Edetate Calcium Disodium or Succimer in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome Undergoing Chemotherapy

Acute Myeloid Leukemia Clinical Trial

Official title: Monitoring, Detoxifying, and Rebalancing Metals During Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Therapy

Status Recruiting

Clinical Trial Summary

This phase I trial studies the side effects and best dose of edetate calcium disodium or succimer in treating patients with acute myeloid leukemia or myelodysplastic syndrome undergoing chemotherapy. 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 response to chemotherapy.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To establish the maximal tolerated dose (MTD) of Phase 1 in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients undergoing therapy combined with succimer (DMSA) and edetate calcium disodium (Ca-EDTA). (Phase I dose escalation) II. To assess the efficacy information regarding the combined therapy in terms of the overall response rate (ORR) including complete remission (CR), CR with partial hematological recovery (CRh), CR with incomplete count recovery (CRi), morphologic leukemia free state (MLFS), and partial remission (PR). (Phase I expansion)

SECONDARY OBJECTIVES:

I. 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, cytogenetic response, and the 1-year overall survival (OS) in AML patients and the CR/marrow CR/hematologic improvement (HI) rate, partial remission (PR) rate and 1-year overall survival (OS) and cytogenetic response in MDS patients undergoing MDS/AML therapy combined with DMSA and Ca-EDTA.

II.To assess overall survival and event free survival in AML and MDS patients undergoing AML and MDS therapy combined with DMSA and Ca-EDTA III. To assess remission duration in AML and MDS patients undergoing AML and MDS therapy combined with DMSA and Ca-EDTA.

IV. To monitor toxic and essential metal levels during AML and MDS therapy combined with DMSA and Ca-EDTA and to evaluate the reduction in metals in the bone marrow and blood of newly diagnosed AML and MDS patients undergoing metal detoxification combined with standard AML/MDS therapy.

V. To evaluate the safety profile in AML and MDS patients undergoing AML and MDS therapy combined with DMSA and Ca-EDTA.

VI. Correlate metal and copper isotopic abundance ratios of AML and MDS 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 2017-0937 and PA15-0302.

VII. Estimate the progression rate in MDS patients. VIII. To assess other responses of interest. IX. To compare overall survival and response in this study with historical data of patients who were treated without Ca-EDTA and DMSA.

EXPLORATORY OBJECTIVES:

I. To correlate the degree of metal chelation with the degree of therapeutic response and minimal residual disease (MRD).

II. To collect environmental exposure data on the environmental health assessment survey.

III. To assess P53 folding before and after the first dose of Ca-EDTA chelation in MDS and AML patients.

IV. To study changes in cytogenetic/molecular data during treatment, as well as protein expression data (by immunohistochemistry and/or proteomics) including for transcription factors/tumor suppressors (e.g. TP53 and MYC).

V. To perform pre-clinical proof of concept studies of metals and metal chelators in a variety of AML cells and cell lines including: AML cell lines, primary hematologic malignancy cells, stromal cell lines, and patient-derived stromal cells.

OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 cohorts.

COHORT I: During standard of care chemotherapy, patients receive edetate calcium disodium intravenously (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.

COHORT II: During standard of care chemotherapy, patients receive succimer orally (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.

After completion of study treatment, patients are followed up every 3-12 months for up to 10 years. ;

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
• Blast Crisis
• Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
• Chronic Myelogenous Leukemia, BCR-ABL1 Positive
• High Risk Myelodysplastic Syndrome
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Neoplasm
• Myeloproliferative Disorders
• Myeloproliferative Neoplasm
• Neoplasm Metastasis
• Neoplasms
• Preleukemia
• Recurrence
• Recurrent Acute Myeloid Leukemia
• Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive
• Recurrent Myelodysplastic Syndrome
• Recurrent Myelodysplastic/Myeloproliferative Neoplasm
• Refractory Acute Myeloid Leukemia
• Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive
• Refractory Myelodysplastic Syndrome
• Secondary Acute Myeloid Leukemia
• Secondary Myelodysplastic Syndrome
• Syndrome

• NCT number: NCT03630991
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Contact: Maro Ohanian
• Phone: 713-792-2631
• Email: mohanian@mdanderson.org
• Status: Recruiting
• Phase: Phase 1
• Start date: October 11, 2018
• Completion date: April 30, 2025