Non-Hodgkin LymphomaPhase 1/2NCT01030536
Safety Study of CAT-8015 to Treat Advanced B-cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (NHL or CLL)
A Phase 1/2 study testing CAT-8015 20 mcg/kg, CAT-8015 30 mcg/kg and CAT-8015 40 mcg/kg in people with Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia, run by MedImmune LLC at 8 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia
- What is being tested?
- CAT-8015 20 mcg/kg, CAT-8015 30 mcg/kg and CAT-8015 40 mcg/kg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 8 sitesin 2 countries
- Study dates
- 15 Feb 2010to 4 Mar 2013
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
United States7 sites
Research Site
Bethesda, Maryland, 20892
Research Site
Charleston, South Carolina, 29424
Research Site
Indianapolis, Indiana, 46202
Research Site
Las Vegas, Nevada, 89169
Research Site
Los Angeles, California
Research Site
Nashville, Tennessee, 37203
Research Site
Temple, Texas, 76508
About this study
Official title: A Phase 1/2 Study of CAT-8015 in Adult Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia
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.
Read the 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.
- Conditions
- Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia
- Being tested
- CAT-8015 20 mcg/kg, CAT-8015 30 mcg/kg, CAT-8015 40 mcg/kg, CAT-8015 50 mcg/kg, CAT-8015 60 mcg/kg
- Keywords
- NHL, CLL
- Medical subject headings
- Lymphoma, Non-Hodgkin, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAT-8015 20 mcg/kgDrug
Participants will receive 20 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle.
CAT-8015 30 mcg/kgDrug
Participants will receive 30 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle.
CAT-8015 40 mcg/kgDrug
Participants will receive 40 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle.
CAT-8015 50 mcg/kgDrug
Participants will receive 50 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle.
CAT-8015 60 mcg/kgDrug
Participants will receive 60 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| CAT-8015 20 microgram per kilogram (mcg/kg) | Experimental | Participants will receive 20 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation is to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 mcg/kg. Receives: Drug: CAT-8015 20 mcg/kg |
| CAT-8015 30 mcg/kg | Experimental | Participants will receive 30 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation is to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 mcg/kg. Receives: Drug: CAT-8015 30 mcg/kg |
| CAT-8015 40 mcg/kg | Experimental | Participants will receive 40 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation is to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 mcg/kg. Receives: Drug: CAT-8015 40 mcg/kg |
| CAT-8015 50 mcg/kg | Experimental | Participants will receive 50 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation is to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 mcg/kg. Receives: Drug: CAT-8015 50 mcg/kg |
| CAT-8015 60 mcg/kg | Experimental | Participants will receive 60 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation is to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 mcg/kg. Receives: Drug: CAT-8015 60 mcg/kg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
MTD reflects highest dose of drug that did not cause an unacceptable side effect (= Dose Limiting Toxicity [DLT]) in more than 30 percent (%) of participants.
Measured: Day 1 to end of Cycle 1 (approximately 28 days)
Number of Participants With Dose Limiting Toxicities (DLTs)
Any Grade 3 or greater, non-hematological toxicity (including capillary leak syndrome [CLS] and thrombotic microangiopathy/ hemolytic uremic syndrome (HUS), Grade 3 or higher treatment-related hematologic toxicities and only ≥ Grade 3 thrombotic microangiopathy /HUS constituted a DLT with few exceptions.
Measured: Day 1 to end of Cycle 1 (approximately 28 days)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An Serious Adverse Event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Measured: From Screening (Day -28) to Post Therapy Day 30
Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Measured: From Screening (Day -28) to Post Therapy Day 30
Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Measured: From Screening (Day -28) to Post Therapy Day 30
Number of Participants With Electrocardiogram (ECG) Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Measured: From Screening (Day -28) to Post Therapy Day 30
Secondary outcomes (15)
Percentage of Participants With Complete Response (CR)
The CR rate was defined as the percentage of participants who had achieved CR based on both the evaluable population for efficacy.
Measured: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Duration of Complete Response
Duration of CR was measured from the first documentation of a CR to the time of relapse for the subgroup of participants with CR. Duration of CR was calculated using the Kaplan Meier method. The Evaluable Population for efficacy was used to evaluate the endpoints for the efficacy profile.
Measured: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Percentage of Participants With Partial Response (PR)
Measured: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Percentage of Participants With Objective Response (OR)
OR was defined as the percentage of participants with CR or partial response (PR).
Measured: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Time to Response (TTR)
TTR was measured from the start of moxetumomab pasudotox administration to the first documentation of response (CR or PR) and was only assessed in participants who had achieved objective response (OR).
Measured: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Duration of Objective Response (DOR)
DOR was measured from the first documentation of OR to the event of relapse. DOR was calculated using the Kaplan-Meier method.
Measured: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Duration of Stable Disease (SD)
Duration of SD was defined as the time period from start of moxetumomab pasudotox administration to the event of progressive disease (PD)/relapse. Duration of SD was only calculated for the subgroup of participants with best response of CR, PR, or SD, and was calculated using the Kaplan-Meier method.
Measured: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Maximum Plasma Concentration (Cmax) of Moxetumomab Pasudotox
Maximum observed drug concentration of Moxetumomab pasudotox in plasma.
Measured: 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
Area Under Concentration-Time Curve From Dosing Extrapolated to Infinity (AUCinf) of Moxetumomab Pasudotox
Area under the concentration versus time curve from zero to infinity (AUC) of Moxetumomab pasudotox in Plasma.
Measured: 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
Clearance (CL) of Moxetumomab Pasudotox
CL of drug is rate at which drug is metabolized or eliminated by normal biological processes and is influenced by fraction of dose absorbed.
Measured: 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
Elimination Half Life (t1/2) of Moxetumomab Pasudotox
Plasma decay half life is the time measured for the plasma concentration to decrease by one half.
Measured: 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
Number of Participants With Positive Anti-Drug Antibody
The moxetumomab pasudotox specific bridging assay using the Meso Scale Discovery platform was employed to detect anti-drug antibodies (ADA).
Measured: Baseline (Day 1) up to End of the Treatment (Last dose of Last cycle) (approximately 3 years)
Number of Participants With CD22 Expression Levels
CD22 Expression was analyzed using Prism® analysis. Flow cytometry was performed to quantitate the CD22 expression for the purpose of evaluating the relationship of CD22 expression with response to treatment.
Measured: Baseline (Day 1) up to End of the Treatment (Last dose of Last cycle) (approximately 3 years)
Number of Capillary Leak Syndrome (CLS) Participants With Weight Changes, Albumin, Hypotension, Edema, Hypoxia, and Pulmonary Adverse Events (AEs)
The correlation of CLS and weight changes, albumin, hypotension, edema, hypoxia, and pulmonary AEs were examined.
Measured: From Screening (Day -28) to Post Therapy Day 30
Percentage of Participants With Stable Disease (SD)
Measured: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2009 (estimated)
- Study start15 Feb 2010
- Primary completion4 Mar 2013
- Study completion4 Mar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-Hodgkin LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- MedImmune LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ramy Ibrahim, M.D., Study director, MedImmune LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01030536
- Sponsor's protocol ID
- MI-CP218
- Status last verified
- Mar 2018
- First submitted
- 9 Dec 2009
- Last updated
- 9 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study of CAT-8015 in Adult Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT01030536
- Acronym / sponsor ID
- MI-CP218
- Conditions
- Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia
- Keywords
- NHL, CLL
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- MedImmune LLCIndustry (pharma, biotech, devices)
- Study start
- 15 Feb 2010 (actual)
- Primary completion
- 4 Mar 2013 (actual)
- Study completion
- 4 Mar 2013 (actual)
- First posted
- 11 Dec 2009 (estimated)
- Results
- Posted 9 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| CAT-8015 20 microgram per kilogram (mcg/kg) | Experimental | Drug: CAT-8015 20 mcg/kgParticipants will receive 20 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation is to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 mcg/kg. |
| CAT-8015 30 mcg/kg | Experimental | Drug: CAT-8015 30 mcg/kgParticipants will receive 30 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation is to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 mcg/kg. |
| CAT-8015 40 mcg/kg | Experimental | Drug: CAT-8015 40 mcg/kgParticipants will receive 40 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation is to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 mcg/kg. |
| CAT-8015 50 mcg/kg | Experimental | Drug: CAT-8015 50 mcg/kgParticipants will receive 50 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation is to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 mcg/kg. |
| CAT-8015 60 mcg/kg | Experimental | Drug: CAT-8015 60 mcg/kgParticipants will receive 60 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation is to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 mcg/kg. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CAT-8015 20 mcg/kgParticipants will receive 20 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. | Drug | CAT-8015 20 microgram per kilogram (mcg/kg) |
| CAT-8015 30 mcg/kgParticipants will receive 30 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. | Drug | CAT-8015 30 mcg/kg |
| CAT-8015 40 mcg/kgParticipants will receive 40 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. | Drug | CAT-8015 40 mcg/kg |
| CAT-8015 50 mcg/kgParticipants will receive 50 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. | Drug | CAT-8015 50 mcg/kg |
| CAT-8015 60 mcg/kgParticipants will receive 60 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. | Drug | CAT-8015 60 mcg/kg |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: Day 1 to end of Cycle 1 (approximately 28 days)
MTD reflects highest dose of drug that did not cause an unacceptable side effect (= Dose Limiting Toxicity [DLT]) in more than 30 percent (%) of participants.
Number of Participants With Dose Limiting Toxicities (DLTs)
Time frame: Day 1 to end of Cycle 1 (approximately 28 days)
Any Grade 3 or greater, non-hematological toxicity (including capillary leak syndrome [CLS] and thrombotic microangiopathy/ hemolytic uremic syndrome (HUS), Grade 3 or higher treatment-related hematologic toxicities and only ≥ Grade 3 thrombotic microangiopathy /HUS constituted a DLT with few exceptions.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Time frame: From Screening (Day -28) to Post Therapy Day 30
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An Serious Adverse Event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
Time frame: From Screening (Day -28) to Post Therapy Day 30
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
Time frame: From Screening (Day -28) to Post Therapy Day 30
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Number of Participants With Electrocardiogram (ECG) Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
Time frame: From Screening (Day -28) to Post Therapy Day 30
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
15 secondary outcomes
Percentage of Participants With Complete Response (CR)
Time frame: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Duration of Complete Response
Time frame: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Percentage of Participants With Partial Response (PR)
Time frame: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Percentage of Participants With Objective Response (OR)
Time frame: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Time to Response (TTR)
Time frame: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Duration of Objective Response (DOR)
Time frame: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Duration of Stable Disease (SD)
Time frame: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Maximum Plasma Concentration (Cmax) of Moxetumomab Pasudotox
Time frame: 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
Area Under Concentration-Time Curve From Dosing Extrapolated to Infinity (AUCinf) of Moxetumomab Pasudotox
Time frame: 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
Clearance (CL) of Moxetumomab Pasudotox
Time frame: 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
Elimination Half Life (t1/2) of Moxetumomab Pasudotox
Time frame: 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
Number of Participants With Positive Anti-Drug Antibody
Time frame: Baseline (Day 1) up to End of the Treatment (Last dose of Last cycle) (approximately 3 years)
Number of Participants With CD22 Expression Levels
Time frame: Baseline (Day 1) up to End of the Treatment (Last dose of Last cycle) (approximately 3 years)
Number of Capillary Leak Syndrome (CLS) Participants With Weight Changes, Albumin, Hypotension, Edema, Hypoxia, and Pulmonary Adverse Events (AEs)
Time frame: From Screening (Day -28) to Post Therapy Day 30
Percentage of Participants With Stable Disease (SD)
Time frame: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ramy Ibrahim, M.D. study director
MedImmune LLC
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CAT-8015 20 mcg/kg, CAT-8015 30 mcg/kg and CAT-8015 40 mcg/kg in people with Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia, run by MedImmune LLC at 8 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) (time frame: Day 1 to end of Cycle 1 (approximately 28 days)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2018.