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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2016 by Janssen Research & Development, LLC
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT02413489
First received: April 7, 2015
Last updated: December 16, 2016
Last verified: December 2016
  Purpose
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 Intervention Phase
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Follicular
Drug: Daratumumab
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Number of Participants With Overall response rate (ORR) [ Time Frame: Approximately 3.5 years ]
    The ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR).


Secondary Outcome Measures:
  • Duration of response (DoR) [ Time Frame: Approximately 3.5 years ]
    Duration of response (DoR) will be duration from the date of the initial documentation of a response to the date of first documented evidence of PD (or relapse for participants who experience CR). For those participants who are still without progression/relapse, DoR will be censored at the last adequate tumor assessment.

  • Progression Free Survival (PFS) [ Time Frame: Approximately 3.5 years ]
    The PFS is defined as the duration from the date of the first daratumumab dose to the date of Progression/relapse or death, whichever comes first. For those participants who are still alive without progression/relapse, PFS will be censored at the last adequate tumor assessment.

  • Overall survival (OS) [ Time Frame: Approximately 3.5 years ]
    Overall survival (OS) is defined as the duration from the date of the first daratumumab dose to the date of death. For those participants who are still alive without progression/relapse, OS will be censored at the last date known to be alive.

  • Time to response [ Time Frame: Approximately 3.5 years ]
    Time to response is 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. For non-responders, it will be censored at the date of progressive disease/relapse or the date of the last adequate disease assessment, whichever comes first.


Estimated Enrollment: 210
Study Start Date: September 2015
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: January 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02413489

Contacts
Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: JNJ.CT@sylogent.com

  Show 40 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Additional Information:
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02413489     History of Changes
Other Study ID Numbers: CR106660
54767414LYM2001 ( Other Identifier: Janssen Research & Development, LLC )
2014-005299-26 ( EudraCT Number )
Study First Received: April 7, 2015
Last Updated: December 16, 2016

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, B-Cell
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
Daratumumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on March 28, 2017