An Efficacy and Safety Proof of Concept Study of Daratumumab in Relapsed/Refractory Mantle Cell Lymphoma, Diffuse Large B-Cell Lymphoma, and Follicular Lymphoma
Condition: Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular
MeSH terms: Lymphoma; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin
Intervention: Daratumumab
Intervention description: Daratumumab 16 mg/kg will be administered as intravenous infusion to participants once every week for 8 weeks; then once every other week for 16 weeks; thereafter once every 4 weeks until documented progression, unacceptable toxicity, or study end.
Intervention MeSH terms: Daratumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Daratumumab

Summary:

      The purpose of this study is to assess overall response rate [ORR, including complete
      response (CR) and partial response (PR)], of daratumumab in participants with non-Hodgkin's
      lymphoma [a cancer of the lymph nodes (or tissues)-NHL] and to evaluate association between
      ORR and CD38 expression level in order to determine a threshold for CD38 expression level in
      each NHL subtype, above which daratumumab activity is enhanced in participants with relapsed
      or refractory mantle cell lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has diagnosis and prior treatment for each non-hodgkin's lymphoma (NHL) subtype as
             defined below: Mantle cell lymphoma (MCL): pathologically verified diagnosis of MCL
             based on local pathology report, relapsed or refractory disease after at least 2 prior
             lines of therapy, including at least 1 cycle of Bruton's tyrosine kinase (BTK)
             inhibitor therapy and documented progressive disease (PD) during or after BTK
             inhibitor treatment or participants who could not tolerate BTK inhibitor [ie,
             discontinued BTK inhibitor due to adverse events (AEs)], b) Diffuse large B cell
             lymphoma (DLBCL): pathologically confirmed diagnosis of non-transformed DLBCL, and
             relapsed or refractory disease; for those participants who have not received HDT/ASCT
             are not eligible for HDT/ASCT due to comorbidities, c) Follicular lymphoma (FL):
             pathologically confirmed diagnosis of FL of Grade 1, 2, or 3a according to World
             Health Organization (WHO) criteria without pathological evidence of transformation,
             and relapsed disease after at least two prior systemic therapies including one
             anti-CD20 containing combination regimen

          -  At least 1 measurable site of disease

          -  Participants must have available archival or fresh tumor tissue or both to submit to a
             central laboratory for CD38 assay. Expression of CD38 is measured by
             immunohistochemistry on fresh or archived tumor sample by central assessment using a
             CD38 investigational IHC assay under development: a) Stage 1: participants whose
             tumors are more than or equal to (>=) 50 percent (%) positive for CD38, b) Stage 2:
             participant has less than (<) 50% CD38+ or greater than (>) 50% CD38+ depending on the
             distribution of CD 38 expression of enrolled participants during Stage 2. The sponsor
             will advise on which eligibility criterion is permitted during the enrollment period

          -  Participant must have an ECOG performance status score of 0 or 1

          -  Women of childbearing potential must be practicing a highly effective method of birth
             control consistent with local regulations regarding the use of birth control methods
             for participants participating in clinical studies: example, established use of oral,
             injected or implanted hormonal methods of contraception; placement of an intrauterine
             device (IUD) or intrauterine system (IUS); barrier methods: condom with spermicidal
             foam/gel/film/cream/suppository or occlusive cap (diaphragm or cervical/vault caps)
             with spermicidal foam/gel/film/cream/suppository; male partner sterilization (the
             vasectomized partner should be the sole partner for that participant); true abstinence
             (when this is in line with the preferred and usual lifestyle of the participant)
             during and after the study (3 months after the last dose of any component of the
             treatment regimen)

          -  A woman of childbearing potential must have a negative serum or urine pregnancy test
             within 14 days before commencing treatment. Females of reproductive potential must
             commit either to abstain continuously from heterosexual sexual intercourse or to use 2
             methods of reliable birth control simultaneously

          -  A man who is sexually active with a woman of childbearing potential and has not had a
             vasectomy must agree to use a barrier method of birth control example, either condom
             with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap
             (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository,
             and all men must also not donate sperm during the study and for 3 months after
             receiving the last dose of any component of the treatment regimen. The exception to
             this restriction is that if the participant's female partner is surgically sterile, a
             second method of birth control is not required

        Exclusion Criteria:

          -  Known central nervous system lymphoma

          -  Prior anti-tumor therapy including (all times measured prior to start of study drug):
             nitrosoureas within 6 weeks, chemotherapy within 3 weeks, therapeutic antibodies
             within 4 weeks, radio- or toxin-immunoconjugates within 10 weeks, radiation therapy
             within 2 weeks, investigational agents within 3 weeks, unless antibody this should be
             within 4 weeks

          -  Daratumumab or other anti-CD38 therapies

          -  Participant has a history of malignancy (other than NHL) within 3 years before the
             screening period (exceptions are squamous and basal cell carcinomas of the skin and
             carcinoma in situ of the cervix, non-muscle invasive bladder cancer (papillary
             neoplasms of low malignant potential and primary non-invasive tumors), or malignancy
             that in the opinion of the investigator, with concurrence with the sponsor's medical
             monitor, is considered cured with minimal risk of recurrence within 2 years)

          -  Participant has known chronic obstructive pulmonary disease (COPD) with a Forced
             Expiratory Volume in 1 second (FEV1) less than (<) 50% predicted normal. Note that
             FEV1 testing is required for participants suspected of having COPD and participants
             must be excluded if FEV1 <50% b) Participant has known moderate or severe persistent
             asthma within 2 years (see Attachment 4: NHLBI table of asthma severity), or currently
             has uncontrolled asthma of any classification. (Note that participants who currently
             have controlled intermittent asthma or controlled mild persistent asthma are allowed
             in the study)