Panobinostat in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia

NCT ID: NCT00723203

Last Updated: 2014-09-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2010-09-30

Brief Summary

RATIONALE: Panobinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying the side effects of panobinostat and to see how well it works in treating patients with relapsed or refractory acute lymphoblastic leukemia or acute myeloid leukemia.

Detailed Description

OBJECTIVES:

Primary

• To determine the antitumor activity of panobinostat, in terms of objective response rate, time to progression, and survival, in patients with relapsed or refractory acute lymphoblastic leukemia or acute myeloid leukemia.
• To assess the toxicity of panobinostat in these patients.

Secondary

• To perform correlative laboratory studies to assess changes in various proteins that may be altered by histone deacetylase inhibition therapy.

OUTLINE: Patients receive oral panobinostat once on days 1, 3, and 5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo peripheral blood and bone marrow sample collection at baseline and on day 28 of course 1 for correlative laboratory studies. Samples are analyzed by RT-PCR for reactivation of FANCG, FOXO3A, GADD45A, GADD45B, GADD45G, H2AX, and TP73.

After completion of study treatment, patients are followed for at least 4 weeks.

PROJECTED ACCRUAL: A total of 74 patients (37 with acute myeloid leukemia and 37 with acute lymphoblastic leukemia) will be accrued for this study.

Conditions

Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (panobinostat)

Patients receive oral panobinostat once on days 1, 3, and 5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

panobinostat: 40 mg Monday, Wednesday and Friday of every week in a 28 day cycle

Group Type: EXPERIMENTAL

panobinostat

Intervention Type: DRUG

40 mg Monday, Wednesday and Friday of every week in a 28 day cycle

gene expression analysis

Intervention Type: GENETIC

Day 1 and day 28 samples

reverse transcriptase-polymerase chain reaction

Intervention Type: GENETIC

Day 1 and day 28 samples

laboratory biomarker analysis

Intervention Type: OTHER

Day 1 and day 28 samples

Interventions

panobinostat

40 mg Monday, Wednesday and Friday of every week in a 28 day cycle

Intervention Type: DRUG

gene expression analysis

Day 1 and day 28 samples

Intervention Type: GENETIC

reverse transcriptase-polymerase chain reaction

Day 1 and day 28 samples

Intervention Type: GENETIC

laboratory biomarker analysis

Day 1 and day 28 samples

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Patients who have relapsed after prior autologous or allogenic stem cell transplant are eligible
• No active CNS disease

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Serum albumin ≥ 3 g/dL
• AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5.0 times ULN if transaminase elevation is due to leukemic involvement)
• Bilirubin ≤ 1.5 times ULN
• Creatinine ≤ 1.5 times ULN or creatinine clearance ≥ 50 mL/min
• Potassium ≥ lower limit of normal (LLN)
• Phosphorous ≥ LLN
• Serum total calcium (corrected for serum albumin) or serum ionized calcium ≥ LLN
• Magnesium ≥ LLN
• Thyroid stimulating hormone and free T4 normal (thyroid hormone replacement therapy allowed)
• LVEF ≥ LLN by MUGA or ECHO
• No impaired cardiac function, including any of the following:

• QTc > 450 msec
• Congenital long QT syndrome
• History of sustained ventricular tachycardia
• History of ventricular fibrillation or torsades de pointes
• Bradycardia (i.e., heart rate < 50 beats per minute)

• Pacemaker allowed provided heart rate ≥ 50 beats per minute
• Myocardial infarction or unstable angina within the past 6 months
• New York Heart Association class III-IV congestive heart failure
• Right bundle branch block and left anterior hemiblock (bifascicular block)
• No uncontrolled hypertension
• No unresolved diarrhea > CTCAE grade 1
• No impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral panobinostat
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-barrier contraception during and for 3 months after completion of study treatment
• No other primary malignancy within the past 5 years, other than curatively treated carcinoma in situ of the cervix or basal cell or squamous cell carcinoma of the skin
• No HIV or hepatitis C positivity
• No other concurrent severe and/or uncontrolled medical condition
• No significant history of non-compliance to medical regimens or inability to give reliable informed consent

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from all prior therapy
• More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy
• More than 4 weeks since prior valproic acid
• No other prior treatment with a histone deacetylase inhibitor
• No concurrent medication that may cause QTc prolongation or induce torsades de pointes
• No concurrent CYP3A4 inhibitors
• No concurrent grapefruit, grapefruit juice, or Seville (sour) oranges
• No concurrent radiotherapy
• No other concurrent anticancer therapy or investigational therapy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Leslie Popplewell, MD

Role: PRINCIPAL_INVESTIGATOR

City of Hope Comprehensive Cancer Center

Locations

City of Hope Comprehensive Cancer Center

Duarte, California, United States

South Pasadena Cancer Center

Pasadena, California, United States

Countries

United States

Other Identifiers

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CHNMC-07174

Identifier Type: -

Identifier Source: secondary_id

NOVARTIS-CHNMC-07174

Identifier Type: -

Identifier Source: secondary_id

CDR0000601203

Identifier Type: REGISTRY

Identifier Source: secondary_id

07174

Identifier Type: -

Identifier Source: org_study_id