B-cell Chronic Lymphocytic Leukemia, Multiple Myeloma
Conditions
Keywords
B-cell Chronic Lymphocytic Leukemia, Leukemia, Multiple Myeloma, CD200, Anti-CD200
Brief summary
The purpose of this study was to determine the safety and maximum tolerated dose (MTD) of ALXN6000 (samalizumab) in treating relapsing or refractory B-cell chronic lymphocytic leukemia (B-CLL) or multiple myeloma (MM) and to study how samalizumab may help the immune system fight tumors that express CD200.
Detailed description
This was an open-label multicenter study for participants with relapsing or refractory B-CLL or MM. The study was planned to be conducted in 2 parts: Part A and Part B. Both parts were to evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy (to the extent possible) of samalizumab in the target participant population. Part A was designed as the open-label, intravenous (IV) single dose-escalation portion of the study to determine the MTD and to assess the overall safety of different dose levels of up to 4 IV doses of samalizumab in participants with either refractory or relapsing B-CLL or MM. Initially, at least 3 participants would be enrolled into a cohort until a dose-limiting toxicity (DLT) was reached. If any 1 of the initial 3 participants in the cohort experienced a DLT, the cohort would be expanded to at least 6 participants. After determination of the MTD in Part A, the Sponsor was to review the safety, PK, and relevant PD data to determine the dosing administration schedule for Part B. However, no participants were enrolled for Part B, as the study was terminated by the Sponsor for administrative reasons. Participant enrollment in Cohort 7 (600 milligrams per square meter \[mg/m\^2\] dose level), Part A, was halted after enrollment of the first participant. The study was terminated by the Sponsor for administrative reasons and not due to any safety concerns. Participants who were on study at the time of study termination were allowed to continue until the expiry date of the drug lot being used and then were followed for 30 (±1) days per protocol. The study was terminated by the Sponsor at that time. Part B of the study was not conducted.
Interventions
DRUGSamalizumab
Samalizumab is a humanized anti-CD200 monoclonal antibody.
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Relapsing or Refractory B-CLL or MM * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 * Anticipated survival of greater than 6 months * Female participants of childbearing potential must agree to use 2 forms of contraception * Participants must have a standard indication for treatment of their malignancy * Is willing and able to give written informed consent prior to any procedure not considered standard of care
Exclusion criteria
* Absolute neutrophil count (ANC) \< 1000 x 10\^9/liter (L) * Platelet count \< 50,000 x 10\^9/L * Pregnant or lactating women * Prior history of autoimmune hemolysis requiring therapy * Prior history of immune thrombocytopenia * Active autoimmune disease requiring immunosuppressive therapy * Positive Coombs' Test (neither direct or indirect) * Ongoing corticosteroid treatment equivalent to the mineralocorticoid potency of 10 milligrams (mg) /day of prednisone, or greater, for any condition * Prior stem cell transplantation within 4 weeks prior to enrollment * Prior chemotherapy for the applicable malignancy within 30 days of enrollment * Neurosurgery or cranial radiation therapy within 1 year of enrollment * Clinically significant renal, hepatic, or cardiopulmonary disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) Of Samalizumab | From first dose through 10 weeks after the last dose | The MTD was to be defined as the dose level at which less than one-third of participants experienced a dose-limiting toxicity (DLT) during the first 28 days of treatment and immediately below the dose at which at least one-third of participants experienced a DLT. A DLT was defined as any Grade 3 or greater toxicity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 not related to the disease under study or its sequelae that occurred in the first 28 days after dosing in Cycle 1. The NCI CTCAE grading system for the organ of involvement was used to classify severity of adverse autoimmune reactions. |
| Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | From first dose through 10 weeks after the last dose | A TEAE was defined as any event not present prior to exposure to samalizumab or any event already present that worsened in either intensity or frequency following exposure to samalizumab. A treatment-emergent serious adverse event was defined as any event that resulted in death, was immediately life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Of Bound Samalizumab On B-Cell Chronic Lymphocytic Leukemia (B-CLL) Cells In Participants With B-CLL At Baseline (Predose) And Day 1 (Postdose) | Baseline (Predose) and Day 1 (Postdose) | Bound samalizumab was detected using a monoclonal antibody (mAb) specific for samalizumab. The binding of samalizumab to CD200 on peripheral B-CLL tumor cells was evaluated in participants with B-CLL by flow cytometry and expressed as the percent of B-CLL cells bound by samalizumab. For participants with insufficient numbers of peripheral B-CLL for analysis, the samples were documented as unevaluable and an analysis was not performed. |
| Density Of B-CLL Cells Bound At Baseline (Predose) And Day 1 (Postdose) | Baseline (Predose) and Day 1 (Postdose) | Bound samalizumab was detected using a mAb specific for samalizumab. The binding of samalizumab to CD200 on peripheral B-CLL tumor cells was evaluated in participants with B-CLL by flow cytometry and expressed as mean channel fluorescence intensity (MFI) of bound samalizumab to provide an indication of the density of bound samalizumab on target B-CLL cells. For participants with insufficient numbers of peripheral B-CLL for analysis, the samples were documented as unevaluable and an analysis was not performed. |
| Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | From first dose through 10 weeks after the last dose | Clinical responses assessed using the Modified NCI Working Group Response Criteria. Overall Response Rate (ORR)=percentage of participants who maintained best response for ≥1 month after achieving that best response and having complete response (CR), partial response (PR), nodular partial response (nPR), or stable disease (SD). CR=absence of lymphadenopathy, hepatomegaly, or splenomegaly and normal complete blood count (CBC). PR=≥50% decrease in peripheral lymphocyte count or ≥50% reduction in lymphadenopathy, hepatomegaly, or splenomegaly and normal or 50% improvement over baseline CBC. nPR=CR participants with lymphoid aggregates. Progressive disease (PD)=\>50% increase for \>2 lymph nodes, spleen and/or liver size, or absolute number of circulating lymphocytes; or new lymph nodes. SD=have not achieved CR, PR, or nPR or have not shown PD. Features must be exhibited for ≥1month for CR/PR. Number of participants with individual best response and ORR for each cohort is presented. |
| Clinical Response Of Participants With Multiple Myeloma (MM) Following Dosing With Samalizumab | From first dose through 10 weeks after the last dose | Clinical responses of samalizumab were assessed using the International Myeloma Working Group Uniform Response Criteria. ORR was defined as the percentage of participants who had either stringent complete response, complete response, very good partial response, or partial response on 2 consecutive assessments made at any time before the administration of any new therapy. The number of participants with the individual best response and ORR for each cohort is presented. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Samalizumab All doses of samalizumab were individualized based on the participant's body surface area in mg/m\^2 based on screening height and weight. Participants were assigned to a dose cohort, ranging from 50 to 600 mg/m\^2, and received a single IV dose of samalizumab. Participants who tolerated the drug and demonstrated at least stable disease received up to 3 additional cycles of samalizumab at the same dose originally received at a minimum of 28-day intervals and beginning no sooner than 6 weeks after the initial dose. | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 | 2 | 1 | 0 | 0 |
| Overall Study | Death | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Follow-up Visits Not Completed | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Investigator Considered it Advisable | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Lack of Efficacy | 0 | 0 | 0 | 0 | 1 | 2 | 0 |
| Overall Study | Positive Human Anti-human Antibody | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 0 | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Samalizumab |
|---|---|
| Age, Continuous | 65.8629 years STANDARD_DEVIATION 12.14 |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 18 Participants |
| Type of Malignancy B-Cell Chronic Lymphocytic Leukemia | 23 Participants |
| Type of Malignancy Multiple Myeloma | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 1 / 5 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 7 | 0 / 1 |
| other Total, other adverse events | 4 / 4 | 5 / 5 | 3 / 3 | 3 / 3 | 3 / 3 | 6 / 7 | 1 / 1 |
| serious Total, serious adverse events | 1 / 4 | 2 / 5 | 0 / 3 | 1 / 3 | 1 / 3 | 1 / 7 | 0 / 1 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) Of Samalizumab
The MTD was to be defined as the dose level at which less than one-third of participants experienced a dose-limiting toxicity (DLT) during the first 28 days of treatment and immediately below the dose at which at least one-third of participants experienced a DLT. A DLT was defined as any Grade 3 or greater toxicity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 not related to the disease under study or its sequelae that occurred in the first 28 days after dosing in Cycle 1. The NCI CTCAE grading system for the organ of involvement was used to classify severity of adverse autoimmune reactions.
Time frame: From first dose through 10 weeks after the last dose
Population: All participants who received at least 1 dose of samalizumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Samalizumab | Maximum Tolerated Dose (MTD) Of Samalizumab | NA mg/m^2 |
Primary
Number Of Participants With Treatment-Emergent Adverse Events (TEAEs)
A TEAE was defined as any event not present prior to exposure to samalizumab or any event already present that worsened in either intensity or frequency following exposure to samalizumab. A treatment-emergent serious adverse event was defined as any event that resulted in death, was immediately life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: From first dose through 10 weeks after the last dose
Population: All participants who received at least 1 dose of samalizumab.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Samalizumab | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | At Least 1 TEAE | 4 participants |
| Samalizumab | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-emergent Serious Adverse Event | 1 participants |
| Samalizumab | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Discontinued due to Adverse Events | 1 participants |
| Samalizumab | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Adverse Events Leading to Death | 0 participants |
| Samalizumab 100 mg/m^2 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Adverse Events Leading to Death | 1 participants |
| Samalizumab 100 mg/m^2 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-emergent Serious Adverse Event | 2 participants |
| Samalizumab 100 mg/m^2 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | At Least 1 TEAE | 5 participants |
| Samalizumab 100 mg/m^2 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Discontinued due to Adverse Events | 0 participants |
| Samalizumab 200 mg/m^2 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-emergent Serious Adverse Event | 0 participants |
| Samalizumab 200 mg/m^2 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Adverse Events Leading to Death | 0 participants |
| Samalizumab 200 mg/m^2 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | At Least 1 TEAE | 3 participants |
| Samalizumab 200 mg/m^2 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Discontinued due to Adverse Events | 1 participants |
| Samalizumab 300 mg/m^2 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Adverse Events Leading to Death | 0 participants |
| Samalizumab 300 mg/m^2 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | At Least 1 TEAE | 3 participants |
| Samalizumab 300 mg/m^2 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-emergent Serious Adverse Event | 1 participants |
| Samalizumab 300 mg/m^2 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Discontinued due to Adverse Events | 2 participants |
| Samalizumab 400 mg/m^2 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-emergent Serious Adverse Event | 1 participants |
| Samalizumab 400 mg/m^2 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Discontinued due to Adverse Events | 1 participants |
| Samalizumab 400 mg/m^2 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | At Least 1 TEAE | 3 participants |
| Samalizumab 400 mg/m^2 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Adverse Events Leading to Death | 0 participants |
| Samalizumab 500 mg/m^2 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | At Least 1 TEAE | 6 participants |
| Samalizumab 500 mg/m^2 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-emergent Serious Adverse Event | 1 participants |
| Samalizumab 500 mg/m^2 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Adverse Events Leading to Death | 0 participants |
| Samalizumab 500 mg/m^2 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Discontinued due to Adverse Events | 0 participants |
| Samalizumab 600 mg/m^2 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | At Least 1 TEAE | 1 participants |
| Samalizumab 600 mg/m^2 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Discontinued due to Adverse Events | 0 participants |
| Samalizumab 600 mg/m^2 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Adverse Events Leading to Death | 0 participants |
| Samalizumab 600 mg/m^2 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-emergent Serious Adverse Event | 0 participants |
| Overall | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Adverse Events Leading to Death | 1 participants |
| Overall | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | At Least 1 TEAE | 25 participants |
| Overall | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-emergent Serious Adverse Event | 6 participants |
| Overall | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Discontinued due to Adverse Events | 5 participants |
Secondary
Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate
Clinical responses assessed using the Modified NCI Working Group Response Criteria. Overall Response Rate (ORR)=percentage of participants who maintained best response for ≥1 month after achieving that best response and having complete response (CR), partial response (PR), nodular partial response (nPR), or stable disease (SD). CR=absence of lymphadenopathy, hepatomegaly, or splenomegaly and normal complete blood count (CBC). PR=≥50% decrease in peripheral lymphocyte count or ≥50% reduction in lymphadenopathy, hepatomegaly, or splenomegaly and normal or 50% improvement over baseline CBC. nPR=CR participants with lymphoid aggregates. Progressive disease (PD)=\>50% increase for \>2 lymph nodes, spleen and/or liver size, or absolute number of circulating lymphocytes; or new lymph nodes. SD=have not achieved CR, PR, or nPR or have not shown PD. Features must be exhibited for ≥1month for CR/PR. Number of participants with individual best response and ORR for each cohort is presented.
Time frame: From first dose through 10 weeks after the last dose
Population: All participants with B-CLL who received at least 1 dose of samalizumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Samalizumab | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | ORR | 0 Participants |
| Samalizumab | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | Partial Response | 0 Participants |
| Samalizumab | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | Progressive Disease | 1 Participants |
| Samalizumab | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | Not Evaluable | 0 Participants |
| Samalizumab | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | Stable Disease | 3 Participants |
| Samalizumab 100 mg/m^2 | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | Not Evaluable | 0 Participants |
| Samalizumab 100 mg/m^2 | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | Progressive Disease | 1 Participants |
| Samalizumab 100 mg/m^2 | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | Partial Response | 0 Participants |
| Samalizumab 100 mg/m^2 | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | Stable Disease | 4 Participants |
| Samalizumab 100 mg/m^2 | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | ORR | 0 Participants |
| Samalizumab 200 mg/m^2 | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | Partial Response | 0 Participants |
| Samalizumab 200 mg/m^2 | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | ORR | 0 Participants |
| Samalizumab 200 mg/m^2 | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | Progressive Disease | 0 Participants |
| Samalizumab 200 mg/m^2 | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | Not Evaluable | 1 Participants |
| Samalizumab 200 mg/m^2 | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | Stable Disease | 2 Participants |
| Samalizumab 300 mg/m^2 | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | Partial Response | 0 Participants |
| Samalizumab 300 mg/m^2 | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | Progressive Disease | 0 Participants |
| Samalizumab 300 mg/m^2 | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | Stable Disease | 3 Participants |
| Samalizumab 300 mg/m^2 | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | ORR | 0 Participants |
| Samalizumab 300 mg/m^2 | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | Not Evaluable | 0 Participants |
| Samalizumab 400 mg/m^2 | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | Progressive Disease | 1 Participants |
| Samalizumab 400 mg/m^2 | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | Partial Response | 1 Participants |
| Samalizumab 400 mg/m^2 | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | Stable Disease | 1 Participants |
| Samalizumab 400 mg/m^2 | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | Not Evaluable | 0 Participants |
| Samalizumab 400 mg/m^2 | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | ORR | 1 Participants |
| Samalizumab 500 mg/m^2 | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | Stable Disease | 3 Participants |
| Samalizumab 500 mg/m^2 | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | Partial Response | 0 Participants |
| Samalizumab 500 mg/m^2 | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | Progressive Disease | 2 Participants |
| Samalizumab 500 mg/m^2 | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | ORR | 0 Participants |
| Samalizumab 500 mg/m^2 | Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate | Not Evaluable | 0 Participants |
Secondary
Clinical Response Of Participants With Multiple Myeloma (MM) Following Dosing With Samalizumab
Clinical responses of samalizumab were assessed using the International Myeloma Working Group Uniform Response Criteria. ORR was defined as the percentage of participants who had either stringent complete response, complete response, very good partial response, or partial response on 2 consecutive assessments made at any time before the administration of any new therapy. The number of participants with the individual best response and ORR for each cohort is presented.
Time frame: From first dose through 10 weeks after the last dose
Population: All participants with MM who received at least 1 dose of samalizumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Samalizumab | Clinical Response Of Participants With Multiple Myeloma (MM) Following Dosing With Samalizumab | Partial Response | 0 Participants |
| Samalizumab | Clinical Response Of Participants With Multiple Myeloma (MM) Following Dosing With Samalizumab | Not Evaluable | 0 Participants |
| Samalizumab | Clinical Response Of Participants With Multiple Myeloma (MM) Following Dosing With Samalizumab | Stable Disease | 0 Participants |
| Samalizumab | Clinical Response Of Participants With Multiple Myeloma (MM) Following Dosing With Samalizumab | ORR | 0 Participants |
| Samalizumab | Clinical Response Of Participants With Multiple Myeloma (MM) Following Dosing With Samalizumab | Progressive Disease | 2 Participants |
| Samalizumab 100 mg/m^2 | Clinical Response Of Participants With Multiple Myeloma (MM) Following Dosing With Samalizumab | ORR | 0 Participants |
| Samalizumab 100 mg/m^2 | Clinical Response Of Participants With Multiple Myeloma (MM) Following Dosing With Samalizumab | Progressive Disease | 1 Participants |
| Samalizumab 100 mg/m^2 | Clinical Response Of Participants With Multiple Myeloma (MM) Following Dosing With Samalizumab | Partial Response | 0 Participants |
| Samalizumab 100 mg/m^2 | Clinical Response Of Participants With Multiple Myeloma (MM) Following Dosing With Samalizumab | Stable Disease | 0 Participants |
| Samalizumab 100 mg/m^2 | Clinical Response Of Participants With Multiple Myeloma (MM) Following Dosing With Samalizumab | Not Evaluable | 0 Participants |
Secondary
Density Of B-CLL Cells Bound At Baseline (Predose) And Day 1 (Postdose)
Bound samalizumab was detected using a mAb specific for samalizumab. The binding of samalizumab to CD200 on peripheral B-CLL tumor cells was evaluated in participants with B-CLL by flow cytometry and expressed as mean channel fluorescence intensity (MFI) of bound samalizumab to provide an indication of the density of bound samalizumab on target B-CLL cells. For participants with insufficient numbers of peripheral B-CLL for analysis, the samples were documented as unevaluable and an analysis was not performed.
Time frame: Baseline (Predose) and Day 1 (Postdose)
Population: All participants with B-CLL who had evaluable assessments for bound samalizumab were included in the analysis. No participants with B-CLL received samalizumab at the 600 mg/m\^2 dose level.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Samalizumab | Density Of B-CLL Cells Bound At Baseline (Predose) And Day 1 (Postdose) | Baseline (Predose) | 2.95 mean channel fluorescent intensity |
| Samalizumab | Density Of B-CLL Cells Bound At Baseline (Predose) And Day 1 (Postdose) | Day 1 (Postdose) | 3.85 mean channel fluorescent intensity |
| Samalizumab 100 mg/m^2 | Density Of B-CLL Cells Bound At Baseline (Predose) And Day 1 (Postdose) | Day 1 (Postdose) | 7.10 mean channel fluorescent intensity |
| Samalizumab 100 mg/m^2 | Density Of B-CLL Cells Bound At Baseline (Predose) And Day 1 (Postdose) | Baseline (Predose) | 4.10 mean channel fluorescent intensity |
| Samalizumab 200 mg/m^2 | Density Of B-CLL Cells Bound At Baseline (Predose) And Day 1 (Postdose) | Day 1 (Postdose) | 17.95 mean channel fluorescent intensity |
| Samalizumab 200 mg/m^2 | Density Of B-CLL Cells Bound At Baseline (Predose) And Day 1 (Postdose) | Baseline (Predose) | 3.25 mean channel fluorescent intensity |
| Samalizumab 300 mg/m^2 | Density Of B-CLL Cells Bound At Baseline (Predose) And Day 1 (Postdose) | Baseline (Predose) | 2.35 mean channel fluorescent intensity |
| Samalizumab 300 mg/m^2 | Density Of B-CLL Cells Bound At Baseline (Predose) And Day 1 (Postdose) | Day 1 (Postdose) | 11.20 mean channel fluorescent intensity |
| Samalizumab 400 mg/m^2 | Density Of B-CLL Cells Bound At Baseline (Predose) And Day 1 (Postdose) | Day 1 (Postdose) | 5.80 mean channel fluorescent intensity |
| Samalizumab 400 mg/m^2 | Density Of B-CLL Cells Bound At Baseline (Predose) And Day 1 (Postdose) | Baseline (Predose) | 2.40 mean channel fluorescent intensity |
| Samalizumab 500 mg/m^2 | Density Of B-CLL Cells Bound At Baseline (Predose) And Day 1 (Postdose) | Day 1 (Postdose) | 2.30 mean channel fluorescent intensity |
| Samalizumab 500 mg/m^2 | Density Of B-CLL Cells Bound At Baseline (Predose) And Day 1 (Postdose) | Baseline (Predose) | 1.40 mean channel fluorescent intensity |
Secondary
Percent Of Bound Samalizumab On B-Cell Chronic Lymphocytic Leukemia (B-CLL) Cells In Participants With B-CLL At Baseline (Predose) And Day 1 (Postdose)
Bound samalizumab was detected using a monoclonal antibody (mAb) specific for samalizumab. The binding of samalizumab to CD200 on peripheral B-CLL tumor cells was evaluated in participants with B-CLL by flow cytometry and expressed as the percent of B-CLL cells bound by samalizumab. For participants with insufficient numbers of peripheral B-CLL for analysis, the samples were documented as unevaluable and an analysis was not performed.
Time frame: Baseline (Predose) and Day 1 (Postdose)
Population: All participants with B-CLL who had evaluable assessments for bound samalizumab were included in the analysis. No participants with B-CLL received samalizumab at the 600 mg/m\^2 dose level.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Samalizumab | Percent Of Bound Samalizumab On B-Cell Chronic Lymphocytic Leukemia (B-CLL) Cells In Participants With B-CLL At Baseline (Predose) And Day 1 (Postdose) | Baseline (Predose) | 0.60 percentage of B-CLL cells bound |
| Samalizumab | Percent Of Bound Samalizumab On B-Cell Chronic Lymphocytic Leukemia (B-CLL) Cells In Participants With B-CLL At Baseline (Predose) And Day 1 (Postdose) | Day 1 (Postdose) | 2.50 percentage of B-CLL cells bound |
| Samalizumab 100 mg/m^2 | Percent Of Bound Samalizumab On B-Cell Chronic Lymphocytic Leukemia (B-CLL) Cells In Participants With B-CLL At Baseline (Predose) And Day 1 (Postdose) | Baseline (Predose) | 0.80 percentage of B-CLL cells bound |
| Samalizumab 100 mg/m^2 | Percent Of Bound Samalizumab On B-Cell Chronic Lymphocytic Leukemia (B-CLL) Cells In Participants With B-CLL At Baseline (Predose) And Day 1 (Postdose) | Day 1 (Postdose) | 3.90 percentage of B-CLL cells bound |
| Samalizumab 200 mg/m^2 | Percent Of Bound Samalizumab On B-Cell Chronic Lymphocytic Leukemia (B-CLL) Cells In Participants With B-CLL At Baseline (Predose) And Day 1 (Postdose) | Baseline (Predose) | 0.50 percentage of B-CLL cells bound |
| Samalizumab 200 mg/m^2 | Percent Of Bound Samalizumab On B-Cell Chronic Lymphocytic Leukemia (B-CLL) Cells In Participants With B-CLL At Baseline (Predose) And Day 1 (Postdose) | Day 1 (Postdose) | 28.70 percentage of B-CLL cells bound |
| Samalizumab 300 mg/m^2 | Percent Of Bound Samalizumab On B-Cell Chronic Lymphocytic Leukemia (B-CLL) Cells In Participants With B-CLL At Baseline (Predose) And Day 1 (Postdose) | Baseline (Predose) | 0.60 percentage of B-CLL cells bound |
| Samalizumab 300 mg/m^2 | Percent Of Bound Samalizumab On B-Cell Chronic Lymphocytic Leukemia (B-CLL) Cells In Participants With B-CLL At Baseline (Predose) And Day 1 (Postdose) | Day 1 (Postdose) | 16.80 percentage of B-CLL cells bound |
| Samalizumab 400 mg/m^2 | Percent Of Bound Samalizumab On B-Cell Chronic Lymphocytic Leukemia (B-CLL) Cells In Participants With B-CLL At Baseline (Predose) And Day 1 (Postdose) | Baseline (Predose) | 3.20 percentage of B-CLL cells bound |
| Samalizumab 400 mg/m^2 | Percent Of Bound Samalizumab On B-Cell Chronic Lymphocytic Leukemia (B-CLL) Cells In Participants With B-CLL At Baseline (Predose) And Day 1 (Postdose) | Day 1 (Postdose) | 13.50 percentage of B-CLL cells bound |
| Samalizumab 500 mg/m^2 | Percent Of Bound Samalizumab On B-Cell Chronic Lymphocytic Leukemia (B-CLL) Cells In Participants With B-CLL At Baseline (Predose) And Day 1 (Postdose) | Baseline (Predose) | 1.40 percentage of B-CLL cells bound |
| Samalizumab 500 mg/m^2 | Percent Of Bound Samalizumab On B-Cell Chronic Lymphocytic Leukemia (B-CLL) Cells In Participants With B-CLL At Baseline (Predose) And Day 1 (Postdose) | Day 1 (Postdose) | 3.40 percentage of B-CLL cells bound |