Clinical trial NCT00675428: Study of Natalizumab in Relapsed/Refractory Multiple Myeloma
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: Relapsed or refractory Multiple Myeloma
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2008-05-09
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Day 1 up to Day 28
measure: Objective Response Rate (ORR)
timeFrame: Day 1 up to Month 6
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Day 1 up to Month 6
Secondary outcomes:
measure: Number Of Participants Who Achieve A Complete Response
timeFrame: Day 1 up to Month 6
measure: Kaplan-Meier Estimates for Duration Of Response For Participants With A Response
timeFrame: Day 1 up to Month 6
measure: Pharmacokinetic (PK) Profile Of Natalizumab
timeFrame: 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)
measure: Natalizumab Binding Saturation Of α4 Integrin Sites On Peripheral Blood Mononuclear Cells (PBMC)
timeFrame: 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.
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Research Center
state: Arizona
city: Rochester
country: United States
facility: Research Center
state: Minnesota
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: