A Study of MEDI-551 in Adult Subjects With Relapsed or Refractory Advanced B-Cell Malignancies
- Conditions
- Relapsed or refractory advanced B-cell malignancies: chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), B-cell non-Hodgkin’s lymphoma (NHL) (subtypes: follicular lymphoma (FL), diffuse large B-cell lymphoma(DLBCL), mantle cell lymphoma, and anti-CD20-refractory aggressive lymphomas)MedDRA version: 20.1 Level: LLT Classification code 10008976 Term: Chronic lymphocytic leukemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: LLT Classification code 10067070 Term: Follicular B-cell non-Hodgkin's lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: PT Classification code 10012818 Term: Diffuse large B-cell lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2009-016378-34-BE
- Lead Sponsor
- MedImmune LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 193
1)Men or women at least 18 years of age or older at time of study entry
2)Written informed consent obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations
3)Diagnosis
?Arm A: CLL (including SLL), DLBCL, or FL; SLL, DLBCL, and FL must be histologically confirmed
?Arm B: Histologically confirmed SLL or previous confirmation of B-cell CLL with a characteristic immunophenotype by flow cytometry
?Arm D: Histologically confirmed anti-CD20-refractory (defined as any subject with less than a PR to any prior anti-CD20-based therapy or progression within 6 months after completing therapy with any anti-CD20-based regimen, including maintenance rituximab) aggressive B-cell DLBCL, including FL transforming to DLBCL, transformed indolent lymphoma, MCL, or Grade 3b FL, according to the World Health Organization/American Joint Committee on Cancer criteria
4)Optional: Willing to provide a fresh tumor sample if a sufficient quantity of archival tumor sample is not available (Arms B and D)
5)Evaluable/measurable disease
?Non-CLL B-cell malignancies (Arms A and D):
?Histologically confirmed B-cell NHL (FL or DLBCL), transformed indolent lymphoma, and MCL: Measurable disease defined as = 1 lesion = 20 mm in one dimension or =15 mm in 2 dimensions as measured by conventional or high-resolution (spiral) computed tomography (CT). For Arm D: disease evaluable by the International Working Group criteria (Cheson et al, 2007)
?Baseline PET or PET/CT scans must show positive lesions compatible with CT-defined anatomical tumor sites (only applicable for FL, DLBCL, MCL, transformed indolent lymphoma, and FL transforming to DLBCL)
?CLL (Arms A and B):
?Confirmed B-cell CLL/SLL with a characteristic immunophenotype by flow cytometry, and symptomatic disease requiring treatment
?CT scans showing involvement of = 1clearly demarcated lesions measuring = 1.5 cm
6)Prior therapy
?Arm A:
?Histologically confirmed B-cell NHL (FL or DLBCL): Relapsed from or refractory to = 1 prior regimen containing rituximab, either alone or in combination, and not be a candidate for hematopoietic SCT or BM transplant
?B-cell CLL: Relapsed from or refractory to = 2 prior lines of treatment, = 1 of which must have contained rituximab
?Arm B: Relapsed from or refractory to = 2 prior chemotherapy regimens with = 1 regimen containing rituximab
?Arm D: Refractory to = 1 regimen containing any anti-CD20-based therapy, including salvage regimens and maintenance rituximab. Refractory subjects are defined as any subject with less than a PR to any prior anti-CD20-based therapies or progressed within 6 months after completing therapy with any anti-CD20-based regimens, including maintenance rituximab. These subjects must not be eligible for hematopoietic SCT or BM transplant
7)Prior radiation therapy is allowed provided exposure does not exceed an area of 25% of marrow space and occurred = 6 weeks prior to the first dose of MEDI-551 (Arm A only)
8)Karnofsky Performance Status = 70
9)Life expectancy of = 12 weeks
10)Adequate hem
1)Any available standard line of therapy known to be life-prolonging or life-saving
2)Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy for treatment of cancer
3)History of allergy or reaction to any component of the MEDI-551 formulation
4)Receipt of any chemotherapy or small molecule targeted therapy (such as imatinib or other tyrosine kinase inhibitors, and including any experimental therapies) or radiation therapy within 28 days or 5 half-lives, whichever is shorter, prior to the first dose of MEDI-551
5)Receipt of any biological or immunological-based therapies (including experimental therapies) for leukemia, lymphoma, or myeloma (including, but not limited to, MAb therapy such as rituximab, or cancer vaccine therapies) within 28 days or 5 half-lives, whichever is shorter, prior to the first dose of MEDI-551
6)Previous therapy directed against CD19, such as MAbs or MAb conjugates
7)Live or attenuated vaccines (other than experimental cancer vaccine therapy) within 28 days prior to receiving the first dose of MEDI-551
8)Evidence of significant active infection requiring antimicrobial, antifungal, antiparasitic, or antiviral therapy or for which other supportive care is given
9)Autologous SCT within 12 weeks prior to study entry (Arms A and D only)
10)Prior allogeneic SCT or organ transplant (Arms A and D only)
11)Human immunodeficiency virus (HIV) positive serology or AIDS
12)Active hepatitis B as defined by seropositivity for hepatitis B surface antigen (HBsAg) or positive hepatitis B core antibody. Subjects with hepatitis C antibody will be eligible provided that they do not have elevated liver transaminases
13)Ongoing = Grade 2 toxicities from previous cancer therapies unless specifically allowed in the Inclusion/Exclusion criteria. Use of immunosuppressive medication other than steroids within 28 days before the first dose of MEDI-551
14)Use of systemic steroids within 7 days before the first dose of MEDI-551 (inhaled and topical corticosteroids are permitted). Subjects may take replacement doses of steroids (defined as = 30 mg/day hydrocortisone or the equivalent) if on a stable dose for at least 2 weeks prior to the first dose of MEDI-551
15)Documented current central nervous system involvement by leukemia or lymphoma
16)Pregnancy or lactation
17)Previous medical history, or evidence, of an intercurrent illness that at the discretion of the principal investigator may compromise the safety of the subject in the study
18)Clinically significant abnormality on electrocardiogram (ECG). The corrected QT interval (QTc, Fridericia) must be < 470 milliseconds for men and < 490 milliseconds for women (Must be confirmed by at least 2 additional 12-lead ECGs at least 2 minutes apart such that average manually over-read QTcF based on 3 ECGs exceeds stated thresholds)
19)Any physical, social, or psychiatric condition that would prevent effective cooperation or participation in the study
20)Concurrent enrollment in another clinical study, unless in a follow-up period or it is an observational study
21)Employees of the clinical study site who are directly
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method