in some cases.

Due to the risks associated with certain chelating agents like Na2EDTA, especially in children, healthcare providers are advised to consult experts and consider safer alternatives for lead poisoning treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deaths associated with hypocalcemia from chelation therapy--Texas, Pennsylvania, and Oregon, 2003-2005. [2013]

Chelation therapy using agents like DMPS and DMSA is effective for treating acute arsenic and mercury poisoning, with studies showing they enhance the excretion of these heavy metals when administered quickly after exposure.

While DMPS and DMSA are safer alternatives to the older chelator BAL, their effectiveness in treating chronic heavy metal exposure remains uncertain, as the benefits in reducing long-term health risks are not well established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of chelation in the treatment of arsenic and mercury poisoning. Kosnett, MJ.[2021]

Both dimercaptopropanol (BAL) combined with EDTA and orally administered meso-2,3-dimercaptosuccinic acid (DMSA) with EDTA effectively reduced blood lead levels in children with lead poisoning, showing significant decreases from pretreatment values over time.

However, the BAL + EDTA treatment was associated with more frequent side effects, such as elevated liver enzymes and vomiting, compared to the DMSA + EDTA treatment, suggesting that DMSA may be a safer option for chelation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of dimercaptosuccinic acid and calcium disodium ethylenediaminetetraacetic acid versus dimercaptopropanol and ethylenediaminetetraacetic acid in children with lead poisoning. Besunder, JB., Super, DM., Anderson, RL.[2019]

TACT2 is a large clinical trial involving 1000 patients with diabetes and a history of myocardial infarction, testing the effects of 40 weekly infusions of edetate disodium on cardiovascular events over a follow-up period of 2.5 to 5 years.

The trial aims to confirm previous findings that chelation therapy can reduce cardiovascular events, with a focus on understanding whether the benefits are linked to the removal of toxic metals like lead and cadmium from the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The trial to assess chelation therapy 2 (TACT2): Rationale and design. Lamas, GA., Anstrom, KJ., Navas-Acien, A., et al.[2023]

Oral DMSA (30 mg/kg/day) significantly increased urine lead excretion and reduced blood lead concentrations in adults with high blood lead levels, demonstrating its efficacy as a treatment for lead poisoning.

DMSA was generally well tolerated, with most patients experiencing improvement in symptoms like headache and lethargy within two days, although there were some adverse effects, including a severe reaction in one case.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of oral dimercaptosuccinic acid (succimer) in adult patients with inorganic lead poisoning. Bradberry, S., Sheehan, T., Vale, A.[2013]

In a study of 633 patients with diabetes who had previously experienced a heart attack, treatment with edetate disodium significantly reduced the risk of serious cardiovascular events compared to placebo, with a hazard ratio of 0.59, indicating a 41% lower risk.

Patients on insulin therapy showed the greatest benefit from edetate disodium treatment, with a 58% reduction in the primary endpoint of cardiovascular events compared to those receiving placebo, suggesting that insulin users may respond better to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible differential benefits of edetate disodium in post-myocardial infarction patients with diabetes treated with different hypoglycemic strategies in the Trial to Assess Chelation Therapy (TACT). Escolar, E., Ujueta, F., Kim, H., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03630991

NCT03630991 | Edetate Calcium Disodium or Succimer in ... Edetate calcium disodium or succimer may help to lower the level of metals found in the bone marrow and blood and may help to control the disease and/or improve ...

2. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03630991/

Clinical Trial: NCT03630991 This phase I trial studies the side effects and best dose of edetate calcium disodium or succimer in treating patients with acute myeloid ...

3. withpower.com withpower.com/trial/phase-1-neoplasms-9-2018-86260

Chelation Therapy for Acute Myeloid Leukemia There is no direct evidence supporting the effectiveness of Edetate Calcium Disodium for treating acute myeloid leukemia, but it has been used to reduce lead ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2018-01610

Edetate Calcium Disodium or Succimer in Treating Patients ... Edetate calcium disodium or succimer may help to lower the level of metals found in the bone marrow and blood and may help to control the disease and/or improve ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03630991?term=SUCCIMER&viewType=Table&rank=3

Edetate Calcium Disodium or Succimer in Treating Patients ... A group of independent scientists who monitor the safety and scientific integrity of a clinical trial. The DMC can recommend to the sponsor that the trial be ...

6. valudor.com valudor.com/wp-content/uploads/2024/04/Ca-EDTA.pdf

Safety Data Sheet: Sodium calcium edetate For non-emergency personnel. Ventilate affected area. Avoid contact with eyes. Avoid breathing dust. Control of dust. Wearing of suitable protective ...

7. go.drugbank.com go.drugbank.com/drugs/DB14598

Edetate calcium disodium Edetate calcium disodium is indicated to reduce blood levels and depot stores of lead in acute and chronic lead poisoning.

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2009/008922s016lbl.pdf

Calcium Disodium Versenate WARNINGS: Calcium Disodium Versenate is capable of producing toxic effects which can be fatal. Lead encephalopathy is relatively rare in adults, ...