Daratumumab in Treating Patients with Relapsed or Refractory Waldenstrom Macroglobulinemia
This phase II trials studies how well daratumumab works in treating patients with Waldenstrom macroglobulinemia that has come back (relapsed) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as daratumumab, may induce changes in body’s immune system and may interfere with the ability of tumor cells to grow and spread.
Inclusion Criteria
- Clinicopathological diagnosis of Waldenstrom macroglobulinemia, and meeting criteria for treatment using consensus panel criteria from the Second International Workshop on Waldenstrom macroglobulinemia
- Bone marrow at screening positive for CD38 expression by flow cytometry and/or immunohistochemistry
- At least one previous treatment for WM with either documented disease progression or no response (stable disease) to the most recent treatment regimen
- 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
- Participants with symptomatic hyperviscosity or serum IgM > 5,000 mg/dL to undergo plasmapheresis prior to treatment initiation
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Absolute neutrophil count >= 1,000/mcL
- Platelets >= 50,000/mcL
- Hemoglobin >= 8 g/dL
- Total bilirubin =< 1.5 mg/dL or < 2 mg/dL if attributable to hepatic infiltration by neoplastic disease
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x institutional upper limit of normal
- Estimated glomerular filtration rate (EGFR) >= 30 ml/min
- Not on any active therapy for other malignancies with the exception of topical therapies for basal cell or squamous cell cancers of the skin; participants progressing on ibrutinib therapy (or other BTK inhibitor) may continue on therapy through screening, stopping at least 1 day prior to cycle 1 day 1
- 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 90 days after discontinuation from the study; FCBP must be referred to a qualified provider of contraceptive methods if needed; FCBP must have a negative serum pregnancy test at screening
- Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy
- 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
- 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 central nervous system (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), including participants with positive hepatitis B virus surface antigen (HBsAg) testing at screening; participants with evidence of resolved infection (i.e. who are HBsAg negative but positive for antibodies to hepatitis B core antigen (anti-HBc) and/or antibodies to hepatitis B surface antigen (anti-HBs) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels; those who are PCR positive are excluded. EXCEPTION: Participants with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR
- Active infection with hepatitis C virus (HCV) (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy)
- Lactating or pregnant women
- Grade >= 2 toxicity (other than alopecia) continuing from prior anti-cancer therapy
- History of non-compliance to medical regimens
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03187262.
PRIMARY OBJECTIVE:
I. To assess the best overall response rate (ORR) (> 25% reduction in disease burden) to single agent daratumumab in relapsed or refractory Waldenstrom macroglobulinemia (WM) patients at any point on therapy.
SECONDARY OBJECTIVES:
I. To assess the minor, partial, very good partial and complete response rate to single agent daratumumab in relapsed or refractory WM patients.
II. To determine progression free survival (PFS) following daratumumab in relapsed or refractory WM patients.
III. To evaluate the safety profile of daratumumab in patients with relapsed or refractory WM patients.
EXPLORATORY OBJECTIVE:
I. To observe differences (if any) in overall and major responses (partial response [PR] or better) attainment, and time to response based on tumor CD38 expression, and MYD88 and CXCR4 genotype.
OUTLINE:
INDUCTION: Patients receive daratumumab intravenously (IV) on days 1, 8, 15, and 22. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Beginning 2 weeks after induction, patients receive daratumumab IV on days 1 and 15. Treatment repeats every 28 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Beginning 4 weeks after the 8th infusion of consolidation, patients receive daratumumab IV on day 1. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 12 weeks for up to 24 months.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationDana-Farber Harvard Cancer Center
Principal InvestigatorJorge Julio Castillo
- Primary ID17-164
- Secondary IDsNCI-2017-02336
- ClinicalTrials.gov IDNCT03187262