LBH589 in Relapsed or Relapsed and Refractory Waldenstrom's Macroglobulinemia

NCT00936611 | Completed Phase 2 Results DMC

• 2 other identifiers: 09-071CLBH589CUS56T
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this research study is to assess the overall response rate of LBH589 in patients with relapsed or refractory Waldenstrom's Macroglobulinemia. LBH589 is a newly discovered compound that has killed Waldenstrom cells in laboratory studies, however, it is not known if LBH589 will show the same activity in people with Waldenstrom's Macroglobulinemia. This drug has been used in research for the treatment of other types of cancer, such as multiple myeloma.

Conditions

Waldenstrom's Macroglobulinemia

Keywords

LBH589; WM; panobinostat; relapsed; waldenstrom; macroglobulinemia

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Overall response rate is percentage of participants with complete (CR), very good partial (VGPR), partial (PR), or minimal response (MR) as best response during treatment. CR * Disappearance of monoclonal protein by immunofixation * No histologic evidence of bone marrow involvement * Resolution of any adenopathy/organomegaly (confirmed by CT scan), or signs or symptoms attributable to WM. * Second immunofixation required for confirmation. VGPR -At least 90% reduction of serum monoclonal IgM concentration on protein electrophoresis. PR * At least 50% reduction of serum monoclonal IgM concentration on protein electrophoresis and at least 50% decrease in adenopathy/organomegaly on physical examination or on CT scan. * No new symptoms or signs of active disease. MR * At least 25% but less than 50% reduction of serum monoclonal IgM by protein electrophoresis. * No new symptoms or signs of active disease.

  Assessed after 2nd cycle and then every subsequent cycle for 6 cycles. The median number of completed cycles of therapy was 5 (0- 32). As such observed up to ~32 months.

Secondary Outcomes (5)

• Median Progression Free Survival

  Assessed after 2nd cycle and then every subsequent cycle for 6 cycles and then every 3 months. If taken off treatment at cycle 2 for disease progression, assessed every 3 months. The median (range) follow up from treatment start is 7.7 month (0.9 - 29.7).

• Median Time to Progression

  Assessed after 2nd cycle and then every subsequent cycle for 6 cycles and then every 3 months. If taken off treatment at cycle 2 for disease progression, assessed every 3 months. The median (range) follow up from treatment start is 7.7 month (0.9 - 29.7).

• Median Duration of Response

  Assessed after 2nd cycle and then every subsequent cycle for 6 cycles and then every 3 months. If taken off treatment at cycle 2 for disease progression, assessed every 3 months. The median (range) follow up from treatment start is 7.7 month (0.9 - 29.7).

• Number of Participants With Grade 3 and 4 Treatment-Related Thrombocytopenia

  Assessed after 2nd cycle, every subsequent cycle for 6 cycles and then every 3 months. Once off-treatment, adverse events will be assessed for 30 days. The median (range) number of completed cycles of therapy was 5 (0- 32). Therefore, up to ~33 months.

• Acetylated Histone H3 and Overall Response Association

  Bone marrow biopsies were obtained at the start of treatment (baseline) and after the 6th cycle.

Study Arms (1)

LBH589

EXPERIMENTAL

30 mg three days a week (Mondays, Wednesdays and Fridays). 1 cycle was 28 days Dose modifications for attributable toxicities allowed for reduction to: * 25 mg, 20 mg three times a week every week * Or 20 mg three times a week every other week. No dose re-escalation was allowed. * The protocol was amended on 6/15/2010 because of concerns of toxicity to allow a starting dose of 25 mg; 12/36 (33%) patients were enrolled on the 25 mg dose.

Drug: LBH589

Interventions

LBH589 DRUG

Also known as: panobinostat

LBH589

Eligibility Criteria

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

You may qualify if:

• Male or female patients aged 18 years or older
• Must have received prior therapy for their WM, any number of prior therapies is allowed
• Must have symptomatic relapsed or refractory WM
• Measurable monoclonal IgM protein in the blood and presence of lymphoplasmacytic cells in the bone marrow during any previous bone marrow
• Laboratory values as described in the protocol
• Clinically euthyroid
• ECOG Performance Status of 2 or less

You may not qualify if:

• Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
• Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first LBH589 treatment
• Peripheral neuropathy CTCAE grade 2 or higher
• Impaired cardiac function or clinically significant cardiac diseases
• Impairment of GI function or GI disease that may significantly alter the absorption of LBH589
• Diarrhea \> CTCAE grade 1
• Other concurrent severe and/or uncontrolled medical conditions including abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol
• Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug
• Patients who have received targeted agents within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is longer) and who have not recovered from side effects of those therapies
• Patients who have received chemotherapy or rituximab within 3 weeks or less; or radiation therapy to \> 30% of marrow-bearing bone within 2 weeks or less prior to starting study treatment; or who have not yet recovered from side effects of such therapies
• Patients who have received corticosteroids 2 weeks or less prior to registration. Patients may be receiving chronic corticosteroids if they are being given for disorders other than than Waldenstrom's Macroglobulinemia
• Patients with active bleeding tendency or receiving any treatment with therapeutic doses of sodium warfarin or coumadin derivatives. Low doses of Coumadin to maintain line patency is allowed
• Patients who have undergone major surgery 4 weeks or less prior to starting study drug or who have not recovered from side effects of such therapy
• Women who are pregnant or breast feeding or women of childbearing potential not using an effective method of birth control
• Male patients whose sexual partners are women of childbearing potential not using effective methods of birth control

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Brigham and Women's Hospital: collaborator
• Novartis: collaborator

Study Sites (2)

Rocky Mountain Cancer Centers

Denver, Colorado, 80220, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Ghobrial IM, Campigotto F, Murphy TJ, Boswell EN, Banwait R, Azab F, Chuma S, Kunsman J, Donovan A, Masood F, Warren D, Rodig S, Anderson KC, Richardson PG, Weller E, Matous J. Results of a phase 2 trial of the single-agent histone deacetylase inhibitor panobinostat in patients with relapsed/refractory Waldenstrom macroglobulinemia. Blood. 2013 Feb 21;121(8):1296-303. doi: 10.1182/blood-2012-06-439307. Epub 2013 Jan 3.

  PMID: 23287861 RESULT

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia; Recurrence

Interventions

Panobinostat

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Irene Ghobrial
• Organization: Dana-Farber Cancer Institute

irene_ghobrial@dfci.harvard.edu

6176324101

Study Officials

• Irene Ghobrial, MD

  Dana-Farber Cancer Institute

  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: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 9, 2009
• First Posted: July 10, 2009
• Study Start: July 1, 2009
• Primary Completion: September 1, 2011
• Study Completion: November 1, 2012
• Last Updated: January 28, 2021
• Results First Posted: January 28, 2021

Record last verified: 2021-01

Locations

US (2)