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Trial record 2 of 16 for:    ibrutinib waldenstrom

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

This study is not yet open for participant recruitment.
Verified September 2017 by Steven P. Treon, MD, PhD, Dana-Farber Cancer Institute
Sponsor:
ClinicalTrials.gov Identifier:
NCT03225716
First Posted: July 21, 2017
Last Update Posted: September 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Steven P. Treon, MD, PhD, Dana-Farber Cancer Institute
  Purpose
This research study is studying Ulocuplumab combined with ibrutinib as a possible treatment for symptomatic Waldenstrom's Macroglobulinemia (WM).

Condition Intervention Phase
Waldenstrom's Macroglobulinemia Drug: Ulocuplumab Drug: Ibrutinib Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of Ulocuplumab And Ibrutinib in Symptomatic Patients With Mutated CXCR4 Waldenstrom's Macroglobulinemia

Resource links provided by NLM:


Further study details as provided by Steven P. Treon, MD, PhD, Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Maximum Tolerated Dose of Ulocuplumab [ Time Frame: 1 year ]
    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.

  • Major Response Rate [ Time Frame: 2 years ]
    Major Response Rate= Partial response (>50% 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)


Secondary Outcome Measures:
  • Time to Minor Response [ Time Frame: 2 years ]
    Time in months to >25%-50% reduction in serum IgM from baseline

  • Time to Major Response [ Time Frame: 2 years ]
    Time in months to >50-90% reduction in serum IgM from baseline

  • Time to Progression [ Time Frame: 2 years ]
    Time in months until >25% increase in serum IgM from nadir

  • Overall Response Rate [ Time Frame: 2 years ]
    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).


Estimated Enrollment: 38
Anticipated Study Start Date: September 30, 2017
Estimated Study Completion Date: January 31, 2025
Estimated Primary Completion Date: January 31, 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ibrutinib + Ulocuplumab
  • Ibrutinib administered orally once daily
  • Ulocuplumab administered intravenously 2-4 times per cycle for Cycles 1-6
Drug: Ulocuplumab
Ulocuplumab is a type of protein called an antibody that attacks CXCR4
Other Name: BMS-936564
Drug: Ibrutinib
Ibrutinib small-molecule inhibitor of Bruton's tyrosine kinase (BTK) with potential antineoplastic activity
Other Name: Imbruvica

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

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03225716


Contacts
Contact: Steven P. Treon, MD, PhD 617-632-2681 steven_treon@dfci.harvard.edu

Locations
United States, Massachusetts
Dana Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Steven P. Treon, MD, PhD    617-632-2681    steven_treon@dfci.harvard.edu   
Principal Investigator: Steven P. Treon, MD, PhD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Bristol-Myers Squibb
Investigators
Principal Investigator: Steven P. Treon, MD, PhD Dana-Farber Cancer Institute
  More Information

Responsible Party: Steven P. Treon, MD, PhD, MD, PhD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT03225716     History of Changes
Other Study ID Numbers: 17-235
First Submitted: June 29, 2017
First Posted: July 21, 2017
Last Update Posted: September 6, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Steven P. Treon, MD, PhD, Dana-Farber Cancer Institute:
Waldenstrom's Macroglobulinemia

Additional relevant MeSH terms:
Waldenstrom Macroglobulinemia
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs