Study of Natalizumab in Relapsed/Refractory Multiple Myeloma

NCT00675428 | Terminated Phase 1 Results DMC

• 1 other identifier: 101MY201
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

The primary objectives of the study are to evaluate the safety profile and the anti-tumor activity of 2 dose levels of natalizumab in participants with relapsed or refractory multiple myeloma. Secondary objectives are to assess the pharmacokinetic (PK) profile of natalizumab in this study population and to assess peripheral blood mononuclear cell (PBMC) saturation of very late antigen-4 (VLA-4, an α4-integrin) and evaluate possible correlations with clinical activity.

Conditions

Multiple Myeloma

Keywords

Relapsed or refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Dose Limiting Toxicities (DLTs)

  DLTs = any ≥grade 3 toxicity related to treatment; treatment delays of ≥7 days due to any toxicity related to treatment, with the exception of hepatic transaminases; or alanine and/or aspartate aminotransferase (ALT and/or AST) \>3\*upper limit of normal (ULN) with either a total bilirubin \>2\*ULN or an international normalized ratio (INR) \>1.5 related to treatment, or with the appearance of worsening fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, or eosinophilia.

  Day 1 up to Day 28

• Objective Response Rate (ORR)

  Response rates were classified according to the International Uniform Response Criteria for Multiple Myeloma (Durie et al, 2006).

  Day 1 up to Month 6

• Number of Participants With Adverse Events (AEs)

  An AE was defined as any untoward medical occurrence in a participant administered medicinal (investigational) product and that does not necessarily have a causal relationship with this product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. See the adverse events section of the record for more details.

  Day 1 up to Month 6

Secondary Outcomes (4)

• Number Of Participants Who Achieve A Complete Response

  Day 1 up to Month 6

• Kaplan-Meier Estimates for Duration Of Response For Participants With A Response

  Day 1 up to Month 6

• Pharmacokinetic (PK) Profile Of Natalizumab

  Cycles 1 and 6: Day 1 (before infusion and 0.25, 2, 6 and 24 hours after infusion), Days 8, 15, 22. Cycles 2-5: Day 1 (before infusion and 0.25 hour after infusion)

• Natalizumab Binding Saturation Of α4 Integrin Sites On Peripheral Blood Mononuclear Cells (PBMC)

  Cycle 1: Day 1 (1 hour before infusion and 1 and 24 hours after infusion), Days 8, 15, 22. Cycles 2-5: 1 hour before and 1 hour after infusion). Cycle 6: Day 1 (1 hour before infusion and 1 hour after infusion), Days 8, 15, 22.

Study Arms (2)

Natalizumab 300 mg

EXPERIMENTAL

Intravenous (IV) infusions of natalizumab 300 mg once every 28 days for 6 months.

Drug: BG00002 (natalizumab)

Natalizumab 450 mg

EXPERIMENTAL

Intravenous (IV) infusions of natalizumab 450 mg once every 28 days for 6 months.

Drug: BG00002 (natalizumab)

Interventions

BG00002 (natalizumab) DRUG

Also known as: Tysabri

Natalizumab 300 mg; Natalizumab 450 mg

Eligibility Criteria

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

You may qualify if:

• Relapsed or refractory multiple myeloma that was treated with or was considered inappropriate for treatment with bortezomib and an IMiD® drug (including an analogue).
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2.
• Corrected calcium \<10.6 mg/dL.

You may not qualify if:

• Candidates for stem cell transplantation willing to undergo transplantation. (Subjects who are candidates for stem cell transplantation, but are not willing to undergo transplant will be eligible for the study.)
• Autologous stem cell transplantation \<3 months post-transplant.
• Prior allogeneic stem cell transplantation.
• Nonsecretory myeloma.
• Plasma cell leukemia (\>2000/µL circulating plasma cells by standard cell counting differential), hyperleukocytosis (white blood cells \>100,000/µL), clinical evidence of hyperviscosity syndrome, or polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome (POEMS), or primary systemic amyloidosis.
• Subjects who cannot undergo a brain magnetic resonance imaging (MRI) study.
• Clinically significant (as determined by the Investigator) 12 lead electrocardiogram (ECG) abnormalities, including QTc prolongation (\>450 ms in males, \>470 ms in females).

Sponsors & Collaborators

• Biogen: lead

Study Sites (2)

Research Center

Scottsdale, Arizona, United States

Location

Research Center

Rochester, Minnesota, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

Natalizumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; 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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Biogen Idec Study Medical Director
• Organization: Biogen Idec

clinicaltrials@biogenidec.com

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2008
• First Posted: May 9, 2008
• Study Start: September 1, 2008
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: September 19, 2014
• Results First Posted: September 19, 2014

Record last verified: 2014-09

Locations

US (2)