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
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.
