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A Clinical Study Using MEDI-551 in Adult Subjects With Relapsed or Refractory Advanced B-Cell Malignancies

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by MedImmune LLC
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT00983619
First received: September 22, 2009
Last updated: May 14, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to determine the maximum tolerated dose of this drug (MEDI-551) in subjects with advanced B-cell malignancies. Expansion to occur at maximum tolerated dose (MTD), or if not reached, at optimal biologic dose (OBD).


Condition Intervention Phase
B-cell Malignancies
Drug: MEDI-551
Drug: Rituximab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1, Dose-escalation Study of MEDI-551, a Humanized Monoclonal Antibody Directed Against CD19, in Adult Subjects With Relapsed or Refractory Advanced B-Cell Malignancies

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • To evaluate the MTD or highest protocol defined dose of MEDI-551 in subjects with relapsed or refractory advanced B-cell malignancies and to determine the preliminary safety profile in these populations. [ Time Frame: Study Day 28 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate the efficacy of MEDI-551 in subjects with advanced B-cell malignancies, and to characterize the PK and effect on circulating lymphocyte populations and Ig levels, and the immunogenicity of MEDI-551. [ Time Frame: 30 days after last dose of study drug ] [ Designated as safety issue: No ]

Estimated Enrollment: 213
Study Start Date: April 2010
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Escalation: Cohort 1 (FL/MM)
Subjects are dosed with Dose level 1 of active drug.
Drug: MEDI-551
A humanized Immunoglobulin G (IgG)1 kappa monoclonal antibody (MAb) directed against human CD19.
Experimental: Dose Escalation: Cohort 2 (FL/MM)
Subjects will be dosed with Dose level 2 of active drug.
Drug: MEDI-551
A humanized Immunoglobulin G (IgG)1 kappa monoclonal antibody (MAb) directed against human CD19.
Experimental: Dose Escalation: Cohort 3 (FL/MM/CLL/DLBCL)
Subjects will be dosed with dose level 3 of active drug.
Drug: MEDI-551
A humanized Immunoglobulin G (IgG)1 kappa monoclonal antibody (MAb) directed against human CD19.
Experimental: Dose Escalation: Cohort 4 (CLL/DLBCL/FL)
Subjects will be dosed with dose level 4 of active drug.
Drug: MEDI-551
A humanized Immunoglobulin G (IgG)1 kappa monoclonal antibody (MAb) directed against human CD19.
Experimental: Dose Escalation: Cohort 5 (FL/MM/CLL/DLBCL)
Subjects will be dosed with dose level 5 of active drug.
Drug: MEDI-551
A humanized Immunoglobulin G (IgG)1 kappa monoclonal antibody (MAb) directed against human CD19.
Experimental: Dose Escalation: Cohort 6 (FL/MM/CLL/DLBCL)
Subjects will be dosed with dose level 6 of active drug.
Drug: MEDI-551
A humanized Immunoglobulin G (IgG)1 kappa monoclonal antibody (MAb) directed against human CD19.
Experimental: Dose Expansion: Cohort 7 (FL)
Subjects will be dosed with MTD or OBD determined for FL.
Drug: MEDI-551
A humanized Immunoglobulin G (IgG)1 kappa monoclonal antibody (MAb) directed against human CD19.
Experimental: Dose Expansion: Cohort 8 (CLL)
Subjects will be dosed with MTD or OBD determined for CLL.
Drug: MEDI-551
A humanized Immunoglobulin G (IgG)1 kappa monoclonal antibody (MAb) directed against human CD19.
Experimental: Dose Expansion: Cohort 9 (DLBCL)
Subjects will be dosed with MTD or OBD determined for DLBCL.
Drug: MEDI-551
A humanized Immunoglobulin G (IgG)1 kappa monoclonal antibody (MAb) directed against human CD19.
Experimental: Dose Escalation: Cohort 10 (CLL)
Subjects will be dosed with Dose Level 1 of active drug for CLL dose escalation.
Drug: MEDI-551
A humanized Immunoglobulin G (IgG)1 kappa monoclonal antibody (MAb) directed against human CD19.
Experimental: Dose Escalation: Cohort 11 (CLL)
Subjects will be dosed with Dose Level 2 of active drug for CLL dose escalation.
Drug: MEDI-551
A humanized Immunoglobulin G (IgG)1 kappa monoclonal antibody (MAb) directed against human CD19.
Experimental: Dose Expansion: Cohort 12 (CLL)
Subjects will be dosed with Dose Level 3 of active drug for CLL dose escalation.
Drug: MEDI-551
A humanized Immunoglobulin G (IgG)1 kappa monoclonal antibody (MAb) directed against human CD19.
Experimental: Dose Expansion: Cohort 13 (CLL)
Subjects will be dosed with Dose Level 4 of active drug for CLL dose escalation.
Drug: MEDI-551
A humanized Immunoglobulin G (IgG)1 kappa monoclonal antibody (MAb) directed against human CD19.
Experimental: Dose Expansion: Cohort 14 (CLL)
Subjects will be dosed based on the MTD identified in the dose escalation CLL phase (Cohorts 10-13)
Drug: MEDI-551
A humanized Immunoglobulin G (IgG)1 kappa monoclonal antibody (MAb) directed against human CD19.
Experimental: Dose Escalation: Cohort 15 (Agressive Lymphoma)
Subjects are dosed with dose level 1 of active drug and 375 mg/m2 of rituximab.
Drug: MEDI-551
A humanized Immunoglobulin G (IgG)1 kappa monoclonal antibody (MAb) directed against human CD19.
Drug: Rituximab
Ritimab and MEDI-551
Experimental: Dose Escalation: Cohort 16 (Agressive Lymphoma)
Subjects are dosed with dose level 2 of active drug and 375 mg/m2 of rituximab.
Drug: MEDI-551
A humanized Immunoglobulin G (IgG)1 kappa monoclonal antibody (MAb) directed against human CD19.
Drug: Rituximab
Ritimab and MEDI-551
Experimental: Dose Expansion: Cohort 17 (Agressive Lymphoma)
Subjects are dosed with MTD identified in the dose escalation phase (Cohorts 15-16) and 375 mg/m2 of rituximab.
Drug: MEDI-551
A humanized Immunoglobulin G (IgG)1 kappa monoclonal antibody (MAb) directed against human CD19.
Drug: Rituximab
Ritimab and MEDI-551
Experimental: CD20 Refractory Agressive Lymphoma (Cohort 18)
Subject will be dosed based on MTD identified in dose escalation (Cohorts 1-6)
Drug: MEDI-551
A humanized Immunoglobulin G (IgG)1 kappa monoclonal antibody (MAb) directed against human CD19.

Detailed Description:

To determine the maximum tolerated dose (MTD) or optimal biologic dose (OBD) of MEDI-551 in subjects with relapsed or refractory advanced B-cell malignancies.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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. 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 C: Histologically confirmed aggressive B-cell DLBCL, including FL transforming to DLBCL, transformed indolent lymphoma, MCL, or Grade 3b FL, according to the World Health Organization (WHO)/American Joint Committee on Cancer (AJCC) criteria 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 WHO/AJCC criteria
  4. Optional: Willing to provide a fresh tumor sample if a sufficient quantity of archival tumor sample is not available (Arms B, C, and D). See Section 5.3.9 for tumor sample details.
  5. Evaluable/measurable disease

    Non-CLL B-cell malignancies (Arms A, C, 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 Arms C and 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 C: 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
    • 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 hematologic function

    Arm A (except for CLL subjects with significant BM involvement by biopsy) must meet the following criteria:

    • Hemoglobin ≥ 9 g/dL, (≥ 8 g/dL for subjects who are transfusion dependent)
    • Absolute neutrophil count ≥ 1500/mm3
    • Platelet count ≥ 75,000/mm3

    Arms B, C, and D must meet the following criteria:

    • Hemoglobin ≥ 8 g/dL
    • Absolute neutrophil count ≥ 1000/mm3
    • Platelet count ≥ 75,000/mm3
    • In the event of significant BM involvement, the above hematologic criteria will not be required for enrollment eligibility
  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 for subjects with documented Gilbert's disease, ≤ 2.5 × ULN;
    • Serum creatinine ≤ 1.5 mg/dL or a calculated creatinine clearance of ≥ 60 mL/min as determined by the Cockcroft-Gault equation
  12. Female subjects of childbearing potential who are sexually active with a nonsterilized male partner must use highly effective contraception from screening and must agree to continue using such precautions for at least 180 days after the last dose of investigational product. Depending on the investigational product received, this period may be longer. Cessation of birth control after this point should be discussed with a responsible physician

    • Females of childbearing potential are defined as those who are not surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or those who are postmenopausal (defined as 12 months with no menses without an alternative medical cause or follicle-stimulating hormone/luteinizing hormone levels consistent with a menopausal state)
    • A highly effective method of contraception is defined as one that results in a low failure rate (ie, less than 1% per year) when used consistently and correctly. Acceptable methods of contraception are described in Table 4.2.1-1. Sustained abstinence is an acceptable practice; however, periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception
  13. Non-sterilized males who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception (Table 4.2.1-1) from at least Day 1 through 90 days after the last dose of investigational product
  14. Negative serum beta human chorionic gonadotropin (βhCG) test (for women of childbearing potential only)
  15. Females or female partners not of childbearing potential must have been surgically sterilized or postmenopausal (as defined above in inclusion criterion #12). Sterilized males must be at least 1 year post vasectomy

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) 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 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. This does not include required steroid prophylaxis prior to the first infusion 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 involved with the conduct of the study, or immediate family members of such individuals. These subjects may be treated at another site participating in the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00983619

Contacts
Contact: Isoke Sawyer ClinicalTrialEnquiries@Medimmune.com

Locations
United States, Alabama
Research Site Recruiting
Birmingham, Alabama, United States
United States, California
Research Site Recruiting
La Jolla, California, United States
United States, District of Columbia
Research Site Recruiting
Washington, District of Columbia, United States
United States, Florida
Research Site Active, not recruiting
Tampa, Florida, United States
United States, Illinois
Research Site Completed
Chicago, Illinois, United States
United States, Texas
Research Site Active, not recruiting
Houston, Texas, United States
United States, West Virginia
Research Site Recruiting
Morgantown, West Virginia, United States
Belgium
Research Site Completed
Gent, Belgium
Research Site Completed
Leuven, Belgium
Research Site Active, not recruiting
Yvoir, Belgium
Canada, Quebec
Research Site Completed
Montreal, Quebec, Canada
France
Research Site Recruiting
Pierre Bénite, France
Italy
Research Site Active, not recruiting
Ferrara, Italy
Research Site Active, not recruiting
Modena, Italy
Research Site Not yet recruiting
Pesaro, Italy
Research Site Not yet recruiting
Rozzano, Italy
Spain
Research Site Active, not recruiting
Madrid, Spain
Research Site Recruiting
Salamanca, Spain
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: Trishna Goswami, M.D. MedImmune LLC
  More Information

Additional Information:
No publications provided

Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT00983619     History of Changes
Other Study ID Numbers: MI-CP204
Study First Received: September 22, 2009
Last Updated: May 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by MedImmune LLC:
Cancer

Additional relevant MeSH terms:
Neoplasms
Antibodies, Monoclonal
Rituximab
Antineoplastic Agents
Antirheumatic Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014