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

NCT01317901 | Completed Phase 1 Results DMC

• 1 other identifier: 16011
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

B-cell Small Lymphocytic Lymphoma Recurrent

Keywords

follicular lymphoma; small lymphocytic lymphoma; marginal zone lymphoma; non-Hodgkin's lymphoma; indolent lymphoma

Outcome Measures

Primary Outcomes (1)

• Response

  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.

  Day 15 and Day 28 of even-numbered cycles

Study Arms (1)

TRU-016+bendamustine+rituximab

EXPERIMENTAL

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.

Drug: TRU-016; Drug: Bendamustine; Drug: Rituximab

Interventions

TRU-016 DRUG

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

Also known as: otlertuzumab

TRU-016+bendamustine+rituximab

Bendamustine DRUG

Bendamustine by IV administration on Days 1 and 2 of each 28 day cycle.

Also known as: Treanda

TRU-016+bendamustine+rituximab

Rituximab DRUG

Rituximab by IV administration at 375 mg/m\^2 on Day 2 of each 28 day cycle.

Also known as: rituxan

TRU-016+bendamustine+rituximab

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older
• 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)
• At least one prior line of therapy for indolent lymphoma
• Bi-dimensionally measurable disease with at least one lesion measuring \>=1.5 cm in a single dimension
• Eastern Cooperative Oncology Group (ECOG) performance status of \<= 2
• 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

You may not qualify if:

• Diagnosis of grade 3b follicular lymphoma or transformed lymphoma of any grade
• Previously received TRU-016
• Prior treatment with rituximab if subject discontinued rituximab due to unresolved toxicity
• 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
• Received chemotherapy, radiotherapy, or immunotherapy including investigational agents within 28 days prior to the first dose of study drug
• 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
• 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)
• Prior allogeneic bone marrow transplant
• Prior autologous bone marrow transplant within 12 months prior to the first dose of study drug
• Received blood or platelet infusion within 7 days prior to screening (ie, collection of samples for laboratory tests)
• 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

Sponsors & Collaborators

• Aptevo Therapeutics: lead

Study Sites (6)

Site Reference ID/Investigator# 61543

Birmingham, Alabama, 35294, United States

Location

Site Reference ID/Investigator# 61542

Augusta, Georgia, 30912, United States

Location

Site Reference ID/Investigator# 61523

Omaha, Nebraska, 68114, United States

Location

Site Reference ID/Investigator# 61522

Hackensack, New Jersey, 07601, United States

Location

Site Reference ID/Investigator# 61544

Chapel Hill, North Carolina, 27599-7305, United States

Location

Site Reference ID/Investigator# 61524

Seattle, Washington, 98109-1023, United States

Location

Related Publications (1)

• 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.

  PMID: 24927856 BACKGROUND

MeSH Terms

Conditions

Lymphoma, Follicular; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Non-Hodgkin

Interventions

TRU 016; Bendamustine Hydrochloride; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Scott C. Stromatt
• Organization: Aptevo Therapeutics

sstromatt@apvo.com

206-859-6675

Study Officials

• Scott Stromatt, MD

  Aptevo Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2011
• First Posted: March 17, 2011
• Study Start: May 1, 2011
• Primary Completion: April 1, 2013
• Study Completion: June 1, 2013
• Last Updated: June 28, 2017
• Results First Posted: October 6, 2016

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)