Try our beta test site

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):
Aptevo Therapeutics
ClinicalTrials.gov Identifier:
NCT01317901
First received: March 15, 2011
Last updated: January 31, 2017
Last verified: January 2017

March 15, 2011
January 31, 2017
May 2011
April 2013   (Final data collection date for primary outcome measure)
Response [ Time Frame: Day 15 and Day 28 of even-numbered cycles ]
Response was assessed by the investigator on the basis of clinical, radiological, and pathological (i.e., bone marrow) criteria, using the IWG criteria (Cheson et al 2007). A CR is a complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. A PR is at least a 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses, no increase should be observed in the size of other nodes, liver or spleen, and no new sites of disease should be observed.
  • 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) ]
  • 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 ]
Complete list of historical versions of study NCT01317901 on ClinicalTrials.gov Archive Site
Not Provided
  • safety of TRU-016 in combination with rituximab and bendamustine [ Time Frame: approximately 6 months ]
    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 ]
    secondary efficacy endpoints as measured by the Objective Response Rate (percentage of subjects with a Complete Response or a Partial Response); Progression Free Survival; Overall Survival and Duration of Objective Response
  • determine pharmacokinetics and pharmacodynamics [ Time Frame: approximately 6 months ]
    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 1 Study of TRU-016 in Combination With Rituximab and Bendamustine in Subjects With Relapsed Indolent Lymphoma

This was a Phase 1 multicenter study of bendamustine, rituximab and TRU-016 (BRT) in subjects with relapsed indolent B-cell lymphoma. This was a multiple-dose escalation study to determine the maximum-tolerated dose (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 originally planned Phase 2 portion, an open-label, randomized study to evaluate the efficacy of BRT compared with BR, was not conducted.

This study was planned to be conducted in 2 parts: a Phase 1b component designed to determine a safe dosing regimen, and a Phase 2 component designed to evaluate the efficacy of BRT compared to BR in subjects with relapsed indolent lymphoma. The Phase 2 component was not conducted.

This was an open-label, non randomized, multiple-dose escalation study to determine the MTD of BRT and to determine a safe dosing regimen for the combination in subjects with relapsed indolent lymphoma.

The study consisted of a screening period lasting up to 21 days, a treatment period lasting up to 6 cycles (28 days each), and a 60-day follow-up period. Up to 12 subjects (2 cohorts of 6 subjects each) were planned for enrollment. Two dose levels (10 and 20 mg/kg) of TRU-016 combined with rituximab 375 mg/m2 and bendamustine 90 mg/m2 were evaluated during up to 6 cycles (28 days each). TRU-016 was administered by intravenous (IV) infusion on Days 1 and 15 of each cycle. Rituximab was administered by IV infusion on Day 2 of each cycle. Bendamustine was administered by IV infusion on Days 1 and 2 of each cycle. Subjects received study treatment for up to 6 cycles.

Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: No masking
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
    Other Name: otlertuzumab
  • Drug: Bendamustine
    Bendamustine by IV administration on Days 1 and 2 of each 28 day cycle.
    Other Name: Treanda
  • Drug: Rituximab
    Rituximab by IV administration at 375 mg/m^2 on Day 2 of each 28 day cycle.
    Other Name: rituxan
Experimental: TRU-016+bendamustine+rituximab
Two dose levels (10 and 20 mg/kg) of TRU 016 combined with rituximab 375 mg/m2 and bendamustine 90 mg/m2 were evaluated during up to 6 cycles (28 days each). TRU-016 was administered by intravenous (IV) infusion on Days 1 and 15 of each cycle. Rituximab was administered by IV infusion on Day 2 of each cycle. Bendamustine was administered by IV infusion on Days 1 and 2 of each cycle. Subjects received study treatment for up to 6 cycles.
Interventions:
  • Drug: TRU-016
  • Drug: Bendamustine
  • Drug: Rituximab
Gopal AK, Tarantolo SR, Bellam N, Green DJ, Griffin M, Feldman T, Mato AR, Eisenfeld AJ, Stromatt SC, Goy A. Phase 1b study of otlertuzumab (TRU-016), an anti-CD37 monospecific ADAPTIR™ therapeutic protein, in combination with rituximab and bendamustine in relapsed indolent lymphoma patients. Invest New Drugs. 2014 Dec;32(6):1213-25. doi: 10.1007/s10637-014-0125-2. Epub 2014 Jun 15.

*   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 partial response (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
Sexes Eligible for Study: All
18 Years to 99 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01317901
16011
Yes
Not Provided
No
Not Provided
Aptevo Therapeutics
Aptevo Therapeutics
Not Provided
Study Director: Scott Stromatt, MD Aptevo Therapeutics
Aptevo Therapeutics
January 2017

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