Clinical trial NCT01030536: Safety Study of CAT-8015 to Treat Advanced B-cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (NHL or CLL)
Official title: A Phase 1/2 Study of CAT-8015 in Adult Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Non-Hodgkin Lymphoma
Chronic Lymphocytic Leukemia
Keywords: NHL
CLL
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2009-12-11
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 participants with relapsed or refractory advanced B-cell NHL (diffuse large B-cell lymphoma \[DLBCL\], follicular lymphoma \[FL\], mantle cell lymphoma \[MCL\]) or CLL.

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

Eligibility criteria: Inclusion Criteria:

* Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization
* Participants must have histologically confirmed B-cell CLL, including small lymphocytic lymphoma (SLL), DLBCL, MCL, or FL
* B-cell NHL: a) Have previous confirmation of B-cell NHL b) Participants 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 c) Participants 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 d) Have measurable disease (at least one lesion greater than or equal to (≥) 20 millimeter (mm) in one dimension or ≥ 15 mm in two dimensions as measured by conventional or high resolution \[spiral\] computed tomography e) Not be a candidate for a hematopoietic stem cell (HSC) or bone marrow transplant
* B-cell CLL: a) Have previous confirmation of B-cell CLL with a characteristic immunophenotype by flow cytometry b) 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 c) Not be a candidate for an HSC or BM transplant d) 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 less than (\<) 2
* Adequate hematological function defined as: a) Hemoglobin ≥ 9 g/dL b) Absolute neutrophil count ≥ 1500/mm\^3 c) Platelet count ≥ 75,000/mm\^3
* Prothrombin time-International Normalized Ratio/Partial thromboplastin time less than or equal to (≤) 1.5 × upper limit of normal (ULN), or for participants on anticoagulation therapy, status within therapeutic range
* Women of non-child-bearing potential or using effective contraception
* Male participants with partners of child-bearing potential must be surgically sterile or use a contraceptive method

Exclusion Criteria:

* 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 participants 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
* Receipt of any chemotherapy or small molecule targeted therapy or 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 percent
* Any history of prior pseudomonas-exotoxin immunotoxin administration including CAT-8015, CAT-3888, or LMB-2
* 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). Participants 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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: Day 1 to end of Cycle 1 (approximately 28 days)
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Day 1 to end of Cycle 1 (approximately 28 days)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: From Screening (Day -28) to Post Therapy Day 30
measure: Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From Screening (Day -28) to Post Therapy Day 30
measure: Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From Screening (Day -28) to Post Therapy Day 30
measure: Number of Participants With Electrocardiogram (ECG) Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From Screening (Day -28) to Post Therapy Day 30
Secondary outcomes:
measure: Percentage of Participants With Complete Response (CR)
timeFrame: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
measure: Duration of Complete Response
timeFrame: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
measure: Percentage of Participants With Partial Response (PR)
timeFrame: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
measure: Percentage of Participants With Objective Response (OR)
timeFrame: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
measure: Time to Response (TTR)
timeFrame: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
measure: Duration of Objective Response (DOR)
timeFrame: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
measure: Duration of Stable Disease (SD)
timeFrame: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
measure: Maximum Plasma Concentration (Cmax) of Moxetumomab Pasudotox
timeFrame: Pre-dose and End of infusion on Day 1, 3 and 5 of each cycle; 1, 3 and 6 hour after the end of infusion on Day 1 of each cycle
measure: Area Under Concentration-Time Curve From Dosing Extrapolated to Infinity (AUCinf) of Moxetumomab Pasudotox
timeFrame: Pre-dose and End of infusion on Day 1, 3 and 5 of each cycle; 1, 3 and 6 hour after the end of infusion on Day 1 of each cycle
measure: Clearance (CL) of Moxetumomab Pasudotox
timeFrame: Pre-dose and End of infusion on Day 1, 3 and 5 of each cycle; 1, 3 and 6 hour after the end of infusion on Day 1 of each cycle
measure: Elimination Half Life (t1/2) of Moxetumomab Pasudotox
timeFrame: Pre-dose and End of infusion on Day 1, 3 and 5 of each cycle; 1, 3 and 6 hour after the end of infusion on Day 1 of each cycle
measure: Number of Participants With Positive Anti-Drug Antibody
timeFrame: Baseline (Day 1) up to End of the Treatment (Last dose of Last cycle) (approximately 3 years)
measure: Number of Participants With CD22 Expression Levels
timeFrame: Baseline (Day 1) up to End of the Treatment (Last dose of Last cycle) (approximately 3 years)
measure: Number of Capillary Leak Syndrome (CLS) Participants With Weight Changes, Albumin, Hypotension, Edema, Hypoxia, and Pulmonary Adverse Events (AEs)
timeFrame: From Screening (Day -28) to Post Therapy Day 30
measure: Percentage of Participants With Stable Disease (SD)
timeFrame: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Bethesda
country: United States
facility: Research Site
state: Maryland
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Charleston
country: United States
facility: Research Site
state: South Carolina
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Temple
country: United States
facility: Research Site
state: Texas
city: Łódź
country: Poland
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: Ramy Ibrahim, M.D.
role: STUDY_DIRECTOR
References: