Decitabine and Bortezomib in Treating Patients With Acute Myeloid Leukemia

NCT00703300 | Completed Phase 1

• 8 other identifiers: NCI-2009-00263OSU-080472008C0034CDR0000598089080478008U01CA076576P30CA016058
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial is studying the side effects and best dose of bortezomib when given together with decitabine in treating patients with acute myeloid leukemia. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with decitabine may kill more cancer cells.

Conditions

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (3)

• Maximum-tolerated dose (MTD) of bortezomib in combination with decitabine

  If a patient meets the definition of dose-limiting toxicity (DLT), the patient may continue on with study therapy provided that the toxicity can be managed according to the dose modification guidelines. For DLT = 2, dose level will stop. This dose level will be declared the MTD administered dose (highest dose administered). As an exploratory, phase I study, no inferential statistical tests of hypotheses are planned. Data collected will be descriptive and provide limited estimates of variability given the small sample sizes at each dose level.

  During course 1 (28 days)

• Specific toxicities

  Toxicity will be characterized using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. As an exploratory, phase I study, no inferential statistical tests of hypotheses are planned. Data collected will be descriptive and provide limited estimates of variability given the small sample sizes at each dose level.

  Up to 30 days post-treatment

• DLT of bortezomib in combination with decitabine

  Toxicity will be characterized using the National Cancer Institute CTCAE version 3.0. As an exploratory, phase I study, no inferential statistical tests of hypotheses are planned. Data collected will be descriptive and provide limited estimates of variability given the small sample sizes at each dose level.

  During course 1 (28 days)

Secondary Outcomes (2)

• Overall response rate

  Up to 30 days post-treatment

• Rate of complete remission (CR)

  Up to 30 days post-treatment

Study Arms (1)

Treatment (enzyme inhibitor therapy and chemotherapy)

EXPERIMENTAL

Patients receive decitabine IV over 1 hour on days 1-5 or 1-10 and bortezomib IV on days 5 and 8 or days 5, 8, 12, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Once the maximum tolerated dose is determined, an additional 6 patients are treated at the recommended phase II dose.

Drug: bortezomib; Drug: decitabine; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

bortezomib DRUG

Given IV

Also known as: LDP 341, MLN341, VELCADE

Treatment (enzyme inhibitor therapy and chemotherapy)

decitabine DRUG

Given IV

Also known as: 5-aza-dCyd, 5AZA, DAC

Treatment (enzyme inhibitor therapy and chemotherapy)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (enzyme inhibitor therapy and chemotherapy)

laboratory biomarker analysis OTHER

Optional correlative studies

Treatment (enzyme inhibitor therapy and chemotherapy)

Eligibility Criteria

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

You may qualify if:

• Diagnosis of acute myeloid leukemia (AML), meeting one of the following criteria:
• Relapsed or refractory disease (≥ 18 years of age)
• Previously untreated disease (≥ 60 years of age)
• Secondary AML or therapy-related AML allowed
• No granulocytic sarcoma as the sole site of disease
• No active or relapsed CNS disease
• No advanced malignant solid tumors
• ECOG performance status 0-2
• Life expectancy \> 6 months (if patient has co-morbid illness)
• Total bilirubin \< 2.0 mg/dL
• AST and ALT \< 2.5 times upper limit of normal
• Creatinine \< 2.0 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• Blum W, Schwind S, Tarighat SS, Geyer S, Eisfeld AK, Whitman S, Walker A, Klisovic R, Byrd JC, Santhanam R, Wang H, Curfman JP, Devine SM, Jacob S, Garr C, Kefauver C, Perrotti D, Chan KK, Bloomfield CD, Caligiuri MA, Grever MR, Garzon R, Marcucci G. Clinical and pharmacodynamic activity of bortezomib and decitabine in acute myeloid leukemia. Blood. 2012 Jun 21;119(25):6025-31. doi: 10.1182/blood-2012-03-413898. Epub 2012 May 7.

  PMID: 22566605 DERIVED

MeSH Terms

Conditions

Congenital Abnormalities; Leukemia, Myeloid, Acute

Interventions

Bortezomib; Decitabine

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azacitidine; Aza Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• William Blum

  Ohio State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2008
• First Posted: June 23, 2008
• Study Start: June 1, 2008
• Primary Completion: March 1, 2010
• Study Completion: October 1, 2014
• Last Updated: November 7, 2014

Record last verified: 2014-09

Locations

US (1)