Study of Natalizumab in Relapsed/Refractory Multiple Myeloma

• ClinicalTrials.gov Identifier: NCT00675428
• Recruitment Status: Terminated
• First Posted: May 9, 2008
• Results First Posted: September 19, 2014
• Last Update Posted: September 19, 2014
• Sponsor: Biogen
• Information provided by (Responsible Party): Biogen

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Drug: BG00002 (natalizumab)	Phase 1; Phase 2

Detailed Description:

Despite no protocol-defined study stopping criteria being met, the sponsor decided to terminate enrollment after the phase 1 portion was complete and to not move into the phase 2 portion of the study. This decision was made due to difficulty enrolling participants and was not due to any safety concerns.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 6 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2, Two-Arm, Dose-Finding Study of Natalizumab for the Treatment of Subjects With Relapsed or Refractory Multiple Myeloma
• Study Start Date: September 2008
• Actual Primary Completion Date: December 2009
• Actual Study Completion Date: December 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Natalizumab 300 mg; Intravenous (IV) infusions of natalizumab 300 mg once every 28 days for 6 months.	Drug: BG00002 (natalizumab); Other Name: Tysabri
Experimental: Natalizumab 450 mg; Intravenous (IV) infusions of natalizumab 450 mg once every 28 days for 6 months.	Drug: BG00002 (natalizumab); Other Name: Tysabri

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: Day 1 up to Day 28 ]
   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.
2. Objective Response Rate (ORR) [ Time Frame: Day 1 up to Month 6 ]
   Response rates were classified according to the International Uniform Response Criteria for Multiple Myeloma (Durie et al, 2006).
3. Number of Participants With Adverse Events (AEs) [ Time Frame: Day 1 up to Month 6 ]
   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.

Secondary Outcome Measures :

1. Number Of Participants Who Achieve A Complete Response [ Time Frame: Day 1 up to Month 6 ]
   Response rates were classified according to the International Uniform Response Criteria for Multiple Myeloma (Durie et al, 2006). Complete Response (CR): negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas , and ≤ 5% plasma cells in the bone marrow. Stringent CR (sCR): CR as defined above, and normal free light chain (FLC) ratio, and absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence, based on a κ/λ ratio of > 4:1 or < 1:2 performed on a minimum of 100 plasma cells.
2. Kaplan-Meier Estimates for Duration Of Response For Participants With A Response [ Time Frame: Day 1 up to Month 6 ]
   Response rates were classified according to the International Uniform Response Criteria for Multiple Myeloma (Durie et al, 2006). Kaplan-Meier methods were used to estimate the median duration of response and associated 95% confidence intervals.
3. Pharmacokinetic (PK) Profile Of Natalizumab [ Time Frame: 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) ]
   PK modeling, either compartmental or noncompartmental-based, was used to describe serum concentrations. Standard PK parameters estimated include: area-under-the-concentration-time curve (AUC), maximum-observed concentration (Cmax), time-to-reach maximum concentration (Tmax), total body clearance (Cl), volume of distribution (Vd), and elimination half-life (t1/2).
4. Natalizumab Binding Saturation Of α4 Integrin Sites On Peripheral Blood Mononuclear Cells (PBMC) [ Time Frame: 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. ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

• 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.

Key Exclusion Criteria:

• 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).

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

United States, Arizona

Research Center

Scottsdale, Arizona, United States

United States, Minnesota

Research Center

Rochester, Minnesota, United States

Sponsors and Collaborators

Biogen

Investigators

• Study Director: Medical Director; Biogen

More Information

• Responsible Party: Biogen
• ClinicalTrials.gov Identifier: NCT00675428
• Other Study ID Numbers: 101MY201
• First Posted: May 9, 2008
• Results First Posted: September 19, 2014
• Last Update Posted: September 19, 2014
• Last Verified: September 2014

Keywords provided by Biogen:

Relapsed or refractory Multiple Myeloma

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Natalizumab; Immunologic Factors; Physiological Effects of Drugs