Trial Outcomes & Findings for Study of Natalizumab in Relapsed/Refractory Multiple Myeloma (NCT NCT00675428)

NCT ID: NCT00675428

Last Updated: 2014-09-19

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

6 participants

Primary outcome timeframe

Day 1 up to Day 28

Results posted on

2014-09-19

Participant Flow

This record includes data up to and including the last data values collected during long-term follow-up (27 January 2010).

Participant milestones

Participant milestones
Measure
Natalizumab 300 mg
Intravenous (IV) infusions of natalizumab 300 mg once every 28 days for 6 months.
Natalizumab 450 mg
Intravenous (IV) infusions of natalizumab 450 mg once every 28 days for 6 months.
Overall Study
STARTED
3
3
Overall Study
COMPLETED
0
0
Overall Study
NOT COMPLETED
3
3

Reasons for withdrawal

Reasons for withdrawal
Measure
Natalizumab 300 mg
Intravenous (IV) infusions of natalizumab 300 mg once every 28 days for 6 months.
Natalizumab 450 mg
Intravenous (IV) infusions of natalizumab 450 mg once every 28 days for 6 months.
Overall Study
Disease Progression
2
2
Overall Study
No Disease Response After Cycle 6
0
1
Overall Study
Physician Decision
1
0

Baseline Characteristics

Study of Natalizumab in Relapsed/Refractory Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Natalizumab 300 mg
n=3 Participants
Intravenous (IV) infusions of natalizumab 300 mg once every 28 days for 6 months.
Natalizumab 450 mg
n=3 Participants
Intravenous (IV) infusions of natalizumab 450 mg once every 28 days for 6 months.
Total
n=6 Participants
Total of all reporting groups
Age, Continuous
67.0 years
n=5 Participants
68.0 years
n=7 Participants
67.5 years
n=5 Participants
Sex: Female, Male
Female
2 Participants
n=5 Participants
1 Participants
n=7 Participants
3 Participants
n=5 Participants
Sex: Female, Male
Male
1 Participants
n=5 Participants
2 Participants
n=7 Participants
3 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Natalizumab 300 mg
n=3 Participants
Intravenous (IV) infusions of natalizumab 300 mg once every 28 days for 6 months.
Natalizumab 450 mg
n=3 Participants
Intravenous (IV) infusions of natalizumab 450 mg once every 28 days for 6 months.
Number of Participants With Dose Limiting Toxicities (DLTs)
0 participants
0 participants

PRIMARY outcome

Timeframe: Day 1 up to Month 6

Population: ORR was not calculated because the study was terminated early.

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

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Natalizumab 300 mg
n=3 Participants
Intravenous (IV) infusions of natalizumab 300 mg once every 28 days for 6 months.
Natalizumab 450 mg
n=3 Participants
Intravenous (IV) infusions of natalizumab 450 mg once every 28 days for 6 months.
Number of Participants With Adverse Events (AEs)
3 participants
3 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Natalizumab 300 mg
n=3 Participants
Intravenous (IV) infusions of natalizumab 300 mg once every 28 days for 6 months.
Natalizumab 450 mg
n=3 Participants
Intravenous (IV) infusions of natalizumab 450 mg once every 28 days for 6 months.
Number Of Participants Who Achieve A Complete Response
0 participants
0 participants

SECONDARY outcome

Timeframe: Day 1 up to Month 6

Population: Duration of response was not calculated because the study was terminated early.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

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)

Population: PK analysis was not performed because the study was terminated early.

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

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.

Population: Analysis of binding saturation of α4 integrin sites was not performed because the study was terminated early.

Outcome measures

Outcome data not reported

Adverse Events

Natalizumab 300 mg

Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths

Natalizumab 450 mg

Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Natalizumab 300 mg
n=3 participants at risk
Intravenous (IV) infusions of natalizumab 300 mg once every 28 days for 6 months.
Natalizumab 450 mg
n=3 participants at risk
Intravenous (IV) infusions of natalizumab 450 mg once every 28 days for 6 months.
Infections and infestations
Pneumonia
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Renal and urinary disorders
Acute Renal Failure
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).

Other adverse events

Other adverse events
Measure
Natalizumab 300 mg
n=3 participants at risk
Intravenous (IV) infusions of natalizumab 300 mg once every 28 days for 6 months.
Natalizumab 450 mg
n=3 participants at risk
Intravenous (IV) infusions of natalizumab 450 mg once every 28 days for 6 months.
Infections and infestations
Pneumonia
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Infections and infestations
Respiratory Tract Infection
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Blood and lymphatic system disorders
Anaemia
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Blood and lymphatic system disorders
Lymphopenia
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Blood and lymphatic system disorders
Neutropenia
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Blood and lymphatic system disorders
Thrombocytopenia
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Metabolism and nutrition disorders
Dehydration
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Metabolism and nutrition disorders
Hypercalcaemia
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Metabolism and nutrition disorders
Hypokalaemia
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Metabolism and nutrition disorders
Hyponatraemia
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Psychiatric disorders
Confusional State
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Respiratory, thoracic and mediastinal disorders
Dyspnoea
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Gastrointestinal disorders
Constipation
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Gastrointestinal disorders
Nausea
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Musculoskeletal and connective tissue disorders
Arthralgia
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Musculoskeletal and connective tissue disorders
Neck Pain
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
General disorders
Fatigue
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Investigations
Blood Creatinine Increased
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Infections and infestations
Staphylococcal Infection
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Infections and infestations
Upper Respiratory Tract Infection
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Blood and lymphatic system disorders
Leukopenia
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Metabolism and nutrition disorders
Decreased Appetite
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Nervous system disorders
Neuropathy Peripheral
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Respiratory, thoracic and mediastinal disorders
Epistaxis
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Renal and urinary disorders
Renal Failure Acute
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
Investigations
Aspartate Aminotransferase Increased
0.00%
0/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
33.3%
1/3 • 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).

Additional Information

Biogen Idec Study Medical Director

Biogen Idec

Results disclosure agreements

  • Principal investigator is a sponsor employee Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
  • Publication restrictions are in place

Restriction type: OTHER