A Study of TRU-016 in Combination With Rituximab and Bendamustine in Subjects With Relapsed Indolent Lymphoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Emergent Product Development Seattle LLC
ClinicalTrials.gov Identifier:
NCT01317901
First received: March 15, 2011
Last updated: August 1, 2013
Last verified: November 2012
  Purpose

This is a Phase 1b/2 multicenter, open-label study of bendamustine, rituximab and TRU-016 (BRT) in subjects with relapsed indolent B-cell lymphoma. Phase 1b was an open-label, non-randomized, multiple-dose escalation study to determine the MTD of TRU-016 given in combination with rituximab and bendamustine and to determine a safe dosing regimen for the combination in up to 12 subjects with relapsed indolent lymphoma.

The Phase 2 portion, an open-label, randomized study to evaluate the efficacy of BRT compared with BR, was not conducted.


Condition Intervention Phase
B-cell Small Lymphocytic Lymphoma Recurrent
Drug: TRU-016
Drug: bendamustine + rituximab
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Study of TRU-016 in Combination With Rituximab and Bendamustine in Subjects With Relapsed Indolent Lymphoma

Resource links provided by NLM:


Further study details as provided by Emergent Product Development Seattle LLC:

Primary Outcome Measures:
  • Phase 1b:incidence of dose limiting toxicities during cycle 1 of each dose cohort to determine Maximum Tolerated Dose of TRU-016 [ Time Frame: Cycle 1 (28 days) ] [ Designated as safety issue: Yes ]
    A dose limiting toxicity is Grade 4 hematological toxicity that has not resolved to </= to Grade 2 within 2 weeks, >/=Grade 3 non-hematological adverse event (with some exceptions), Grade 3 nausea for > 5 days, Grade 4 febrile neutropenia, infusion reaction, Grade 5 toxicities


Secondary Outcome Measures:
  • Phase 1b: safety, immunogenicity and efficacy of TRU-016 when combined with bendamustine and rituximab, pharmacokinetics and pharmacodynamics of TRU-016 when combined with rituximab and bendamustine [ Time Frame: 60 days following last dose (max 6 28-day cycles) ] [ Designated as safety issue: No ]
    Efficacy is assessed using the Revised Response Criteria for Malignant Lymphoma. Complete response rate will also be assessed. Pharmacodynamic endpoints are changes from baseline in levels of T cells, B cells and NK cells,cytokines and chemokines, and in levels of CD37 expression on peripheral blood cells.


Enrollment: 12
Study Start Date: May 2011
Study Completion Date: June 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TRU-016+bendamustine+rituximab Drug: TRU-016
100 mg TRU-016 lyophilized solution for infusion at 10 or 20 mg/kg (or 6 mg/kg, if necessary) on Days 1 and 15 of each 28 day cycle
Active Comparator: bendamustine+rituximab
Phase 2 portion only
Drug: bendamustine + rituximab
Rituximab by IV administration at 375 mg/m^2 on Day 2, and bendamustine by IV on Days 1 and 2 of each 28 day cycle.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Age 18 years or older
  2. Histologically confirmed diagnosis of indolent non-Hodgkin's B-cell lymphoma (ie, follicular lymphoma, small lymphocytic lymphoma, and marginal zone lymphoma) that has relapsed (relapsed is defined as confirmed progressive disease [PD] after receiving the most recent prior therapy, or failure to achieve at least a PR while receiving the most recent prior therapy)
  3. At least one prior line of therapy for indolent lymphoma
  4. Bi-dimensionally measurable disease with at least one lesion measuring >=1.5 cm in a single dimension
  5. Eastern Cooperative Oncology Group (ECOG) performance status of <= 2
  6. Creatinine clearance of >40 mL/min as calculated by the

Cockcroft-Gault method as follows:

(140 - age) * (weight in kg [* 0.85 if female] / 72 * serum creatinine level) 7. Adequate hepatic function, indicated as follows:

  • aspartate aminotransferase (AST) of <2.5 x upper limit of normal (ULN)
  • alanine aminotransferase (ALT) of <2.5 x ULN
  • total bilirubin of <= 1.5 x ULN 8. Absolute neutrophil count (ANC) >=1000/mm3 (1000/µL) 9. Platelet count >= 100,000/mm3 10. Female subjects of child-bearing potential and male subjects must use an acceptable form of birth control for the duration of their study participation and for 6 months after completing study drug dosing; acceptable forms of birth control, unless dictated otherwise by local regulatory authorities 11. For women of childbearing potential, a negative serum pregnancy test result obtained during the screening period and a negative urine pregnancy test result within 24 hours before first administration of study drug 12. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information

Exclusion Criteria

  1. Diagnosis of grade 3b follicular lymphoma or transformed lymphoma of any grade
  2. Previously received TRU-016
  3. Prior treatment with rituximab if subject discontinued rituximab due to unresolved toxicity
  4. Refractory to bendamustine, defined as follows:

    • progression within 6 months of last dose of bendamustine
    • failed to achieve at least a PR while receiving bendamustine
    • discontinued bendamustine due to toxicity
    • received bendamustine within 6 months prior to first dose of study drug
  5. Received chemotherapy, radiotherapy, or immunotherapy including investigational agents within 28 days prior to the first dose of study drug
  6. Received therapeutic corticosteroids at doses equivalent to >10 mg prednisone per day for longer than 5 days within 14 days prior to the first dose of study drug, except if needed as a pre-medication
  7. Received filgrastim or equivalent within 14 days prior to screening (ie, collection of samples for laboratory tests) or pegfilgrastim within 28 days prior to screening (ie, collection of samples for laboratory tests)
  8. Prior allogeneic bone marrow transplant
  9. Prior autologous bone marrow transplant within 12 months prior to the first dose of study drug
  10. Received blood or platelet infusion within 7 days prior to screening (ie, collection of samples for laboratory tests)
  11. Previous or concurrent additional malignancy except non-invasive, non-melanomatous skin cancer or in situ carcinoma of the cervix, or other solid tumors if the subject has been disease-free for a minimum of 2 years prior to the first dose of study drug
  12. Known central nervous system or leptomeningeal lymphoma
  13. Any significant concurrent medical diseases or conditions, including but not limited to the following:

    • Clinically significant pulmonary dysfunction requiring oxygen therapy
    • An active infection (viral, bacterial, or fungal) requiring systemic therapy; subjects receiving prophylactic therapy are eligible
  14. Known allergy to mannitol
  15. History of positive serology for human immunodeficiency virus (HIV)
  16. Positive serology for hepatitis B (surface antigen or core antibody) Note: If a positive test result for hepatitis B core antibody is due to immunoglobulin treatment, the subject may be enrolled if the hepatitis B viral deoxyribonucleic acid (DNA) is negative.
  17. Positive serology for hepatitis C
  18. Pregnant or breastfeeding
  19. Other severe, acute, or chronic medical or psychiatric condition, laboratory abnormality, or difficulty complying with protocol requirements that may increase the risk associated with study participation or study drug administration or may interfere with safety
  20. Any condition that, in the investigator's opinion, makes the subject unsuitable for study participation
  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: NCT01317901

Locations
United States, Alabama
Site Reference ID/Investigator# 61543
Birmingham, Alabama, United States, 35294
United States, Georgia
Site Reference ID/Investigator# 61542
Augusta, Georgia, United States, 30912
United States, Nebraska
Site Reference ID/Investigator# 61523
Omaha, Nebraska, United States, 68114
United States, New Jersey
Site Reference ID/Investigator# 61522
Hackensack, New Jersey, United States, 07601
United States, North Carolina
Site Reference ID/Investigator# 61544
Chapel Hill, North Carolina, United States, 27599-7305
United States, Washington
Site Reference ID/Investigator# 61524
Seattle, Washington, United States, 98109-1023
Sponsors and Collaborators
Emergent Product Development Seattle LLC
Investigators
Study Director: Scott Stromatt, MD Emergent Product Development Seattle LLC
  More Information

No publications provided

Responsible Party: Emergent Product Development Seattle LLC
ClinicalTrials.gov Identifier: NCT01317901     History of Changes
Other Study ID Numbers: 16011
Study First Received: March 15, 2011
Last Updated: August 1, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Emergent Product Development Seattle LLC:
follicular lymphoma
small lymphocytic lymphoma
marginal zone lymphoma
non-Hodgkin's lymphoma
indolent lymphoma
NHL

Additional relevant MeSH terms:
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma
Leukemia, B-Cell
Leukemia, Lymphoid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Bendamustine
Nitrogen Mustard Compounds
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014