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

March 15, 2011
August 1, 2013
May 2011
April 2013   (final data collection date for primary outcome measure)
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
  • the incidence of dose limiting toxicities during cycle 1 of each dose cohort to determine Maximum Tolerated Dose of TRU-016 (Phase 1 only) [ Time Frame: Cycle 1 (28 days) ] [ Designated as safety issue: Yes ]
  • efficacy as measured by the Complete Response Rate of TRU-016 in combination with rituximab and bendamustine (Phase 2 portion only) [ Time Frame: approximately 6 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01317901 on ClinicalTrials.gov Archive Site
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.
  • safety of TRU-016 in combination with rituximab and bendamustine [ Time Frame: approximately 6 months ] [ Designated as safety issue: Yes ]
    safety including the incidence of treatment-emergent adverse events and drug related adverse events, change from baseline in clinical laboratory results, vital signs and physical exams, and incidence of TRU-016 anti-drug antibodies.
  • efficacy of TRU-016 in combination with bendamustine and rituximab [ Time Frame: approximately 6 months ] [ Designated as safety issue: No ]
    secondary efficacy endpoints as measured by the Objective Response Rate (percentage of subjects with a Complete Response or a Partial Response); Progressions Free Survival; Overall Survival and Duration of Objective Response
  • determine pharmacokinetics and pharmacodynamics [ Time Frame: approximately 6 months ] [ Designated as safety issue: No ]
    PK (maximum serum concentration, area under the curve, clearance, distribution and half-life) and PD (change from baseline levels of T cells, B cells and NK cells, change from baseline in levels of CD37 expression/saturation, change from baseline in cytokines and chemokines and changes from baseline of quantitative immunoglobulins) of TRU-016 in combination with bendamustine and rituximab
Not Provided
Not Provided
 
A Study of TRU-016 in Combination With Rituximab and Bendamustine in Subjects With Relapsed Indolent Lymphoma
A Phase 1b/2 Study of TRU-016 in Combination With Rituximab and Bendamustine in Subjects With Relapsed Indolent Lymphoma

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.

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
B-cell Small Lymphocytic Lymphoma Recurrent
  • 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
  • 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.
  • Experimental: TRU-016+bendamustine+rituximab
    Intervention: Drug: TRU-016
  • Active Comparator: bendamustine+rituximab
    Phase 2 portion only
    Intervention: Drug: bendamustine + rituximab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
12
June 2013
April 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01317901
16011
Yes
Emergent Product Development Seattle LLC
Emergent Product Development Seattle LLC
Not Provided
Study Director: Scott Stromatt, MD Emergent Product Development Seattle LLC
Emergent Product Development Seattle LLC
November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP