Chelation Therapy for Acute Myeloid Leukemia

Overseen by Maro Ohanian

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: M.D. Anderson Cancer Center

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

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial studies if medications that remove metals from the body can help patients with certain types of blood cancer respond better to chemotherapy. It focuses on patients with acute myeloid leukemia or myelodysplastic syndrome. The goal is to see if lowering metal levels can improve treatment outcomes. Iron chelation therapy has been shown to improve survival and quality of life in patients with myelodysplastic syndrome (MDS).

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.

What data supports the effectiveness of the drug Edetate Calcium Disodium for treating 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 levels in the body and has shown benefits in patients with diabetes after a heart attack. ^{1 2 3 4 5}

How does chelation therapy differ from other treatments for acute myeloid leukemia?

Chelation therapy is unique because it involves using agents like edetate disodium to bind and remove heavy metals from the body, which is different from traditional cancer treatments that target cancer cells directly. This approach is novel for acute myeloid leukemia, as it focuses on altering the body's metal balance rather than directly attacking cancer cells. ^{1 3 5 6 7}

Research Team

Maro Ohanian

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Edetate Calcium Disodium (Chelating Agent)
• Succimer (Chelating Agent)

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.

Participant Groups

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+

Dr. Peter WT Pisters

M.D. Anderson Cancer Center

Chief Executive Officer since 2017

MD from University of Western Ontario

Dr. Jeffrey E. Lee

M.D. Anderson Cancer Center

Chief Medical Officer

MD from Stanford University School of Medicine

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. United States pubmed.ncbi.nlm.nih.gov

Comparison of dimercaptosuccinic acid and calcium disodium ethylenediaminetetraacetic acid versus dimercaptopropanol and ethylenediaminetetraacetic acid in children with lead poisoning. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

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

5. United States 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). [2022]

6. England pubmed.ncbi.nlm.nih.gov

Use of oral dimercaptosuccinic acid (succimer) in adult patients with inorganic lead poisoning. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

The trial to assess chelation therapy 2 (TACT2): Rationale and design. [2023]