E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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)) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008976 |
E.1.2 | Term | Chronic lymphocytic leukemia |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012818 |
E.1.2 | Term | Diffuse large B-cell lymphoma |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067070 |
E.1.2 | Term | Follicular B-cell non-Hodgkin's lymphoma |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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.
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E.2.2 | Secondary objectives of the trial |
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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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). Sterilized males must be at least 1-year post vasectomy; 13) For the expansion phase only, for subjects with DLBCL or FL only, disease evaluable by the International Working Group criteria. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Maximum Tolerated Dose / Optimal Biological Dose and Safety |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |