A Phase II Trial of Anti-KIR in Smoldering Multiple Myeloma

Phase 2

Terminated

Conditions: Myeloma
Multiple Myeloma
Smoldering Multiple Myeloma

Interventions: Drug: (Anti-KIR)

Registration Number: NCT01248455

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: Background:

* Recent studies have shown that smoldering multiple myeloma has a high risk of progressing to multiple myeloma, an aggressive type of bone marrow cancer, within 5 years of diagnosis. People with smoldering multiple myeloma have abnormal blood test results that show a high level of monoclonal protein (M-protein) in the blood and of plasma cells in the bone marrow. There are currently no known effective treatments to prevent smoldering multiple myeloma from developing into multiple myeloma, and there are no known tests for determining whether an individual with smoldering multiple myeloma will develop multiple myeloma.

* Certain cells in the immune system, known as natural killer (NK) cells, are active against multiple myeloma. The experimental drug anti-killer cell immunoglobulin-like receptor (anti-KIR) has been shown to help NK cells kill multiple myeloma cells. Researchers are interested in determining whether anti-KIR can be given to individuals with smoldering multiple myeloma to improve their abnormal blood test results.

Objectives:

- To evaluate the safety and effectiveness of anti-KIR as a treatment for abnormal blood test results related to smoldering multiple myeloma.

Eligibility:

- Individuals at least 18 years of age who have been diagnosed with smoldering multiple myeloma.

Design:

* Participants will be screened with a physical examination and medical history, and will provide baseline blood, urine, and bone marrow samples before beginning the study drug.

* Participants will receive anti-KIR intravenously for 1 hour, and will be closely monitored for 24 hours after receiving the first dose. If there are no serious side effects, participants will receive five additional anti-KIR doses, one every other month, for a total of six treatment cycles.

* Participants will have monthly visits to provide additional blood and urine samples, and may have additional bone marrow biopsies as directed by the study researchers.

* Participants will have followup visits every 3 to 6 months for up to 5 years after receiving anti-KIR treatment.

Detailed Description: Background:

* Multiple myeloma (MM) is an incurable plasma cell neoplasm with a median survival of 3-4 years.

* Smoldering multiple myeloma (SMM) is a premalignant plasma cell disorder characterized by monoclonal protein greater than or equal to 3 g/dL or bone marrow plasma cells greater than or equal to 10 percent in the absence of myeloma-related tissue impairment with 51 percent progression to MM at 5 years.

* Current recommendations do not endorse treatment of SMM with chemotherapy.

* Transplanted Natural Killer (NK) Cells have anti-myeloma activity.

* Anti-KIR (IPH2101) is a monoclonal antibody that facilitates NK cell mediated killing of myeloma cells by blocking inhibitory receptors (KIR) on NK cells.

Objectives:

* To assess the response rate of anti-KIR(IPH2101) in patients with SMM

* To evaluate the toxicity of anti-KIR(IPH2101) in patients with SMM

* To evaluate the pharmacokinetic parameters and biological activity of anti-KIR (IPH2101)

Eligibility:

* A confirmed diagnosis of SMM

* Age greater than or equal to 18 years

* Eastern Cooperative Oncology Group (ECOG) performance status in the range of 0-1.

* Without serious co-morbidity that would interfere with receipt of anti-KIR(IPH2101)

Design:

* Single-arm Phase II trial of anti-KIR(IPH2101) for patients with SMM.

* All patients will have initial evaluation and confirmation of diagnosis.

* Patients will receive anti-KIR(IPH2101) (1mg/kg) every other month for 6 cycles.

* Patients will have routine blood work with serum protein electrophoresis (SPEP) and immunofixation monthly.

* Pre- and post-treatment bone marrow biopsies will be obtained for confirmation of diagnosis and correlative studies.

* Patients may donate cellular products or tissues as appropriate for research purposes.

* Optimal two-stage phase II design will be employed, initially enrolling 9 patients. If 3 or more have a positive outcome, then a total of 21 patients will be enrolled in this study.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 9

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
anti-KIR in Smoldering Multiple Myeloma Patients	(Anti-KIR)	Patients will receive anti-KIR(IPH2101) (1mg/kg) every other month for 6 cycles

Primary Outcome Measures

Name	Time	Method
Response Rate	1 year	Response rate is defined as the percentage of participants with a 50% decline in monoclonal protein (M-protein) assessed by the International Multiple Myeloma Working Group (IMWG) for multiple myeloma (MM) criteria. Minimal response (MR) is MR \>25% and \<50% decrease in M-protein. Biochemical progression (BP) is asymptomatic, ≥ 25% M-protein increase from baseline and an absolute increase of M-protein of 0.75 g/dL demonstrated on two separate occasions. Progressive disease (PD), (clinical progression to symptomatic MM) is development of CRAB (hyperCalcemia (corrected calcium \>2.75 mmol/L), Renal insufficiency (attributed to MM), Anemia (hemoglobin \<10g/dL), and Bone lesions (lytic lesions or osteoporosis with compression fractures) criteria end organ damage. Stable disease (SD) is not meeting the criteria for minimal response, biochemical progression and progressive disease.

Secondary Outcome Measures

Name	Time	Method
Count of Participants With Serious and Non-Serious Adverse Events	Date treatment consent signed to date off study, approximately 3 years and 5 months	Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.