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

NCT03225716

Description:

This research study is studying Ulocuplumab combined with ibrutinib as a possible treatment for symptomatic Waldenstrom's Macroglobulinemia (WM).

Related Conditions:
  • Waldenstrom Macroglobulinemia
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Ulocuplumab And Ibrutinib in Symptomatic Patients With Mutated CXCR4 Waldenstrom's Macroglobulinemia
  • Official Title: A Phase 1/2 Study of Ulocuplumab And Ibrutinib in Symptomatic Patients With Mutated CXCR4 Waldenstrom's Macroglobulinemia

Clinical Trial IDs

  • ORG STUDY ID: 17-235
  • NCT ID: NCT03225716

Conditions

  • Waldenstrom's Macroglobulinemia

Interventions

DrugSynonymsArms
UlocuplumabBMS-936564Ibrutinib + Ulocuplumab
IbrutinibImbruvicaIbrutinib + Ulocuplumab

Purpose

This research study is studying Ulocuplumab combined with ibrutinib as a possible treatment for symptomatic Waldenstrom's Macroglobulinemia (WM).

Detailed Description

      This is a Phase I/II clinical trial. A Phase I clinical trial tests the safety of an
      investigational drug and also tries to define the appropriate dose of the investigational
      drug to use for further studies. "Investigational" means that the drug is being studied.

      The FDA (the U.S. Food and Drug Administration) has not approved Ulocuplumab as a treatment
      for any disease. Ulocuplumab is a type of protein called an antibody that attacks CXCR4, a
      protein that is found on B-cells like WM.

      The FDA (the U.S. Food and Drug Administration) has Ibrutinib as a treatment option for this
      disease.

      Ibrutinib has been under investigation in research studies in participants with recurrent
      B-cell lymphoma, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), mantle
      cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and prolymphocytic leukemia, and
      WM. In a study of ibrutinib in relapsed/refractory WM patients, response rates were high and
      the treatment was well tolerated. In that study participants who had a CXCR4 mutation had a
      lower response rate to ibrutinib than those without a mutation.

      In this research study, the investigators are evaluating the safety of ulocuplumab in
      combination with ibrutinib participants with symptomatic WM who have a CXCR4 mutation. The
      investigators are also evaluating how well the ulocuplumab works in combination with
      ibrutinib
    

Trial Arms

NameTypeDescriptionInterventions
Ibrutinib + UlocuplumabExperimentalIbrutinib administered orally once daily Ulocuplumab administered intravenously 2-4 times per cycle for Cycles 1-6
  • Ulocuplumab
  • Ibrutinib

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose of Ulocuplumab
Time Frame:1 year
Safety Issue:
Description:Determine the maximum dose or maximum tolerated dose from the Phase I dose escalation based on the number of dose limiting toxicities in each cohort.

Secondary Outcome Measures

Measure:Time to Minor Response
Time Frame:2 years
Safety Issue:
Description:Time in months to >25%-50% reduction in serum IgM from baseline
Measure:Time to Major Response
Time Frame:2 years
Safety Issue:
Description:Time in months to >50-90% reduction in serum IgM from baseline
Measure:Time to Progression
Time Frame:2 years
Safety Issue:
Description:Time in months until >25% increase in serum IgM from nadir
Measure:Overall Response Rate
Time Frame:2 years
Safety Issue:
Description:Overall Response Rate= Minor response (>25%-50% reduction in serum IgM from baseline) + Partial Response (>50-90% reduction in serum IgM from baseline) + Very Good Partial Response (>90% reduction in serum IgM from baseline) + Complete Response (resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly).

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Waldenstrom's Macroglobulinemia

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