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

Primary Purpose

Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Edetate Calcium Disodium
Multivitamin
Succimer
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Understand and voluntarily sign an informed consent form
  • Diagnosis of any of the following:

    • 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 myeloproliferative neoplasm (MPN) (including myeloid blast phase of chronic myeloid leukemia [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
  • Patients on non-investigational regimens or on investigational new drug (IND)-exempt MD Anderson studies (for hematologic malignancies) of approved drugs are also eligible
  • Patients on IND studies (for hematologic malignancies) utilizing Food and Drug Administration (FDA) approved commercially available drugs are eligible
  • Investigational agents that are not used for treatment of the leukemia per se (e.g. anti-infective prophylaxis or therapy) will be allowed. Other supportive care studies are allowed, even if under an IND
  • Newly diagnosed MDS or AML, as well as MDS/MPN, myeloid blast phase of MPN (including myeloid blast phase of CML), patients can enroll on this study after start of non-investigational induction therapy, but must be within first 3 cycles of therapy and benefiting from their front-line therapy. Patients with 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 are eligible for these salvage cohorts if they are within the first 3 cycles of salvage 1 or salvage 2 therapy
  • 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
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 at study entry
  • Serum creatinine =< 1.5 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]) and/or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.0 x ULN (unless due to leukemia or other hematologic malignancy)
  • 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
  • Extramedullary disease is allowed as long as it can be measured and followed for response

Exclusion Criteria:

  • 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
  • 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)

Sites / Locations

  • M D Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cohort I (edetate calcium disodium, multivitamin)

Cohort II (succimer, multivitamin)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Incidence of adverse events
Safety data of the patients will be summarized using descriptive statistics such as mean, standard deviation, median and range. Will follow standard reporting guidelines for adverse events. Safety data will be summarized by category, severity and frequency.
Maximum tolerated doses (MTD) of edetate calcium disodium (Ca-EDTA) and succimer (DMSA) (Phase 1 dose escalation)
The MTD is the highest dose level in which < 2 patients of 6 develop first cycle dose-limiting toxicity (DLT).

Secondary Outcome Measures

Full Information

First Posted
August 10, 2018
Last Updated
September 18, 2023
Sponsor
M.D. Anderson Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT03630991
Brief Title
Edetate Calcium Disodium or Succimer in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome Undergoing Chemotherapy
Official Title
Monitoring, Detoxifying, and Rebalancing Metals During Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 11, 2018 (Actual)
Primary Completion Date
April 30, 2025 (Anticipated)
Study Completion Date
April 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Chronic Myelogenous Leukemia, BCR-ABL1 Positive, High Risk Myelodysplastic Syndrome, Myelodysplastic Syndrome, Myelodysplastic/Myeloproliferative Neoplasm, Myeloproliferative Neoplasm, 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, Very High Risk Myelodysplastic Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
58 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort I (edetate calcium disodium, multivitamin)
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort II (succimer, multivitamin)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Edetate Calcium Disodium
Other Intervention Name(s)
C10H12CaN2Na2O8, Calcium disodium edetate, Calcium Disodium Ethylenediaminetetraacetate, Calcium Disodium Versenate, Calcium EDTA, Disodium calcium ethylenediaminetetraacetate, EDTA Calcium
Intervention Description
Given IV
Intervention Type
Dietary Supplement
Intervention Name(s)
Multivitamin
Other Intervention Name(s)
Geritol, Vitamin Supplements (NOS)
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Succimer
Other Intervention Name(s)
Chemet, DMSA, Meso 2, 3-Dimercaptosuccinic Acid
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Incidence of adverse events
Description
Safety data of the patients will be summarized using descriptive statistics such as mean, standard deviation, median and range. Will follow standard reporting guidelines for adverse events. Safety data will be summarized by category, severity and frequency.
Time Frame
At 30 days post-treatment
Title
Maximum tolerated doses (MTD) of edetate calcium disodium (Ca-EDTA) and succimer (DMSA) (Phase 1 dose escalation)
Description
The MTD is the highest dose level in which < 2 patients of 6 develop first cycle dose-limiting toxicity (DLT).
Time Frame
Up to the end of cycle 1 (each cycle is 28 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Understand and voluntarily sign an informed consent form Diagnosis of any of the following: 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 myeloproliferative neoplasm (MPN) (including myeloid blast phase of chronic myeloid leukemia [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 Patients on non-investigational regimens or on investigational new drug (IND)-exempt MD Anderson studies (for hematologic malignancies) of approved drugs are also eligible Patients on IND studies (for hematologic malignancies) utilizing Food and Drug Administration (FDA) approved commercially available drugs are eligible Investigational agents that are not used for treatment of the leukemia per se (e.g. anti-infective prophylaxis or therapy) will be allowed. Other supportive care studies are allowed, even if under an IND Newly diagnosed MDS or AML, as well as MDS/MPN, myeloid blast phase of MPN (including myeloid blast phase of CML), patients can enroll on this study after start of non-investigational induction therapy, but must be within first 3 cycles of therapy and benefiting from their front-line therapy. Patients with 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 are eligible for these salvage cohorts if they are within the first 3 cycles of salvage 1 or salvage 2 therapy 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 Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 at study entry Serum creatinine =< 1.5 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]) and/or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.0 x ULN (unless due to leukemia or other hematologic malignancy) 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 Extramedullary disease is allowed as long as it can be measured and followed for response Exclusion Criteria: 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 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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Maro Ohanian
Phone
713-792-2631
Email
mohanian@mdanderson.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maro Ohanian
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maro Ohanian
Phone
713-792-2631
Email
mohanian@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Maro Ohanian

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center Website

Learn more about this trial

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

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