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Safety Study of CAT-8015 to Treat Advanced B-cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (NHL or CLL)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT01030536
First received: December 9, 2009
Last updated: May 21, 2013
Last verified: May 2013
  Purpose

The primary objectives of this study are to determine the maximum tolerated dose (MTD) or optimal biologic dose (OBD) and safety profile of CAT-8015 in subjects with relapsed or refractory advanced B-cell NHL (DLBCL, FL, MCL) or CLL.


Condition Intervention Phase
Non-Hodgkin Lymphoma
Chronic Lymphocytic Leukemia
Drug: CAT-8015 Immunotoxin (Moxetumomab Pasudotox)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of CAT-8015 in Adult Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • The primary objectives of this study are to determine the MTD or OBD and safety profile of CAT-8015 in subjects with relapsed or refractory advanced B-cell NHL (DLBCL, FL, MCL) or CLL; including SLL. [ Time Frame: 29 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To describe the preliminary efficacy profile of CAT-8015 in subjects with relapsed or refractory advanced B-cell NHL (DLBCL, FL, MCL) or CLL;including SLL. The pharmacokinetics of CAT-8015; and investigate other laboratory measures and predictors of VLS. [ Time Frame: 29 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 87
Study Start Date: March 2010
Study Completion Date: April 2013
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Escalation Arm A
CLL, DLBCL, MCL
Drug: CAT-8015 Immunotoxin (Moxetumomab Pasudotox)
2-mL sized vials of CAT-8015 at a target concentration of 1.0 mg per vial
Experimental: Escalation Arm B
FL
Drug: CAT-8015 Immunotoxin (Moxetumomab Pasudotox)
2-mL sized vials of CAT-8015 at a target concentration of 1.0 mg per vial
Experimental: Expansion Arm 1
CLL
Drug: CAT-8015 Immunotoxin (Moxetumomab Pasudotox)
2-mL sized vials of CAT-8015 at a target concentration of 1.0 mg per vial
Experimental: Expansion Arm 2
DLBCL
Drug: CAT-8015 Immunotoxin (Moxetumomab Pasudotox)
2-mL sized vials of CAT-8015 at a target concentration of 1.0 mg per vial
Experimental: Expansion Arm 3
MCL
Drug: CAT-8015 Immunotoxin (Moxetumomab Pasudotox)
2-mL sized vials of CAT-8015 at a target concentration of 1.0 mg per vial
Experimental: Expansion Arm 4
FL
Drug: CAT-8015 Immunotoxin (Moxetumomab Pasudotox)
2-mL sized vials of CAT-8015 at a target concentration of 1.0 mg per vial

Detailed Description:

To determine the maximum tolerated dose (MTD) or optimal biologic dose (OBD) of CAT-8015 in subjects with relapsed or refractory advanced B-cell NHL (DLBCL, FL, MCL) or CLL.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Subjects must be at least 18 years of age or older
  • Written informed consent and HIPAA authorization
  • Subjects must have histologically-confirmed B-cell CLL, including SLL, DLBCL, MCL, or FL.
  • B-cell NHL (DLBCL, FL, MCL):

    • Have previous confirmation of B-cell NHL
    • Subjects with DLBCL or MCL, must have relapsed or refractory disease after at least one prior regimen containing rituximab, either alone or in combination, and be ineligible for any available standard line of therapy known to be life-prolonging or life-saving.
    • Subjects with FL, must have relapsed or refractory disease after at least two prior regimens, one of which included rituximab, either alone or in combination, and be ineligible for any available standard line of therapy known to be life-prolonging or life-saving.
    • 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 a candidate for a hematopoietic stem cell (HSC) or bone marrow (BM) transplant
  • B-cell CLL:

    • Have previous confirmation of B-cell CLL with a characteristic immunophenotype by flow cytometry
    • Have relapsed or refractory disease after at least 2 prior lines of treatment, at least 1 of which must have contained rituximab and be ineligible for any available standard line of therapy known to be life-prolonging or life-saving
    • Not be a candidate for an HSC or BM transplant
    • Have symptomatic disease that requires treatment
  • Karnofsky Performance Status ≥ 70
  • Life expectancy of ≥ 12 weeks
  • Toxicities from previous cancer therapies must have recovered to Grade < 2.
  • 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)
  • Adequate organ function defined as follows:

    • AST and ALT ≤ 2 × institutional ULN, except in the case of liver involvement ≤ 5 × ULN
    • Bilirubin ≤ 1.5 × ULN, except in the case of subjects with documented Gilbert's disease ≤ 2.5 × ULN
    • Creatinine clearance ≥ 50 mL/min as determined by the Cockcroft-Gault equation or by 24-hour urine collection for determination of creatinine clearance
  • PT-INR/ PTT ≤ 1.5 × ULN, or for patients on anticoagulation therapy, status within therapeutic range
  • Women of non-child-bearing potential or using effective contraception
  • Male subjects with partners of child-bearing potential must be surgically sterile or use a contraceptive method
  • For the expansion phase only, subjects with DLBCL, FL, and MCL only, disease must be evaluable by the International Working Group criteria (Cheson et al, 2007).

Exclusion Criteria

Any of the following excludes the subject from participation in the study:

  • Any available standard line of therapy known to be life-prolonging or life-saving
  • Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic, or hormonal therapy for treatment of cancer
  • For CLL patients only,rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy
  • History of allergy or reaction to any component of the CAT-8015 formulation
  • Receipt of any chemotherapy or small molecule targeted therapy regimens within 6 weeks
  • Receipt of any biological- or immunological-based therapies for leukemia or lymphoma within 6 weeks
  • Prior radiation therapy will not be excluded, providing the volume of bone marrow treated is less than 25%.
  • Any history of prior pseudomonas-exotoxin (PE) immunotoxin administration including CAT-8015, CAT-3888, or LMB-2 (anti-CD25 immunotoxin)
  • History of other invasive malignancy within 5 years, with some exceptions
  • Evidence of significant active infection requiring antimicrobial, antifungal, antiparasitic or antiviral therapy or for which other supportive care is given
  • Autologous stem cell transplantation within 6 months prior to study entry
  • Allogenic stem cell transplantation or any other organ transplant
  • HIV-positive or AIDS
  • Hepatitis B or hepatitis C infection as defined by seropositive for hepatitis B (HBsAg) or hepatitis C and elevated liver transaminases
  • Use of immunosuppressive medication other than steroids within 7 days
  • Use of systemic steroids within 7 days before the first dose of CAT-8015 (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 CAT-8015.
  • Documented current central nervous system involvement by leukemia or lymphoma
  • Pregnancy or lactation
  • Other severe, concurrent diseases
  • Concurrent enrollment in another clinical 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: NCT01030536

Locations
United States, California
Research Site
Los Angeles, California, United States
United States, Indiana
Research Site
Indianapolis, Indiana, United States
United States, Maryland
Research Site
Bethesda, Maryland, United States, 20892
United States, Nevada
Research Site
Las Vegas, Nevada, United States
United States, South Carolina
Research Site
Charleston, South Carolina, United States
United States, Tennessee
Research Site
Nashville, Tennessee, United States
United States, Texas
Research Site
Temple, Texas, United States
Germany
Research Site
Regensburg, Bayern, Germany, 93053
Poland
Research Site
Łódź, Poland
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: Ramy Ibrahim, M.D. MedImmune LLC
  More Information

Additional Information:
No publications provided

Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT01030536     History of Changes
Obsolete Identifiers: NCT01086644
Other Study ID Numbers: MI-CP218
Study First Received: December 9, 2009
Last Updated: May 21, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by MedImmune LLC:
NHL
CLL

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on November 20, 2014