A Leukemia SPORE Phase II Clinical Trial Comparing Decitabine Versus Decitabine/Carboplatin and Decitabine/Arsenic for the Treatment of Relapsed, Refractory, and Elderly Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)

Leukemia Clinical Trial

Official title:

Leukemia SPORE Phase II Randomized Study of Decitabine Versus Decitabine and Carboplatin Versus Decitabine and Arsenic in Relapsed, Refractory and Elderly Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02188706
• Other study ID #: 2013-0543
• Secondary ID: CA100632NCI-2014
• Status: Active, not recruiting
• Phase: Phase 2
• First received: July 10, 2014
• Last updated: April 11, 2018
• Start date: July 2014
• Est. completion date: July 2026

Study information

• Verified date: April 2018
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical research study is to compare the response rates of patients receiving decitabine alone, decitabine with carboplatin, and decitabine with arsenic trioxide in patients with AML or MDS.

Description:

Study Groups:

If you are found to be eligible to take part in this study and you are one of the first 30 participants enrolled, you will have an equal chance of being in one of 3 study groups. If you enroll after the first 30 participants are enrolled, you will have a higher chance of being assigned to the group is having better results.

• If you are in Group 1, you will receive decitabine alone.

• If you are in Group 2, you will receive decitabine and carboplatin.

• If you are in Group 3, you will receive decitabine and arsenic trioxide.

Study Drug Administration:

Every 4 weeks is a study cycle.

You will receive decitabine by vein over about 1 hours on Days 1-5 of each cycle.

If you are receiving carboplatin, you will receive it over 1 hour on Day 8 (+/-2 days) of each cycle.

If you are receiving arsenic trioxide, you will receive it over about 1 hour on Days 1-5 of each cycle

Study Visits:

Blood (about 1-2 teaspoons) will be drawn 1-2 times a week during Cycle 1 and then every 2-4 weeks after that for routine tests. If you have stable disease, blood will only be drawn every 4-6 weeks.

On Day 28 of Cycle 3 (+/- 3 days), you will have a bone marrow aspirate and biopsy to check the status of the disease. After that, you will have bone marrow biopsies/aspirations when the doctor thinks it is needed.

If you are in Group 3, you will have EKGs on Day 1 of each cycle before receiving the study drugs. On Days 1 and 4 of each cycle, blood (about 1-2 teaspoons) will also be drawn for routine tests before your dose of the study drugs.

If you are taken off study, blood (about 1-2 teaspoons) will be drawn for routine tests.

Length of Study:

You may continue taking the study drugs for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug(s) if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

This is an investigational study. Arsenic trioxide is FDA approved and commercially available for the treatment of APL. Decitabine is FDA approved and commercially available for the treatment of MDS. Carboplatin is FDA approved and commercially available for the treatment solid tumors. The study drug or study drug combination you receive on this study are considered investigational.

Up to 120 patients will take part in this study. Up to 20 patients will be enrolled at MD Anderson.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: July 2026
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients with AML, relapsed or refractory to standard therapy or elderly patients with AML (age 65 or over). Patients who have AML and are younger than age 65 but considered unfit for conventional chemotherapy are eligible. Patients with de novo or treated MDS or CMML INT-1 or above are eligible. Patients may have had prior exposure to azacitidine but no more than one cycle of decitabine. Patients must have been off chemotherapy for 2 weeks prior to entering this study and have recovered from the toxicities of that therapy; A caveat to this is in the case of rapidly progressive disease. Hydroxyurea is permitted for control of elevated WBC prior to treatment and can be continued for the first 4 weeks of therapy. Erythropoiesis stimulating agents (ESAs) and GCSF are allowed before therapy. ESAs, GCSF or other growth factors are permitted on therapy.

2. Performance 0-2 (ECOG).

3. Adequate cardiac functions assessed by 2D ECHO (NYHA cardiac III-IV excluded).

4. Pre-treatment EKG

5. Adequate end organ function with creatinine </= 2mg/dL and total bilirubin </= 2mg/dL, AST and ALT </= or = 2.5 X institutional ULN.

6. Absence of significant intercurrent illness such as uncontrolled heart failure, unstable angina, cardiac arrhythmia and psychiatric illness which precludes the giving of informed consent.

7. Signed informed consent

Exclusion Criteria:

1. Nursing and pregnant females. Patients of childbearing potential should practice effective methods of contraception. Should a woman become preg-nant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

2. Current uncontrolled infections.

3. Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.

4. Chronic kidney disease > stage 3.

5. HIV infection.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• Decitabine
20 mg/m2 by vein daily over 1 hour on Days 1-5 of each 28 day cycle.
• Carboplatin
AUC 5 by vein over 1 hour on Day 8 of each 28 day cycle.
• Arsenic Trioxide
0.15 mg/kg by vein over 1 hour on Days 1-5 of each 28 day cycle.

Locations

Country	Name	City	State
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Temple University Bone Marrow Transplant Program	Philadelphia	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	Leukemia SPORE, TEVA

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response	Overall response defined as complete response (CR), partial response (PR) or immunologic improvement (IH). CR defined as normalization of peripheral blood and bone marrow with < 5% bone marrow blasts, a peripheral blood granulocyte count > (1.0 x 109/ L, and a platelet count > 100 x 109/L). Partial Remission: as above except for presence of 6-15% marrow blasts, or 50% reduction if <15% at start of treatment. Clinical benefit: Hematologic improvements as defined in modified IWG criteria in MDS (Cheson BD, et al., Blood 2006, 108(2):419) also measured.	28 days

External Links

•   University of Texas MD Anderson Cancer Center Website