Relasped or refractory advanced B-cell malignancies: chronic lymphocytic leukemia (CLL), multiple myeloma (MM), B-cell non-Hodgkin’s lymphoma (NHL) (subtypes: follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL)) MedDRA version: 12.1 Level: LLT Classification code 10008976 Term: Chronic lymphocytic leukemia MedDRA version: 12.1 Level: LLT Classification code 10012818 Term: Diffuse large B-cell lymphoma MedDRA version: 12.1 Level: LLT Classification code 10028228 Term: Multipl
Conditions
Interventions
Product Name: MEDI-551
Product Code: MEDI-551
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: NA
CAS Number: NA
Current Sponsor code: NA
Other descriptive name: 16C4-aFuc
Concentration
Sponsors
MedImmune, LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Men or women at least 18 years of age or older at time of study entry; 2) Written informed consent and HIPAA authorization (applies to covered entities in the USA only) obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations; 3) Histologically confirmed CLL (including SLL), DLBCL, FL, or MM; 4) Subjects with histologically-confirmed B-cell NHL (FL or DLBCL) must: •Be relapsed or refractory after at least one prior regimen containing rituximab, either alone or in combination; •Have measurable disease (at least one lesion = 20 mm in one dimension or =15 mm in two dimensions as measured by conventional or high resolution [spiral] computed tomography (CT); •Not be candidates for hematopoietic stem cell (HSC) or bone marrow (BM) transplant; 5) For B-cell CLL subjects, the following criteria are required for eligibility: •Previous confirmation of B-cell CLL with a characteristic immunophenotype by flow cytometry; •Be relapsed or refractory after at least 2 prior lines of treatment, at least one of which must have contained rituximab and not be a candidate for hematopoietic stem cell (HSC) or bone marrow (BM) transplant; •Have symptomatic disease that requires treatment; 6) For subjects with MM, the following criteria are required: •Be relapsed or refractory after at least one prior line of therapy; •Not be a candidate for HSC or BM transplant; •Indication for active treatment as follows: •Presence of an M-component in serum and/or urine plus clonal plasma cells in the bone marrow and/or documented clonal plasmacytoma; •Plus one or more of the following: •Calcium elevation (> 11.5 mg/dL); •Renal insufficiency (creatinine > 2.0 mg/dL); •Anemia (hemoglobin < 10 g/dL); •Bone disease (lytic bone lesions by X-ray or CT scan or osteopenia considered secondary to MM); 7) Karnofsky Performance Status = 70; 8) Life expectancy of = 12 weeks; 9) Prior radiation therapy is allowed provided exposure does not exceed an area of 25% of marrow space; 10) Adequate hematological function defined as: •Hemoglobin = 9 g/dL; •Absolute neutrophil count = 1500/mm3; •Platelet count = 75,000/mm3 (except for CLL subjects with evidence of bone marrow disease, who must have a platelet count = 50,000/mm3);; 11) Adequate organ function defined as follows: •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2 × institutional upper limit of normal (ULN); •Bilirubin = 1.5 × ULN except in the case of subjects with documented Gilbert’s disease, = 2.5 × ULN; •Serum creatinine < ULN or for MM only, < 5 × ULN; 12) Female subjects of childbearing potential who are sexually active with a non-sterilized male partner must use adequate contraception from screening through 90 days after the last dose of MEDI-551. An acceptable method of contraception is defined as one that has no higher than a 1% failure rat. Sustained abstinence is an acceptable practice; however, periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Non-sterilized males who are sexually active with a female of child-bearing potential must use adequate contraception from screening through 90 days after the last dose of MEDI-551; •Females or female partners not of childbearing potential must have been surgically sterilized (eg, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or postmenopausal (defined as at least 1 year since last regular menses). S
Exclusion criteria
Exclusion criteria: 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) regimens within 6 weeks 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, monoclonal antibody therapy such as rituximab, or cancer vaccine therapies) within 6 weeks prior to the first dose of MEDI-551 (This time period is approximately 2 terminal elimination half-lives of rituximab, and represents a reasonable time for subjects with progressing disease to wait for therapy). 6) Previous therapy directed against CD19, such as monoclonal antibodies or monoclonal antibody conjugates; 7) Vaccination (other than experimental cancer vaccine therapy) within 28 days prio to receiving the first dose of MEDI-551; 8) History of other invasive malignancy within 5 years except for cervical carcinoma in situ (CIS), non-melanomatous carcinoma of the skin or ductal carcinoma in situ (DCIS) of the breast that have been surgically cured; 9) Evidence of significant active infection requiring antimicrobial, antifungal, antiparasitic, or antiviral therapy or for which other supportive care is given; 10) Autologous stem cell transplantation within 12 weeks prior to study entry; 11) Allogeneic stem cell transplantation or any other organ transplant; 12) HIV positive serology or AIDS; 13) Active hepatitis B or C infection as defined by seropositivity for hepatitis B (HBsAg) or hepatitis C antibody, and elevated liver transaminases; 14) Ongoing = Grade 2 toxicities from previous cancer therapies unless specifically allowed in the Inclusion/Exclusion criteria. For subjects with MM, serum calcium must be < Grade 4 (< 13.5 mg/dL) and serum creatinine must be < 5 × ULN; 15) Use of immunosuppressive medication other than steroids within 28 days before the first dose of MEDI-551; 16) 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; 17) Documented current central nervous system involvement by leukemia or lymphoma; 18) Pregnancy or lactation; 19) 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; 20) Clinically significant abnormality on ECG. The QTc (Fridericia) for men must be < 470 msec, and for women < 490 msec; 21) Any physical, social, or psychiatric condition that would prevent effective cooperation or participation in the study; 22) Concurrent enrollment in another clinical study; 23) Employees of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to determine the MTD or OBD of MEDI-551 in subjects with relapsed or refractory advanced B-cell malignancies and to determine the preliminary safety profile of MEDI-551. ;Secondary Objective: 1 To determine the preliminary efficacy profile of MEDI-551 in subjects with the following advanced B-cell malignancies: •CLL •DLBCL •FL •MM 2 To determine the pharmacokinetics (PK) of MEDI-551 in subjects with advanced B cell malignancies. 3 To determine the effect of treatment with MEDI-551 on circulating lymphocyte populations and immunoglobulin levels, including time to recovery after treatment. 4 To determine the immunogenicity of MEDI-551 in these patient populations. ;Primary end point(s): Maximum Tolerated Dose / Optimal Biological Dose and Safety | — |
Countries
Belgium, France
Outcome results
None listed