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

NCT01248455 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 11002411-C-0024
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Myeloma; Myeloma; Smoldering Multiple Myeloma

Keywords

Monoclonal Antibody; NK Cell Mediated Killing; Response Rate; Pharmacokinetics; Biological Activity; Smoldering Multiple Myeloma; SMM

Outcome Measures

Primary Outcomes (1)

• Response Rate

  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.

  1 year

Secondary Outcomes (1)

• Count of Participants With Serious and Non-Serious Adverse Events

  Date treatment consent signed to date off study, approximately 3 years and 5 months

Study Arms (1)

anti-KIR in Smoldering Multiple Myeloma Patients

EXPERIMENTAL

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

Drug: (Anti-KIR)

Interventions

(Anti-KIR) DRUG

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

anti-KIR in Smoldering Multiple Myeloma Patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of smoldering multiple myeloma (SMM) will be made in accordance with the clinical diagnostic criteria set forth by the International Myeloma Working Group. These criteria include:
• Serum M-protein greater than or equal to 3 g/dl and/or bone marrow plasma cells greater than or equal to 10 percent
• Absence of anemia: Hemoglobin greater than or equal to 10 g/dl
• Absence of renal failure: calculated creatinine clearance (according to modification of diet in renal disease (MDRD)) greater than or equal to 40 ml/min (or alternatively based on standard creatinine level criteria of 2 mg/dl)
• Absence of hypercalcemia: Calcium less than or equal to 10.5 mg/dl
• Absence of lytic bone lesion (skeletal survey)
• The diagnoses will be confirmed by serum/urine protein electrophoresis, immunofixation and light-chain assays; as well as immunohistochemical analyses of the bone marrow biopsy.
• Age greater than or equal to 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Male or female patient who accepts and is able to use recognized effective contraception (oral contraceptives, intrauterine contraceptive device (IUCD), barrier method of contraception in conjunction with spermicidal jelly) through the study and for four months following the final dose of study drug when relevant.
• The patient must be competent to sign an informed consent form.

You may not qualify if:

• Patients with a diagnosis of multiple myeloma (MM) or a clinical suspicion of an ongoing progression into full-blown MM
• Patients without measurable disease defined as serum monoclonal protein (M-protein) less than 1 g/dL.
• Previous treatment having a proven or potential impact on myeloma cell proliferation or survival (including conventional chemotherapies, immunomodulatory drugs (IMiDs), or proteasome inhibitors).
• Use of any investigational agent within the last 3 months.
• Clinical laboratory values at screening:
• Platelet levels less than 75 times 10\^9/L
• Absolute neutrophil count (ANC) levels less than 1 times 10\^9/L
• Bilirubin levels greater than 1.5 upper limit of normal (ULN) ; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) greater than 3.0 ULN (grade 1 National Cancer Institute (NCI))
• Primary or associated amyloidosis
• Known abnormal cardiac status with any of the following:
• New York Heart Association (NYHA) stage III or IV congestive heart failure
• Myocardial infarction within the previous 6 months
• Symptomatic and/or treatment-refractory cardiac arrhythmia. Patients with controlled or asymptomatic arrhythmia are not excluded from this study.
• Current active infectious disease or positive serology for:
• Human Immunodeficiency Virus (HIV)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Anderson KC, Kyle RA, Rajkumar SV, Stewart AK, Weber D, Richardson P; ASH/FDA Panel on Clinical Endpoints in Multiple Myeloma. Clinically relevant end points and new drug approvals for myeloma. Leukemia. 2008 Feb;22(2):231-9. doi: 10.1038/sj.leu.2405016. Epub 2007 Nov 1.

  PMID: 17972944 BACKGROUND

• Kristinsson SY, Landgren O, Dickman PW, Derolf AR, Bjorkholm M. Patterns of survival in multiple myeloma: a population-based study of patients diagnosed in Sweden from 1973 to 2003. J Clin Oncol. 2007 May 20;25(15):1993-9. doi: 10.1200/JCO.2006.09.0100. Epub 2007 Apr 9.

  PMID: 17420512 BACKGROUND

• Landgren O, Kyle RA, Pfeiffer RM, Katzmann JA, Caporaso NE, Hayes RB, Dispenzieri A, Kumar S, Clark RJ, Baris D, Hoover R, Rajkumar SV. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood. 2009 May 28;113(22):5412-7. doi: 10.1182/blood-2008-12-194241. Epub 2009 Jan 29.

  PMID: 19179464 BACKGROUND

• Korde N, Carlsten M, Lee MJ, Minter A, Tan E, Kwok M, Manasanch E, Bhutani M, Tageja N, Roschewski M, Zingone A, Costello R, Mulquin M, Zuchlinski D, Maric I, Calvo KR, Braylan R, Tembhare P, Yuan C, Stetler-Stevenson M, Trepel J, Childs R, Landgren O. A phase II trial of pan-KIR2D blockade with IPH2101 in smoldering multiple myeloma. Haematologica. 2014 Jun;99(6):e81-3. doi: 10.3324/haematol.2013.103085. Epub 2014 Mar 21. No abstract available.

  PMID: 24658821 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell; Smoldering Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Precancerous Conditions; Hypergammaglobulinemia

Limitations and Caveats

Study stopped after the first stage due to lack of patients meeting the defined primary objective (50% decline in M-protein). The study did not continue to the second stage of enrollment due to lack of efficacy as defined by our criteria.

Results Point of Contact

• Title: Dr. Dickran Kazandijian
• Organization: National Cancer Institute

kazandjiandg@mail.nih.gov

301-480-0532

Study Officials

• Mark J Roschewski, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 24, 2010
• First Posted: November 25, 2010
• Study Start: November 1, 2010
• Primary Completion: May 1, 2014
• Study Completion: April 1, 2015
• Last Updated: November 19, 2019
• Results First Posted: May 15, 2015

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)