Arsenic Trioxide, Ascorbic Acid, Dexamethasone, and Thalidomide in Myelofibrosis/Myeloproliferative Disorder

NCT00274820 | Completed Phase 2 DMC

• 1 other identifier: CASE4Y04
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Sometimes when chemotherapy is given, it does not stop the growth of cancer cells. The cancer is said to be resistant to chemotherapy. Giving ascorbic acid may reduce drug resistance and allow the cancer cells to be killed. Thalidomide may stop the growth of cancer cells by blocking blood flow to the cancer. Giving arsenic trioxide together with ascorbic acid, dexamethasone, and thalidomide may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving arsenic trioxide together with ascorbic acid, dexamethasone, and thalidomide works in treating patients with chronic idiopathic myelofibrosis or myelodysplastic or myeloproliferative disorders.

Conditions

Chronic Myeloproliferative Disorders; Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases

Keywords

chronic idiopathic myelofibrosis; chronic myelomonocytic leukemia; atypical chronic myeloid leukemia; myelodysplastic/myeloproliferative disease, unclassifiable; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes

Outcome Measures

Primary Outcomes (1)

• Response rate at 6 months

  Patients with any improvement in disease status (hematologic improvement or partial remission for patients with higher risk disease) may continue on study until a major response or complete remission occurs. Study visits will occur weekly for the first four weeks, then every four weeks, for each cycle. Laboratory monitoring to assess hematological parameters will occur weekly for the first four weeks, then every four weeks, for each cycle.

  at 6months of therapy and followed for at least 4 weeks after

Secondary Outcomes (3)

• Bone marrow response at 6 months

  at 6 months

• Spleen size at 12 weeks

  at 12 weeks

• Quality of life

  every 12 weeks

Interventions

ascorbic acid DIETARY_SUPPLEMENT

The dose of ascorbic acid will be 1000 mg PO 2-3 hours prior to ATO infusion. The treatment will follow the same schedule as arsenic trioxide.

Also known as: vitamin C

arsenic trioxide DRUG

Treatment consists of a loading period of five 0.25 mg/kg ATO doses in the first week, followed by maintenance dosing with 0.25 mg/kg ATO twice weekly for 11 weeks. Loading is usually done Monday through Friday of the first treatment week. Maintenance should be started either 72 or 96 hours after the last loading dose. Thereafter, dosing is twice weekly, following an alternating pattern of 72 and 96 hours. For example, maintenance dosing may be done on Mondays and Thursdays, Tuesdays and Fridays, etc. The same pattern should be followed for the entire maintenance dosing period.

Also known as: Trisenox®, ATO

dexamethasone DRUG

Dexamethasone will be given at a dose of 4mg PO daily for five days every four weeks (i.e., days 1-5, 29-33, 57-61, 84-88, etc.).

thalidomide DRUG

The dose of thalidomide will be 50 mg PO daily starting day 1. The dose will be increased to 100mg PO daily after two weeks if tolerated and only if patients experience \< grade 1 thalidomide-attributed toxicity using CTC criteria.

Also known as: Thalomid®

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Chronic idiopathic myelofibrosis or myelodysplastic/myeloproliferative disorders (MDS/MPD), including the following subtypes: * Chronic idiopathic myelofibrosis (with extramedullary hematopoiesis) * Chronic myelomonocytic leukemia (CMML) * Atypical chronic myeloid leukemia * MDS/MPD disease, unclassifiable * MDS with ≥ 2+ fibrosis present in the bone marrow * Patients with MPD must be negative by fluorescent in situ hybridization (FISH) for the BCR/ABL fusion gene PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Life expectancy of at least 3 months * Platelet count \> 10,000/mm³ * Bilirubin ≤ 2.5 times upper limit of normal (ULN) * SGOT and SGPT ≤ 2.5 times ULN * Creatinine ≤ 1.5 times ULN * Potassium ≥ 4.0 mEq/dL (supplemental electrolytes allowed) * Magnesium \> 1.8 mg/dL (supplemental electrolytes allowed) * Absolute QTc interval \< 460 msec * Patients who have a QT \> 460 after electrolyte repletion and discontinuation of other unessential QT-prolonging drugs will be excluded * Negative pregnancy test * Women of childbearing potential must use medically acceptable birth control (two methods of birth control or at least one highly active method and one additional effective method), starting 4 weeks prior to starting thalidomide, all through thalidomide therapy, and for 4 weeks after discontinuing thalidomide * Male patients with reproductive potential must use a latex condom every time they have sex with a woman from the time that they start taking thalidomide, all through thalidomide therapy, and for 4 weeks after discontinuing thalidomide * No sperm or blood donation during study treatment * Must be willing and able to comply with the FDA-mandated System for Thalidomide Educational Prescribing and Safety (S.T.E.P.S™) program * No other serious medical condition, laboratory abnormality, or psychiatric illness that, in the view of the treating physician, would place the patient at an unacceptable risk if he or she were to participate in the study or would prevent that person from giving informed consent * No preexisting neurotoxicity/neuropathy ≥ grade 2 * Not pregnant or nursing * No cardiac conduction defects * No unstable angina * No myocardial infarction within the past 6 months * No congestive heart failure of any cause * No New York Heart Association class II or greater * No other significant underlying cardiac dysfunction * No prior malignancy in the 3 years before treatment in this study (other than curatively treated carcinoma in situ of the cervix or nonmelanoma skin cancer) * No sulfa allergy that would interfere with administration of trimethoprim sulfamethoxazole prophylaxis * Patients with sulfa allergies who could instead receive pentamidine prophylaxis also will be excluded * Patients with sulfa allergies who can instead receive atovaquone may be included PRIOR CONCURRENT THERAPY: * At least 4 weeks since prior investigational or approved therapy for this disease * No growth factors within 1 week of study enrollment * No other concurrent cytotoxic drugs or other investigational agents

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (2)

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Myeloproliferative Disorders; Leukemia; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Primary Myelofibrosis; Leukemia, Myelomonocytic, Chronic; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative

Interventions

Ascorbic Acid; Arsenic Trioxide; Dexamethasone; Thalidomide

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Neoplasms; Leukemia, Myeloid; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Mikkael A. Sekeres, MD, MS

  The Cleveland Clinic

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2006
• First Posted: January 11, 2006
• Study Start: October 1, 2005
• Primary Completion: September 1, 2007
• Study Completion: October 1, 2007
• Last Updated: July 27, 2020

Record last verified: 2020-07

Locations

US (2)