Non-Hodgkin Lymphoma
Conditions
Keywords
Lymphoma
Brief summary
This research study is studying Blinatumomab as a possible treatment for Indolent Non-Hodgkin Lymphoma (NHL).
Detailed description
This research study is a Phase II clinical trial. The overall purpose of this study is to determine if blinatumomab is safe and effective for treating adult subjects with relapsed or refractory indolent B cell NHL. Blinatumomab will be infused causing T cells to recognize the Cancer and work against them. This approach has been FDA approved for acute lymphocytic leukemia but has not yet been approved for lymphoma.
Interventions
DRUGBlinatumomab
Blinatumomab is a bispecific t cell engaging antibody targeting CD19 and CD3 approved for B cell acute lymphoblastic leukemia
Sponsors
Amgen
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must have histologically determined B cell NHL that is relapsed or primary refractory after initial therapy. * Follicular Lymphoma of any grade * Marginal zone lymphoma (extranodal, nodal, or splenic). Patients with gastric MALT must have progressed after H. Pylori therapy and radiation. Patients with splenic MZL must have prior splenectomy. * At least 1 prior line of chemoimmunotherapy if primary refractory or relapsed with in one year. Subjects who respond to initial therapy for greater than one year must have had at least 2 prior lines of therapy including one line with chemoimmunotherapy including an anti-CD20 monoclonal antibody * Measurable disease that has not been previously irradiated on PET-CT of at least 1.5cm, * Age ≥18 years. * ECOG performance status ≤2 ( see Appendix A) * Participants must have adequate organ and marrow function as defined below: * absolute neutrophil count ≥750/mcL * platelets ≥75,000/mcL * total bilirubin \< 2.0 x upper limit of normal (ULN) * AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal or 5 X ULN * if due to lymphoma infiltration * creatinine 2.0 X ULN OR * creatinine clearance ≥50 mL/min/1.73 m2 for participants with creatinine levels above 2.0 X ULN . * Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
* Participants who have had chemotherapy within 3 weeks, rituximab or obinutuzumab within 4 weeks, or radioimmunotherapy within 6 weeks prior to entering the study, or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier. Subjects actively progressing within that window who have recovered from toxicities of prior therapy are also eligible. * Autologous stem cell transplantation within 12 weeks prior to study entry * Prior allogeneic transplant * Therapeutic doses of corticosteroids within 14 days prior to study entry, defined as \>20mg/day pf prednisone, or equivalent. Topical and/or inhaled steroids are permitted. * Participants who are receiving any other investigational agents. * Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to blinatumomab * Subjects with known HIV infection * Pregnant or lactating subjects. * Chronic infection with hepatitis B or hepatitis C virus * History of or current relevant CNS pathology such as epilepsy, seizure, paresis,aphasia, apoplexia, severe brain injuries, cerebellar disease, organic brain syndrome, psychosis * Prior history of another malignancy (except for non-melanoma skin cancer, in situ cervical or breast cancer, or localized prostate cancer) unless disease free for at least one year and felt at low risk of relapse by treating physician. * Uncontrolled intercurrent illness including, but not limited to, ongoing or uncontrolled systemic fungal, bacterial, viral, or other infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | at completion of treatment (6 months) | Count of participants achieving a complete or partial response according to the revised response criteria for malignant lymphoma (2014). A complete response is defined as regression of involved nodes to normal size (1.5 cm or less in their greatest transverse diameter for nodes 1.5 cm or greater before therapy). Involved nodes 1.1 - 1.5 cm in their greatest transverse diameter before treatment must have decreased to less than 1 cm in their greatest transverse diameter after treatment, or by more than 75% in the sum of the products of the greatest diameters (SPD). For a complete response, the spleen, if enlarged before therapy on a CT scan, must also have regressed in size and must not be palpable. A partial response is defined as 50% or greater decrease in SPD of up to 6 largest dominant masses. There must also be no new sites of disease or increases in the size of the other nodes, liver, or spleen. Splenic/hepatic nodules must regress by at least 50% in SPD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | 5 years | Progression free survival is defined as the duration of time from start of treatment to time of documentation of disease progression according to the revised response criteria for malignant lymphoma (2014), death, or loss to follow-up. Progressive disease is defined as appearance of a new PET positive lesion greater than 1.5 cm in any axis, 50% or greater increase in the sum of the products of the greatest diameters (SPD) of more than one node, 50% or greater increase in longest diameter of a previously identified node less than 1 cm in short axis. There must also be a 50% increase from nadir in the SPD of any previous lesions. |
| Time To Response Rate | 4 months | Time to response is defined as the duration of time from start of treatment to the achievement of a complete response (CR) or partial response (PR) according to the revised response criteria for malignant lymphoma (2014). A CR is defined as regression of involved nodes to normal size (1.5 cm or less in their greatest transverse diameter for nodes 1.5 cm or greater before therapy). Involved nodes 1.1 - 1.5 cm in their greatest transverse diameter before treatment must have decreased to less than 1 cm in this measure after treatment, or by more than 75% in the sum of the products of the greatest diameters (SPD). For a CR, the spleen, if enlarged before therapy on a CT scan, must also have regressed in size and must not be palpable. A PR is defined as 50% or greater decrease in SPD of up to 6 largest dominant masses. There must also be no new sites of disease or increases in the size of the other nodes, liver, or spleen. Splenic/hepatic nodules must regress by at least 50% in SPD. |
| Duration of Response | 5 years | Duration of response is defined as the time from response (complete or partial response according to the revised response criteria for malignant lymphoma 2014) to disease progression, death, or loss to follow-up. |
| Rate Patients Are Discontinued From The Drug Due to Toxicity | 2 years | Number of patients who discontinued study treatment early due to one or more toxicities. |
| Overall Survival | 5 years | Overall survival is defined the duration of time from start of treatment to time of death or loss to follow up. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Blinatumomab Blinatumomab will be administered as a continuous IV infusion through a central venous catheter for a 42 day cycle. Blinatumomab will start with a 7 day infusion at 9mcg/d. If no dose limiting toxicity (table 6.1) after 7 days, the dose will be escalated to 28 mcg/d for 7 additional days. If no dose limiting toxicity (table 6.1) after 14 days, blinatumomab will be infused at a target dose of at 112mcg/d for 28 days. Subjects will be restaged after a 6 week treatment free period by PET CT. All subjects without disease progression will receive an additional 4 week cycle starting at the target dose of 112 mcg/d.
Blinatumomab: Blinatumomab is a bispecific t cell engaging antibody targeting CD19 and CD3 approved for B cell acute lymphoblastic leukemia | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Early study closure due to slow accrual | 3 |
| Overall Study | Lack of Efficacy | 6 |
Baseline characteristics
| Characteristic | Blinatumomab |
|---|---|
| Age, Continuous | 62 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 13 |
| other Total, other adverse events | 12 / 13 |
| serious Total, serious adverse events | 6 / 13 |
Outcome results
Primary
Overall Response Rate (ORR)
Count of participants achieving a complete or partial response according to the revised response criteria for malignant lymphoma (2014). A complete response is defined as regression of involved nodes to normal size (1.5 cm or less in their greatest transverse diameter for nodes 1.5 cm or greater before therapy). Involved nodes 1.1 - 1.5 cm in their greatest transverse diameter before treatment must have decreased to less than 1 cm in their greatest transverse diameter after treatment, or by more than 75% in the sum of the products of the greatest diameters (SPD). For a complete response, the spleen, if enlarged before therapy on a CT scan, must also have regressed in size and must not be palpable. A partial response is defined as 50% or greater decrease in SPD of up to 6 largest dominant masses. There must also be no new sites of disease or increases in the size of the other nodes, liver, or spleen. Splenic/hepatic nodules must regress by at least 50% in SPD.
Time frame: at completion of treatment (6 months)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Blinatumomab | Overall Response Rate (ORR) | 6 Participants |
Secondary
Duration of Response
Duration of response is defined as the time from response (complete or partial response according to the revised response criteria for malignant lymphoma 2014) to disease progression, death, or loss to follow-up.
Time frame: 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Blinatumomab | Duration of Response | 30.0 months |
Secondary
Overall Survival
Overall survival is defined the duration of time from start of treatment to time of death or loss to follow up.
Time frame: 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Blinatumomab | Overall Survival | NA months |
Secondary
Progression Free Survival
Progression free survival is defined as the duration of time from start of treatment to time of documentation of disease progression according to the revised response criteria for malignant lymphoma (2014), death, or loss to follow-up. Progressive disease is defined as appearance of a new PET positive lesion greater than 1.5 cm in any axis, 50% or greater increase in the sum of the products of the greatest diameters (SPD) of more than one node, 50% or greater increase in longest diameter of a previously identified node less than 1 cm in short axis. There must also be a 50% increase from nadir in the SPD of any previous lesions.
Time frame: 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Blinatumomab | Progression Free Survival | 4.0 months |
Secondary
Rate Patients Are Discontinued From The Drug Due to Toxicity
Number of patients who discontinued study treatment early due to one or more toxicities.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Blinatumomab | Rate Patients Are Discontinued From The Drug Due to Toxicity | 1 Participants |
Secondary
Time To Response Rate
Time to response is defined as the duration of time from start of treatment to the achievement of a complete response (CR) or partial response (PR) according to the revised response criteria for malignant lymphoma (2014). A CR is defined as regression of involved nodes to normal size (1.5 cm or less in their greatest transverse diameter for nodes 1.5 cm or greater before therapy). Involved nodes 1.1 - 1.5 cm in their greatest transverse diameter before treatment must have decreased to less than 1 cm in this measure after treatment, or by more than 75% in the sum of the products of the greatest diameters (SPD). For a CR, the spleen, if enlarged before therapy on a CT scan, must also have regressed in size and must not be palpable. A PR is defined as 50% or greater decrease in SPD of up to 6 largest dominant masses. There must also be no new sites of disease or increases in the size of the other nodes, liver, or spleen. Splenic/hepatic nodules must regress by at least 50% in SPD.
Time frame: 4 months
Population: The 5 patients who achieved a response were included in the analysis; those who did not achieve a partial response or better were excluded.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Blinatumomab | Time To Response Rate | 2.8 months |