Clinical trial NCT00648739: Safety and Dose Ranging Study of Samalizumab to Treat Relapsing or Refractory CLL or MM
Official title: A Phase I/II Open Label Study To Evaluate The Safety, Pharmacokinetics And Pharmacodynamics Of ALXN6000 In Patients With Relapsing Or Refractory B-Cell Chronic Lymphocytic Leukemia Or Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: B-cell Chronic Lymphocytic Leukemia
Multiple Myeloma
Keywords: B-cell Chronic Lymphocytic Leukemia
Leukemia
Multiple Myeloma
CD200
Anti-CD200
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2008-04-01
Enrollment: 26
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) Of Samalizumab
timeFrame: From first dose through 10 weeks after the last dose
measure: Number Of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From first dose through 10 weeks after the last dose
Secondary outcomes:
measure: 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)
timeFrame: Baseline (Predose) and Day 1 (Postdose)
measure: Density Of B-CLL Cells Bound At Baseline (Predose) And Day 1 (Postdose)
timeFrame: Baseline (Predose) and Day 1 (Postdose)
measure: Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate
timeFrame: From first dose through 10 weeks after the last dose
measure: Clinical Response Of Participants With Multiple Myeloma (MM) Following Dosing With Samalizumab
timeFrame: From first dose through 10 weeks after the last dose
Other outcomes:
Locations:
city: Tucson
country: United States
state: Arizona
city: Atlanta
country: United States
state: Georgia
city: Morristown
country: United States
state: New Jersey
city: Durham
country: United States
state: North Carolina
Study officials:
References:
citation: Mahadevan D, Lanasa MC, Farber C, Pandey M, Whelden M, Faas SJ, Ulery T, Kukreja A, Li L, Bedrosian CL, Zhang X, Heffner LT. Phase I study of samalizumab in chronic lymphocytic leukemia and multiple myeloma: blockade of the immune checkpoint CD200. J Immunother Cancer. 2019 Aug 23;7(1):227. doi: 10.1186/s40425-019-0710-1.