Clinical Trial - NCT03225716

A Study of Ulocuplumab And Ibrutinib in Symptomatic Patients With Mutated CXCR4 Waldenstrom's Macroglobulinemia

Recruiting

Sponsor: Dana-Farber Cancer Institute

Collaborators: Bristol-Myers Squibb

Information provided by (Responsible party): Principal Investigator Dana-Farber Cancer Institute Steven P. Treon, MD, PhD MD, PhD

ClinicalTrials.gov Identifier: NCT03225716

Protocol Info

Short Description: Phase 1/2 Ulocuplumab + Ibrutinib in Waldenstrom's Macroglobulinemia
Long Description: A Phase 1/2 Study of Ulocuplumab And Ibrutinib in symptomatic patients with mutated CXCR4 Waldenstrom’s Macroglobulinemia
MGH Status: Open
Sponsor: DF/HCC
Disease Program: M. Myeloma

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.




Purpose

This research study is studying Ulocuplumab combined with ibrutinib as a possible treatment for symptomatic Waldenstrom's Macroglobulinemia (WM).
Condition Title Intervention Phase
Waldenstrom's Macroglobulinemia Ulocuplumab Ibrutinib Phase 1/Phase 2
Study Type Interventional
Official Title A Phase 1/2 Study of Ulocuplumab And Ibrutinib in Symptomatic Patients With Mutated CXCR4 Waldenstrom's Macroglobulinemia

Primary Outcome Measures

Maximum Tolerated Dose of Ulocuplumab [Time Frame: 1 year] [Designated as safety issue: ]

Major Response Rate [Time Frame: 2 years] [Designated as safety issue: ]


Secondary Outcome Measures

Time to Minor Response [Time Frame: 2 years] [Designated as safety issue: ]

Time to Major Response [Time Frame: 2 years] [Designated as safety issue: ]

Time to Progression [Time Frame: 2 years] [Designated as safety issue: ]

Overall Response Rate [Time Frame: 2 years] [Designated as safety issue: ]

Estimated Enrollment: 38
Study Start Date: October 2017
Estimated Study Completion Date: January 2025
Estimated Primary Completion Date: January 2021
Arms Assigned Interventions

Experimental:Ibrutinib + Ulocuplumab

Ibrutinib administered orally once daily Ulocuplumab administered intravenously 2-4 times per cycle for Cycles 1-6
Drug:Ibrutinib
Ibrutinib small-molecule inhibitor of Bruton's tyrosine kinase (BTK) with potential antineoplastic activity

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

Inclusion Criteria:

  • Clinicopathological diagnosis of Waldenstrom's Macroglobulinemia and meeting criteria for treatment using consensus panel criteria from the Second International Workshop on Waldenstrom's macroglobulinemia (Kyle et al, 2003) or have high risk disease with an serum IgM level of 6,000 mg or higher (Gustine et al, 2016).
  • MYD88 and CXCR4 mutated disease (determined by Treon laboratory or molecular diagnostics laboratory).
  • Measurable disease, defined as presence of serum immunoglobulin M (IgM) with a minimum IgM level of >2 times the upper limit of normal of each institution is required.
  • Age ≥ 18 years
  • ECOG performance status < or = 2 (see Appendix A.).
  • To establish eligibility, participants must have adequate organ and marrow function as defined below:
  • Absolute neutrophil count ≥ 1,000/uL
  • Platelets ≥ 75,000/uL
  • Hemoglobin ≥ 8 g/dL
  • Total bilirubin ≤ 1.5 mg/dL or < 2 mg/dL if attributable to hepatic infiltration by neoplastic disease or Gilbert's syndrome
  • AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional upper limit of normal
  • Creatinine ≤ 2 mg/dL
  • Not on any active therapy for other malignancies with the exception of topical therapies for basal cell or squamous cell cancers of the skin.
  • Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or have or will have complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) while participating in the study; and 2) for at least 28 days after discontinuation from the study. Men must agree to use a latex condom during sexual contact with a FCBP even if the participants have had a successful vasectomy. FCBP must be referred to a qualified provider of contraceptive methods if needed. FCBP must have a negative serum pregnancy test at screening.
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Any serious medical condition, laboratory abnormality, uncontrolled intercurrent illness, or psychiatric illness/social condition that would prevent study participation.
  • Concurrent use of any other anti-cancer agents or treatments or any other investigational agents.
  • Treatment with strong CYP3A4/5 and/or CYP2D6 inhibitors
  • Prior exposure to ibrutinib or ulocuplumab
  • With the exception of low-dose aspirin, subjects enrolled in this study should not take concomitant medications that durably inhibit platelet function including marine oil tablets. For such medications a wash-out period of ≥ 7 days is required prior to starting treatment. Agents which inhibit platelet function transiently or inhibit coagulation by other mechanisms are restricted (e.g. use with caution). Medications that directly and durably inhibit platelet function include aspirin containing combinations, clopidogrel, dipyridamole, tirofiban, epoprostenol, eptifibatide, cilostazol, abciximab, ticlopidine, cilostazol.
  • Participants should not take drugs that directly and durably inhibit coagulation with the exception of warfarin (coumadin) and heparin including low-molecular-weight heparin (LMWH), including enoxaparin, tinzaparin, etc.
  • Any condition, including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
  • Known CNS lymphoma.
  • New York Heart Association classification III or IV heart failure.
  • Known history of Human Immunodeficiency Virus (HIV), active infection with Hepatitis B Virus (HBV), and/or Hepatitis C Virus (HCV).
  • Lactating or pregnant women.
  • Grade > 2 toxicity (other than alopecia) continuing from prior anti-cancer therapy.
  • Inability to swallow capsules
  • History of non-compliance to medical regimens.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03225716

Locations

  • United States, Massachusetts
    • Dana Farber Cancer Institute Boston, Massachusetts, United States, 02215

Sponsors and Collaborators

Dana-Farber Cancer Institute

Bristol-Myers Squibb

More Information

No publications provided

Responsible Party: Principal Investigator Dana-Farber Cancer Institute Steven P. Treon, MD, PhD MD, PhD
ClinicalTrials.gov Identifier: NCT03225716
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Dana-Farber Cancer Institute:

Waldenstrom's Macroglobulinemia

Additional relevant MeSH terms:

Waldenstrom Macroglobulinemia

Antibodies, Monoclonal

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on August 15, 2019