Ibrutinib in Treating Patients With Advanced Systemic Mastocytosis

NCT02415608 | Terminated Phase 2 Results DMC FDA Drug

• 4 other identifiers: IRB-31815NCI-2014-02341HEMMPD0021P30CA124435
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This phase 2 trial studies ibrutinib to see how well it works in treating patients with systemic (affecting the entire body) mastocytosis that has spread to other parts of the body and usually cannot be cured or controlled with treatment (advanced). Systemic mastocytosis is a disease in which too many mast cells (a type of immune system cell) are found throughout the body. Mast cells give off chemicals such as histamine that can cause flushing (a hot, red face), itching, abdominal cramps, muscle pain, nausea, vomiting, diarrhea, low blood pressure, and shock. Ibrutinib may stop the growth of mast cells by blocking some of the enzymes needed for cell growth.

Conditions

Aggressive Systemic Mastocytosis; Mast Cell Leukemia; Systemic Mastocytosis

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Overall response rate (ORR) is reported as the sum of the rates of participants achieving complete remission (CR), partial remission (PR), \& clinical improvement (CI). A clinical response is a response with duration of ≥ 12 weeks. CR is defined as all 4 criteria: * No presence of compact neoplastic mast cell aggregates * Serum tryptase level \< 20 ng/mL * Peripheral blood count remission defined as absolute neutrophil count (ANC) ≥1 x 10e9/L + normal differential, Hb ≥11 g/dL, \& platelet count ≥100x10e9/L * Complete resolution of palpable hepatosplenomegaly \& all biopsy-proven or suspected SM-related organ damage PR is defined as all 3 criteria with response duration ≥12 weeks, that is not CR or progressive disease: * ≥ 50% reduction in neoplastic mast cells * Serum tryptase level reduced ≥50% * Resolution of 1+ biopsy-proven or suspected systemic mastocytosis (SM)-related organ damage findings CI is defined as any improvement in any of the above measures.

  Up to 6 months

Secondary Outcomes (10)

• Number of Participants With Adverse Events

  30 days

• Ibrutinib Pharmacokinetics (PK)

  28 days

• Change of Mast Cell Burden

  2 years

• Serum Tryptase Levels

  2 years

• Total Symptom Score (TSS)

  30 days

Study Arms (2)

Ibrutinib 420 mg/day

EXPERIMENTAL

Participants receive ibrutinib daily on days 1 to 28, at 420 mg/day in 28-day cycles

Drug: Ibrutinib

Ibrutinib 560 mg/day

EXPERIMENTAL

Participants receive ibrutinib daily on days 1 to 28, at 560 mg/day in 28-day cycles

Drug: Ibrutinib

Interventions

Ibrutinib DRUG

Given orally in 28-day cycles

Also known as: Imbruvica, PCI-32765, BTK Inhibitor PCI-32765, CRA-032765

Ibrutinib 420 mg/day; Ibrutinib 560 mg/day

Eligibility Criteria

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

You may qualify if:

• Diagnosis of systemic mastocytosis per 2008 World Health Organization (WHO) criteria. Those with advanced systemic mastocytosis (ASM); mast cell leukemia (MCL); or systemic mastocytosis-associated hematological clonal non-mast cell lineage disease (SM-AHNMD) required to have at least 1 organ damage finding
• Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 3.0 x upper limit of normal (ULN); if considered related to ASM/MCL ≤ 5 x ULN
• Estimated creatinine clearance ≥ 30 mL/min (Cockcroft-Gault)
• Total bilirubin ≤ 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin); if considered related to ASM/MCL ≤ 3 x ULN
• Female subjects must be of non-reproductive potential, or if of childbearing potential must have a negative serum pregnancy test upon study entry
• Must agree to use highly effective methods of birth control
• Written informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3
• Life expectancy \> 12 weeks

You may not qualify if:

• Received any investigational agent, chemotherapy, interferon-alpha, or 2-chlorodeoxyadenosine (2-CdA, cladribine) within 30 days prior to day 1; or monoclonal antibody ≤ 6 weeks prior to first administration of study treatment (patients with an AHNMD with progressive leukocytosis who require control of their counts are permitted to receive hydroxyurea)
• Diagnosis of AHNMD requiring immediate cytoreductive therapy or targeted drugs (eg, acute myeloid leukemia \[AML\])
• History of other malignancies, except:
• Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before the first dose of study drug, and at low risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease
• Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc., or chronic administration \[\> 14 days\] of \> 10 mg/day of prednisone) within 28 days of the first dose of study drug
• Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug
• Systemic treatment for infection completed ≤ 14 days before the first dose of study drug
• Known bleeding disorders (eg, severe von Willebrand's disease) or severe hemophilia
• History of stroke or intracranial hemorrhage within 6 months prior to enrollment
• Known history of human immunodeficiency virus (HIV) or
• Active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV)
• Major surgery within 4 weeks of first dose of study drug
• Any life-threatening illness, medical condition, or organ system dysfunction that could compromise the subject's safety or put the study outcomes at undue risk

Sponsors & Collaborators

• Jason Robert Gotlib: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Stanford University Hospitals and Clinics

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Mastocytosis, Systemic; Leukemia, Mast-Cell

Interventions

ibrutinib

Condition Hierarchy (Ancestors)

Mastocytosis; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Mast Cell Activation Disorders; Immune System Diseases; Leukemia; Leukemia, Myeloid, Acute; Leukemia, Myeloid; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Jason Robert Gotlib, MD; Professor of Medicine (Hematology)
• Organization: Stanford University Medical Center

C.Langford@stanford.edu

650-498-6000

Study Officials

• Jason Gotlib

  Stanford University Hospitals and Clinics

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 24, 2015
• First Posted: April 14, 2015
• Study Start: March 1, 2015
• Primary Completion: November 4, 2016
• Study Completion: June 14, 2017
• Last Updated: September 20, 2018
• Results First Posted: September 20, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)