Metal Detoxification with Ca-EDTA and DMSA with Standard of Care Therapy to Improve Outcomes in Patients with Acute Myeloid Leukemia or Myeloproliferative Neoplasm in Myeloid Blast Phase
This phase II trial tests how well giving metal detoxification with calcium disodium edetate (Ca-EDTA) and dimercaptosuccinic acid (DMSA) during standard of care therapy works to improve patient outcomes comparted to standard of care therapy alone in patients with acute myeloid leukemia or myeloproliferative neoplasm in myeloid blast phase. Ca-EDTA and DMSA are agents that form bonds with metal ions and are used to remove the toxic metals from the body. These metals are stored in the body (such as the bone marrow and blood) for long periods of time because the body does not have a way to eliminate, or get rid of, them. Researchers think lowering the level of metals found in the blood/bone marrow may help to control the growth of cancer cells and/or improve the response to chemotherapy.
Inclusion Criteria
- Understand and voluntarily sign an informed consent form for participants 18 years or older, unless legally authorized representative (LAR) signs where applicable along with any required verbal assents if patients can provide assent
- Age 18 years or older at the time of signing the informed consent form
- Diagnosis of any of the following: * Newly diagnosed (or untreated) AML or newly diagnosed myeloproliferative neoplasm in myeloid blast phase (MPN-BP) (including chronic myeloid leukemia in blast phase [CML-BP]), Philadelphia chromosome positive (Ph+) AML with intermediate-risk or high-risk (by European Leukemia Network [ELN]), or any other intermediate or high-risk AML by ELN * Secondary AML regardless of ELN risk status, however, may not have core binding factor (CBF) [t(8;21) or inv(16)] ** Secondary AML types include: *** Secondary AML evolved from prior untreated myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN), or aplastic anemia *** Therapy-related AML (t-AML) *** AML evolved after prior MDS, MPN, or aplastic anemia after prior therapy for those myeloid bone marrow disorders *** Secondary AML, including blast phase of MPN (MPN-BP) [also, including CML in blast phase (BP of CML) after prior hematologic myeloid bone marrow disease (MDS, MPN, aplastic anemia, CML) (patients may have received treatment for their prior hematologic disorder for their previous bone marrow disorder) * Newly diagnosed (or untreated) myeloid blast phase of MPN (including myeloid blast phase of CML)/Ph+ AML
- Patients can enroll on this study after start of non-investigational induction therapy but must be within first 2 cycles of front-line therapy, as long as not in a complete remission
- 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 myeloid blast phase of chronic myeloid leukemia (CML) are allowed/Ph+ AML are allowed
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
- Serum creatinine ≤ 2.0 mg/dL (unless due to leukemia or other hematologic malignancy)
- Total bilirubin ≤ 2.0 x upper limit of normal (ULN) unless the patient has Gilbert’s (unless due to leukemia or other hematologic malignancy)
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ) ≤ 2.0 x ULN (unless due to leukemia or other hematologic malignancy)
- Women of childbearing potential (WCBP) must have a negative urine or serum pregnancy test within 14 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 childbearing potential
- Extramedullary disease is allowed if it can be measured and followed for response
Exclusion Criteria
- Nursing and pregnant individuals. Should a study participant become pregnant or suspect pregnancy while participating in this study, the study participant should inform their treating physician immediately
- 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
- Acute promyelocytic leukemia (APL)
- Prior venetoclax failure
Additional locations may be listed on ClinicalTrials.gov for NCT06811233.
Locations matching your search criteria
United States
Texas
Houston
PRIMARY OBJECTIVE:
I. To compare event free survival of patients with newly diagnosed (or untreated) secondary, intermediate, and high-risk acute myeloid leukemia (AML) or newly diagnosed myeloproliferative neoplasm in myeloid blast phase (MPN-BP) (including chronic myeloid leukemia in blast phase [CML-BP]) receiving metal detoxification during standard therapy to patients with newly diagnosed (or untreated) secondary, intermediate, and high-risk AML or newly diagnosed MPN-BP (including CML-BP) receiving standard therapy alone.
SECONDARY OBJECTIVES:
I. Compare the remission rates and overall survival rates of patients with newly diagnosed (or untreated) secondary, intermediate, and high-risk AML and newly diagnosed MPN-BP (including CML-BP) receiving metal detoxification during standard therapy to those receiving standard therapy alone.
II. To assess the efficacy information regarding the combined therapy in terms of the overall response rate (ORR) including complete remission (CR), complete remission with partial hematological recovery (CRh), complete remission with incomplete hematologic recovery (CRi), morphologic leukemia free state (MLFS), and partial remission (PR) in patients with newly diagnosed (or untreated) secondary, intermediate, and high-risk AML and newly diagnosed MPN-BP (including CML-BP) receiving metal detoxification during standard therapy and in patients with secondary, intermediate and high-risk AML and newly diagnosed MPN-BP (including CML-BP) receiving standard therapy alone.
III. To compare adverse events of patients with newly diagnosed (or untreated) secondary, intermediate, and high-risk AML and newly diagnosed MPN-BP (including CML-BP) receiving metal detoxification during standard therapy to patients with newly diagnosed (or untreated), secondary, intermediate, and high-risk AML and newly diagnosed MPN-BP (including CML-BP) receiving standard therapy alone.
IV. To assess the complete remission (CR), complete remission with incomplete hematologic recovery (CRi), complete remission with partial hematological recovery (CRh), partial remission (PR), hematologic improvement (HI), morphologic leukemia free state (MLFS) rates, and the overall survival (OS) in AML and MPN-BP patients undergoing cancer therapy combined with succimer (dimercaptosuccinic acid [DMSA]) and edetate calcium disodium (calcium disodium edetate [Ca-EDTA]) and in patients receiving cancer therapy alone.
V. To assess overall survival and event free survival in AML and MPN-BP patients undergoing cancer therapy combined with DMSA and Ca-EDTA and in patients receiving AML therapy alone
VI. To assess remission duration in AML and MPN-BP patients undergoing cancer therapy combined with DMSA and Ca-EDTA and in patients receiving AML therapy alone.
VII. To monitor toxic and essential metal levels during AML therapy combined with DMSA and Ca-EDTA and to evaluate the reduction in metals in the bone marrow and blood of newly diagnosed AML patients undergoing metal detoxification combined with standard AML therapy.
VIII. Correlate metal and copper isotopic abundance ratios of AML patients with clinical data, conventional cytogenetics, extensive next generation sequencing (NGS) (300-gene panel), exposure survey data, and clinical outcome data, and to perform a larger analysis by pooling this data with metal/genomic/survey/outcome data obtained on 2017-0752, 2017-0937 and PA15-0302.
IX. To assess other responses of interest in measurement of effect section.
EXPLORATORY OBJECTIVES:
I. To correlate the degree of metal chelation with the degree of therapeutic response and minimal residual disease (MRD).
II. To correlate changes (degree of metal chelation) in the metals lead, cadmium, mercury, arsenic, copper, and zinc with the therapeutic responses.
III. To correlate changes in the metal risk scores (based on our published metal scoring system) with the therapeutic responses.
IV. Determine correlations between changes in the serum and bone marrow metal levels of cadmium (Cd), lead (Pb), arsenic (As) and mercury (Hg) with changes in cytogenetic profile or gene expression such as TP53 folding/activity status, mutation burden assessed at cycles 1, 3, and 6 of treatment.
V. To collect environmental exposure data on the environmental health assessment survey.
VI. To assess P53 folding or p53 activity before and after the first dose of Ca-EDTA chelation, and after cycles 1, 3, and 6.
VII. To study changes in cytogenetic/molecular data during treatment, as well as, protein expression data (by immunohistochemistry or proteomics), including for transcription factors/tumor suppressors (e.g. TP53 and MYC).
VIII. Compare changes in metals in the blood, bone marrow and urine between baseline and multiple time points after cycles 1, 3, and 6 of treatment.
IX. Determine correlations between changes in the serum and bone marrow metal levels of Cd, Pb, As and Hg with changes in cytogenetic profile or gene expression such as TP53 folding or activity status, mutation burden on NGS assessed after cycles 1, 3, and 6 of treatment.
X. To correlate changes (degree of metal chelation) in the metals lead, cadmium, mercury, arsenic, copper, and zinc with the therapeutic responses.
XI. Compare changes in metals in the blood, bone marrow and urine between baseline and multiple time points after cycles 1, 3, and on cycle 6 for urine or after cycle 6 for blood/bone marrow.
XII. To explore quality of life during treatment in patients receiving metal detoxification or not receiving metal detoxification during AML therapy, at baseline and multiple time points after cycles 1, 3, and on cycle 6.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive Ca-EDTA intravenously (IV) over 1 hour for a total of 4 days, DMSA orally (PO) once daily (QD) for 21 total doses and multivitamin PO three times per day (TID) continuously during each cycle. Patients also receive standard of care (SOC) therapy. Cycles repeat approximately every 28 days based on the standard of care therapy regimen for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsy/aspirate and blood and urine sample collection throughout the study.
ARM II: Patients receive SOC therapy in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsy/aspirate and blood and urine sample collection. Patients undergo bone marrow biopsy/aspirate and blood and urine sample collection throughout the study.
After completion of study treatment, patients are followed up at 30 days and ever 3 to 12 months for 10 years.
Trial PhasePhase II
Trial Typesupportive care
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorMaro Ohanian
- Primary ID2024-1369
- Secondary IDsNCI-2025-00860
- ClinicalTrials.gov IDNCT06811233