Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03225716
Recruitment Status : Active, not recruiting
First Posted : July 21, 2017
Last Update Posted : February 5, 2020
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Steven P. Treon, MD, PhD, Dana-Farber Cancer Institute

Tracking Information
First Submitted Date  ICMJE June 29, 2017
First Posted Date  ICMJE July 21, 2017
Last Update Posted Date February 5, 2020
Actual Study Start Date  ICMJE October 20, 2017
Estimated Primary Completion Date January 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 20, 2017)
  • 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)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 20, 2017)
  • 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).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Ulocuplumab And Ibrutinib in Symptomatic Patients With Mutated CXCR4 Waldenstrom's Macroglobulinemia
Official Title  ICMJE A Phase 1/2 Study of Ulocuplumab And Ibrutinib in Symptomatic Patients With Mutated CXCR4 Waldenstrom's Macroglobulinemia
Brief Summary 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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Waldenstrom's Macroglobulinemia
Intervention  ICMJE
  • 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
Study Arms  ICMJE Experimental: Ibrutinib + Ulocuplumab
  • Ibrutinib administered orally once daily
  • Ulocuplumab administered intravenously 2-4 times per cycle for Cycles 1-6
Interventions:
  • Drug: Ulocuplumab
  • Drug: Ibrutinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 3, 2020)
13
Original Estimated Enrollment  ICMJE
 (submitted: July 20, 2017)
38
Estimated Study Completion Date  ICMJE January 31, 2025
Estimated Primary Completion Date January 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03225716
Other Study ID Numbers  ICMJE 17-235
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Steven P. Treon, MD, PhD, Dana-Farber Cancer Institute
Study Sponsor  ICMJE Dana-Farber Cancer Institute
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE
Principal Investigator: Steven P. Treon, MD, PhD Dana-Farber Cancer Institute
PRS Account Dana-Farber Cancer Institute
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP