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

NCT00723203 | Terminated Phase 2 Results DMC

• 5 other identifiers: 07174P30CA033572CHNMC-07174NOVARTIS-CHNMC-07174CDR0000601203
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

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.

Conditions

Leukemia

Keywords

Philadelphia chromosome positive adult precursor acute lymphoblastic leukemia; recurrent adult acute lymphoblastic leukemia; recurrent adult acute myeloid leukemia

Outcome Measures

Primary Outcomes (1)

• Hematological Response Rate

  Morphologic CR: morphologic leukemia-free state with absolute neutrophil count \> 1000/uL and platelet count ≥ 100,000/uL and independent of blood transfusions. Cytogenic CR: morphologic CR along with reversion to a normal karyotype by cytogenetic analysis. Molecular CR: morphologic CR with no residual disease by molecular or flow cytometric detection methods. Morphologic CR with incomplete blood recovery (CRi): morphologic CR except for residual neutropenia (\<1000/uL) and/or thrombocytopenia (\<1000,000/uL). PR: same hematologic values for a CR but with a decrease of at least 50% in percentage of blasts to a post-treatment value of 5% to 25% in bone marrow aspirate. (If the pre-treatment blast percentage was 50-100% this must decrease to a value between 5-25%. If the pre-treatment blast percentage was 20-49% this must decrease by at least half to a value \> 5%.) A value ≤ 5% is also considered a PR if Auer rods are present. Hematological response = morphologic CR+PR.

  Up to 6 cycles of treatment, up to 24 weeks.

Study Arms (1)

Treatment (panobinostat)

EXPERIMENTAL

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

Drug: panobinostat; Genetic: gene expression analysis; Genetic: reverse transcriptase-polymerase chain reaction; Other: laboratory biomarker analysis

Interventions

panobinostat DRUG

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

Treatment (panobinostat)

gene expression analysis GENETIC

Day 1 and day 28 samples

Treatment (panobinostat)

reverse transcriptase-polymerase chain reaction GENETIC

Day 1 and day 28 samples

Treatment (panobinostat)

laboratory biomarker analysis OTHER

Day 1 and day 28 samples

Treatment (panobinostat)

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed acute myeloid leukemia or acute lymphoblastic leukemia (ALL) * Relapsed or refractory disease * Patients with Philadelphia chromosome-positive (Ph+) ALL refractory to BCR/ABL inhibitors are eligible * 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

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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010-3000, United States

Location

South Pasadena Cancer Center

Pasadena, California, 91030, United States

Location

MeSH Terms

Conditions

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute

Interventions

Panobinostat; Gene Expression Profiling; Reverse Transcriptase Polymerase Chain Reaction

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Genetic Techniques; Investigative Techniques; Polymerase Chain Reaction; Nucleic Acid Amplification Techniques

Limitations and Caveats

There were no responses observed in the first 12 evaluable patients accrued to the first stage of the two-stage Optimum design of Simon. As a result the study was terminated due to a lack of efficacy.

Results Point of Contact

• Title: Paul Frankel, Ph.D.
• Organization: City of Hope National Medical Center

pfrankel@coh.org

(626)359-8111

Study Officials

• Leslie Popplewell, MD

  City of Hope Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: July 25, 2008
• First Posted: July 28, 2008
• Study Start: April 1, 2008
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2010
• Last Updated: September 9, 2014
• Results First Posted: August 28, 2014

Record last verified: 2014-09

Locations

US (2)