Safety and Dose Ranging Study of Samalizumab to Treat Relapsing or Refractory CLL or MM

Alexion Pharmaceuticals

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Multiple Myeloma; B-cell Chronic Lymphocytic Leukemia

Treatments: Drug: Samalizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT00648739

C07-003

Details and patient eligibility

About

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.

Full 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.

Enrollment: 26 patients

Sex: All

Volunteers: No Healthy Volunteers

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

Trial design

26 participants in 1 patient group

Samalizumab

Experimental group

Description:

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. If no participants enrolled into a cohort experienced a DLT, escalation to the next dose level occurred with a new cohort. If any 1 of the initial 3 participants in the cohort experienced a DLT, the cohort was expanded to at least 6 participants. Then, if less than one third of participants within the cohort experienced a DLT, escalation to the next dose level occurred with a new cohort. Dose cohorts were enrolled sequentially.

Treatment:

Drug: Samalizumab