Clinical trial NCT02271945: Safety/Efficacy of MEDI-551 in Combination With Immunomodulating Therapies in Subjects With Aggressive B-cell Lymphomas
Official title: A Phase 1b/2 Open-label Study to Evaluate the Safety/Efficacy of MEDI-551 in Combination With Immunomodulating Therapy in Subjects With Relapsed or Refractory Aggressive B-cell Lymphomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Relapsed/Refractory Aggressive B-cell Lymphomas
Keywords: aggressive lymphoma, DLBCL, NHL
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2014-10-22
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1b/2 open-label study to evaluate the safety/efficacy of MEDI-551 + MEDI0680 in participants with relapsed or refractory aggressive B-cell lymphomas who have failed 1-2 prior lines of therapy.

Detailed description: This is a Phase 1b/2, multicenter, open-label, study of MEDI-551 in combination with immunomodulating therapy evaluating the safety, tolerability, pharmacokinetics, immunogenicity and anti-tumor activity in subjects with relapsed or refractory aggressive B-cell lymphomas

Eligibility criteria: Key inclusion criteria:

* Histologically confirmed aggressive diffuse large B-cell lymphoma (DLBCL), including follicular lymphoma (FL) transforming to DLBCL, transformed indolent lymphoma, mantle cell lymphoma (MCL), or Grade 3B FL for dose-escalation cohorts. Only participants with DLBCL will be enrolled in the dose-expansion cohort.
* Willing to provide a fresh tumor sample
* Evaluable/measurable disease with measurable disease defined as greater than or equal to (\>= 1) lesion less than or equal to (\<=) 20 mm in one dimension or ≥ 15 mm in 2 dimensions as measured by conventional or high-resolution (spiral) computed tomography (CT). Disease evaluable by the International Working Group criteria (Cheson et al, 2007). (NOTE: Irradiated lesions will not be evaluable.)
* Baseline fludeoxyglucose positron emission tomography (FDG-PET) or FDG-PET/CT scans must show positive lesions compatible with CT-defined anatomical tumor sites.
* Relapsed from or refractory to \>= 2 prior chemotherapy regimens with \>= 1 regimen containing rituximab or failed 1 prior rituximab-containing regimen and unable to tolerate additional multiagent chemotherapy. NOTE: Subjects enrolled in the dose-escalation portion of the study must have exhausted all available standard therapy.
* At least 100 days past autologous stem cell transplant (ASCT).
* At least 1 year past allogeneic stem-cell transplant (SCT) and off immunosuppression therapy, with no evidence of graft-versus-host disease.
* Eastern Cooperative Oncology Group performance status 0-2.
* Adequate hematological function
* Adequate organ function
* Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception for 30 days prior to the first dose of investigational product, and must agree to continue using such precautions for 180 days after the final dose of investigational product.
* Nonsterilized males who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception from Day 1through 90 days after receipt of the final dose of investigational product.

Key exclusion criteria:

* Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy for treatment of cancer.
* Receipt of any experimental therapy, mAb, cancer vaccine, chemotherapy or small molecule within 28 days prior to Cycle 1 Day 1 or 5 half-lives of that therapy, whichever is shorter.
* Previous therapy directed against cluster of differentiation 19 (CD19)
* Prior exposure to immunotherapy such as but not limited to other anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), anti-PD 1, or anti-PD-L1 antibodies excluding cancer vaccines.
* Vaccination with a live virus within 28 days prior to receiving the first dose of study drug
* History of other invasive malignancy within 2 years except for cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has been surgically cured.
* Evidence of significant active infection requiring antimicrobial, antifungal, antiparasitic, or antiviral therapy or for which other supportive care is given unless the subject is clinically stable.
* Human immunodeficiency virus (HIV) positive serology or acquired immunodeficiency syndrome (AIDS).
* Active hepatitis B
* Ongoing \>= Grade 2 toxicities from previous cancer therapies or any unresolved \> Grade 1 immune-related adverse event (irAE) event unless specifically allowed in the inclusion/exclusion criteria.
* No immunosuppressive therapy within 14 days of Cycle 1 Day 1 of MEDI0680 (AMP-514) dosing.
* Active or prior documented autoimmune or inflammatory disease except vitiligo.
* History of primary immunodeficiency.
* Major surgical procedures (as defined by the principal investigator) within 28 days of Cycle 1 Day 1 or still recovering from prior surgery.
* History of tuberculosis, including those who may have completed prophylactic isoniazid (INH) therapy.
* Documented current central nervous system (CNS) involvement, leptomeningeal disease, or spinal cord compression.
* Pregnancy or lactation.
* Clinically significant abnormality on electrocardiogram (ECG).
* Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, current pneumonitis, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs from MEDI-551 or MEDI0680 (AMP-514), or compromise the ability of the subject to give written informed consent.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of MEDI-551
timeFrame: Day 1 to Day 28 of Cycle 1 (28-day cycle)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities
timeFrame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Vital Signs, Physical Findings Abnormalities
timeFrame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)
measure: Number of Participants With Best Overall Response
timeFrame: Day 1 to Day 28 of Cycle 13 (28-day cycle)
Secondary outcomes:
measure: Mean Peak and Trough Concentrations of MEDI551
timeFrame: End of Infusion (EOI) of Cycle 1 Day 1; Pre-dose and EOI of C1D8, C2D1, C3D1 and C4D1
measure: Mean Peak and Trough Concentrations of MEDI0680
timeFrame: EOI of Cycle 1 Day 2; Pre-dose and EOI of C1D15, C2D1, C3D1 and C4D1
measure: Terminal Half-Life (t1/2) of MEDI551
timeFrame: EOI of Cycle 1 Day 1; Pre-dose and EOI of C1D8, C2D1, C3D1 and C4D1
measure: Terminal Half-Life (t1/2) of MEDI0680
timeFrame: EOI of Cycle 1 Day 2; Pre-dose and EOI of C1D15, C2D1, C3D1 and C4D1
measure: Number of Participants With Positive Anti-Drug Antibodies (ADA) for MEDI-551 and MEDI0680
timeFrame: 30 min prior to infusion of MEDI-551 on Day 1 of Cycles 1, 2, 6, 9, and 12 and up to 90-days after last dose of study drug (up to approximately 2 years)
measure: Duration of Complete Response
timeFrame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)
measure: Number of Participants With Disease Control
timeFrame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)
measure: Duration of Disease Control
timeFrame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)
measure: Progression-free Survival (PFS)
timeFrame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)
measure: Overall Survival (OS)
timeFrame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)
measure: Time to Response (TTR)
timeFrame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Bronx
country: United States
facility: Research Site
state: New York
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
Study officials:
affiliation: MedImmune LLC
name: MedImmune LLC
role: STUDY_DIRECTOR
References: