Vorinostat and Idarubicin in Treating Patients With Relapsed or Refractory Leukemia or Myelodysplastic Syndromes

NCT00331513 | Completed Phase 1

• 5 other identifiers: NCI-2009-00094CDR00004720622005-00316892U01CA062461
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized phase I trial is studying the side effects and best dose of vorinostat when given together with idarubicin in treating patients with relapsed or refractory leukemia or myelodysplastic syndromes. Drugs used in chemotherapy, such as vorinostat and idarubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving vorinostat together with idarubicin may kill more cancer cells.

Conditions

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; 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); Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (1)

• Maximum-tolerated dose (MTD) of vorinostat determined by dose-limiting toxicities (DLT) as measured by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.3.0

  21 days

Study Arms (2)

Arm I (vorinostat, idarubicin)

ACTIVE COMPARATOR

Patients receive oral SAHA three times daily on days 1-14 and idarubicin IV over 15 minutes once daily on days 1-3. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients completing 6 courses of therapy or who reach the maximum cumulative dose of idarubicin or an equivalent anthracycline and achieve clinical benefit may continue treatment with SAHA alone 3 times daily on days 1-14 of each course, in the absence of disease progression or unacceptable toxicity.

Drug: vorinostat; Drug: idarubicin; Other: laboratory biomarker analysis; Other: pharmacological study

Arm II (vorinostat, idarubicin)

ACTIVE COMPARATOR

Patients receive oral SAHA three times daily and idarubicin IV over 15 minutes once daily on days 1-3. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients completing 6 courses of therapy or who reach the maximum cumulative dose of idarubicin or an equivalent anthracycline and achieve clinical benefit may continue treatment with SAHA alone 3 times daily on days 1-14 of each course, in the absence of disease progression or unacceptable toxicity.

Drug: vorinostat; Drug: idarubicin; Other: laboratory biomarker analysis; Other: pharmacological study

Interventions

vorinostat DRUG

Given orally

Also known as: L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza

Arm I (vorinostat, idarubicin); Arm II (vorinostat, idarubicin)

idarubicin DRUG

Given IV

Also known as: 4-demethoxydaunorubicin, 4-DMDR, DMDR, IDA

Arm I (vorinostat, idarubicin); Arm II (vorinostat, idarubicin)

laboratory biomarker analysis OTHER

Correlative studies

Arm I (vorinostat, idarubicin); Arm II (vorinostat, idarubicin)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm I (vorinostat, idarubicin); Arm II (vorinostat, idarubicin)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed relapsed/refractory acute myelogenous leukemia, acute lymphocytic leukemia, myelodysplastic syndrome or blastic phase chronic myelogenous leukemia.
• Patients that have received cumulative doses (or its equivalent to other anthracycline) of more than 290 mg/m\^2 of idarubicin will be excluded from the study. No other limitations in terms of number of prior therapies or type of therapies apply to this study.
• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
• Total bilirubin ≤ 2 mg/dL
• AST and ALT ≤ 2.5 times upper limit of normal
• Creatinine ≤ 2 mg/dL
• LVEF ≥ 50%
• Not nursing or pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception
• At least 2 weeks since prior chemotherapy and recovered, unless there is evidence of rapidly progressive disease, at least 24 hours since prior hydroxyurea for rapidly proliferating disease
• At least 2 weeks since prior imatinib mesylate
• At least 2 weeks since prior histone deacetylase inhibitors, including valproic acid
• Maximum cumulative dose of prior idarubicin or equivalent anthracycline drug ≤ 290 mg/m2
• No concurrent epoetin alfa or hematopoietic colony-stimulating factors during the first course of study therapy

You may not qualify if:

• Patients with clinical evidence of CNS disease should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• No unstable angina pectoris
• Considered ineligible for or refused potentially curative therapy, including allogeneic stem cell transplantation, with or without standard induction therapy
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to vorinostat (SAHA) or other agents used in this study
• No ongoing or active infection
• No symptomatic congestive heart failure
• No cardiac arrhythmia
• No other uncontrolled illness
• No psychiatric illness or social situation that would preclude study compliance
• No other concurrent investigational agents
• No other concurrent anticancer agents or therapies
• No concurrent combination antiretroviral therapy for HIV-positive patients

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Congenital Abnormalities; Leukemia, Promyelocytic, Acute; Blast Crisis; Myeloproliferative Disorders; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute

Interventions

Vorinostat; Idarubicin

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Guillermo Garcia-Manero

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 30, 2006
• First Posted: May 31, 2006
• Study Start: March 1, 2006
• Primary Completion: January 1, 2010
• Last Updated: September 30, 2013

Record last verified: 2013-09

Locations

US (1)