An Efficacy and Safety Proof of Concept Study of Daratumumab in Relapsed/Refractory Mantle Cell Lymphoma, Diffuse Large B-Cell Lymphoma, and Follicular Lymphoma

• ClinicalTrials.gov Identifier: NCT02413489
• Recruitment Status: Terminated
• First Posted: April 10, 2015
• Results First Posted: June 26, 2018
• Last Update Posted: June 26, 2018
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular	Drug: Daratumumab	Phase 2

Detailed Description:

This is an open label (everyone knows the study intervention), Phase 2 study to evaluate efficacy and safety of daratumumab in relapsed or refractory mantle cell lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma. The study will have three phases. Screening phase, treatment phase, follow-up phase. Participants will receive daratumumab (16 milligram per kilogram [mg/kg]) as intravenous infusion approximately 3.5 years. Participants will primarily be assessed for overall response rate. Safety will be monitored throughout the study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label, Phase 2 Study to Evaluate Efficacy and Safety of Daratumumab in Relapsed or Refractory Mantle Cell Lymphoma, Diffuse Large B-Cell Lymphoma, and Follicular Lymphoma
• Actual Study Start Date: September 2, 2015
• Actual Primary Completion Date: June 1, 2017
• Actual Study Completion Date: June 1, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Daratumumab; Participants will receive daratumumab (16 milligram per kilogram [mg/kg]) as intravenous infusion 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.	Drug: Daratumumab; 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.

Outcome Measures

Primary Outcome Measures :

1. Overall Response Rate (ORR) [ Time Frame: After the first dose until disease progression, withdrawal of consent from study participation, or the end of study (approximately 1.9 years) ]
   ORR was defined as the percentage of participants who achieved complete response (CR) or partial response (PR). As per Revised Response Criteria for Malignant Lymphoma, Lymph node measurements were taken from Computed Tomography (CT), CT portion of the Positron Emission Tomography/Computed Tomography (PET/CT), or Magnetic resonance imaging (MRI) scans where applicable. CR is defined as complete disappearance of all evidence of disease; PR as a greater than (>) 50 percent (%) decrease in the sum of the products of the maximal perpendicular diameters of measured lesions (SPD) and no new sites.

Secondary Outcome Measures :

1. Duration of Response [ Time Frame: Approximately 1.9 years ]
   Duration of response was the duration from the date of the initial documentation of a response to the date of first documented evidence of progressive disease (PD). PD is defined as any new lesion >1.5 centimeter (cm) in any axis or greater than or equal to (>=) 50% increase in previously involved sites.
2. Progression Free Survival (PFS) [ Time Frame: Approximately 1.9 years ]
   PFS was defined as the duration from the date of the first daratumumab dose to the date of progression or death, whichever comes first.
3. Overall Survival (OS) [ Time Frame: Approximately 1.9 years ]
   Overall survival was defined as the duration from the date of the first daratumumab dose to the date of death.
4. Time to Response [ Time Frame: Approximately 1.9 years ]
   Time to response was defined as the duration from the date of the first dose of daratumumab to the earliest date that a response (CR/PR) is first documented.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

United States, California

Duarte, California, United States

Fountain Valley, California, United States

United States, Florida

Jacksonville, Florida, United States

Pembroke Pines, Florida, United States

United States, Georgia

Atlanta, Georgia, United States

United States, Illinois

Chicago, Illinois, United States

United States, Kentucky

Louisville, Kentucky, United States

United States, Maryland

Baltimore, Maryland, United States

United States, Minnesota

Rochester, Minnesota, United States

United States, Nebraska

Omaha, Nebraska, United States

United States, New Jersey

New Brunswick, New Jersey, United States

United States, Pennsylvania

Pittsburgh, Pennsylvania, United States

United States, Texas

Houston, Texas, United States

United States, Washington

Seattle, Washington, United States

Australia

Adelaide, Australia

Box Hill, Australia

Melbourne, Australia

Belgium

Brugge, Belgium

Gent, Belgium

France

Lille, France

Limoges Cedex, France

Nantes Cedex 01, France

Paris Cedex 10, France

Pessac, France

Pierre Benite, France

Rouen Cedex, France

Korea, Republic of

Goyang-Si, Korea, Republic of

Seoul, Korea, Republic of

Netherlands

Amsterdam, Netherlands

Rotterdam, Netherlands

Utrecht, Netherlands

Turkey

Ankara, Turkey

Atakum, Turkey

Istanbul, Turkey

Kocaeli, Turkey

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

  Study Documents (Full-Text)

Documents provided by Janssen Research & Development, LLC:

Study Protocol  [PDF] January 19, 2016

Statistical Analysis Plan  [PDF] May 16, 2017

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Salles G, Gopal AK, Minnema MC, Wakamiya K, Feng H, Schecter JM, Wang M. Phase 2 Study of Daratumumab in Relapsed/Refractory Mantle-Cell Lymphoma, Diffuse Large B-Cell Lymphoma, and Follicular Lymphoma. Clin Lymphoma Myeloma Leuk. 2019 May;19(5):275-284. doi: 10.1016/j.clml.2018.12.013. Epub 2019 Jan 2.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT02413489
• Other Study ID Numbers: CR106660; 54767414LYM2001 ( Other Identifier: Janssen Research & Development, LLC ); 2014-005299-26 ( EudraCT Number )
• First Posted: April 10, 2015
• Results First Posted: June 26, 2018
• Last Update Posted: June 26, 2018
• Last Verified: May 2018

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

Keywords provided by Janssen Research & Development, LLC:

Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Daratumumab

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Daratumumab; Antineoplastic Agents