Trial Outcomes & Findings for Obatoclax and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma (NCT NCT00719901)

NCT ID: NCT00719901

Last Updated: 2015-01-12

Results Overview

DLT was defined as any events that is determined to be possibly, probably, or definitely related to the combination of bortezomib and GX15-070 (as determined by the investigator) and occurring during the first cycle of treatment, irrespective of whether the toxicity resolved. Hematologic DLT measures were assessed using the continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization via Common Terminology Criteria for Adverse Events (CTCAE) version 3 standard toxicity grading.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

11 participants

Primary outcome timeframe

Up to 21 days of every first course

Results posted on

2015-01-12

Participant Flow

Participants were recruited from 5 medical clinics in the United States between February 2008 and January 2011.

This was a phase I/II trial. A total of 11 participants were accrued, all to the phase I portion. This trial was terminated due to slow accrual and the drug supply of Obatoclax during the phase I; therefore, the phase II portion will never open. No results from the phase II portion are available.

Participant milestones

Participant milestones
Measure
Treatment (Enzyme Inhibitor Therapy)
Patients receive obatoclax mesylate IV over 3 hours and bortezomib (1.3 mg/m\^2) IV on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Study
STARTED
11
Overall Study
COMPLETED
0
Overall Study
NOT COMPLETED
11

Reasons for withdrawal

Reasons for withdrawal
Measure
Treatment (Enzyme Inhibitor Therapy)
Patients receive obatoclax mesylate IV over 3 hours and bortezomib (1.3 mg/m\^2) IV on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Study
Adverse Event
5
Overall Study
Withdrawal by Subject
1
Overall Study
Alternate Treatment
1
Overall Study
Disease Progression
3
Overall Study
Availability of Study Drug
1

Baseline Characteristics

Obatoclax and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Treatment (Enzyme Inhibitor Therapy)
n=10 Participants
Patients receive obatoclax mesylate IV over 3 hours and bortezomib (1.3 mg/m\^2) IV on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Age, Continuous
62.1 years
STANDARD_DEVIATION 10.4 • n=5 Participants
Sex: Female, Male
Female
4 Participants
n=5 Participants
Sex: Female, Male
Male
6 Participants
n=5 Participants
Region of Enrollment
United States
10 participants
n=5 Participants
Performance Status
0=Fully active
1 participants
n=5 Participants
Performance Status
1=Restricted in physically strenuous activity
9 participants
n=5 Participants
Dose Level
Obatoclax mesylate IV 14 mg/m^2
3 participants
n=5 Participants
Dose Level
Obatoclax mesylate IV 30 mg/m^2
4 participants
n=5 Participants
Dose Level
Obatoclax mesylate IV 40 mg/m^2
3 participants
n=5 Participants

PRIMARY outcome

Timeframe: Up to 21 days of every first course

DLT was defined as any events that is determined to be possibly, probably, or definitely related to the combination of bortezomib and GX15-070 (as determined by the investigator) and occurring during the first cycle of treatment, irrespective of whether the toxicity resolved. Hematologic DLT measures were assessed using the continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization via Common Terminology Criteria for Adverse Events (CTCAE) version 3 standard toxicity grading.

Outcome measures

Outcome measures
Measure
Treatment (Enzyme Inhibitor Therapy)
n=10 Participants
Patients receive obatoclax mesylate IV over 3 hours and bortezomib (1.3 mg/m\^2) IV on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Number of Dose-limiting Toxicity (DLT) Incidents (Phase I)
4 Toxicity Incidents

PRIMARY outcome

Timeframe: From baseline to up to 3 years

Population: No participants proceeded to Phase II for evaluation.

In order to be classified as a hematologic response, confirmation of serum monoclonal protein, serum immunoglobulin free light chain (when primary determinant of response) and urine monoclonal protein (when primary determinant of response) results must be made by verification on two consecutive determinations.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From baseline to up to 3 years

In order to be classified as a hematologic response, confirmation of serum monoclonal protein, serum immunoglobulin free light chain (when primary determinant of response) and urine monoclonal protein (when primary determinant of response) results must be made by verification on two consecutive determinations.

Outcome measures

Outcome measures
Measure
Treatment (Enzyme Inhibitor Therapy)
n=10 Participants
Patients receive obatoclax mesylate IV over 3 hours and bortezomib (1.3 mg/m\^2) IV on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Number of Patients Who Have at Least a Partial Response (Phase I)
4 participants

SECONDARY outcome

Timeframe: Time from registration to the time of progression

Population: No participants proceeded to Phase II for evaluation.

The distribution of time to progression will be estimated using the method of Kaplan-Meier.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Time from registration to death due to any cause

Population: No participants proceeded to Phase II for evaluation.

The distribution of overall survival will be estimated using the method of Kaplan-Meier.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Time from study entry to the date patients end treatment

Population: No participants proceeded to Phase II for evaluation.

Time to treatment failure will be evaluated using the method of Kaplan-Meier.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From baseline to up to 3 years

Population: No participants proceeded to Phase II for evaluation.

Toxicity is defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. In addition, we will review all toxicities data that is graded as 3, 4, or 5 and classified as either "unrelated or unlikely to be related" to study treatment in the event of an actual relationship developing. Adverse events and toxicities will be evaluated using all patients who have received any study treatment.

Outcome measures

Outcome data not reported

Adverse Events

Treatment (Enzyme Inhibitor Therapy)

Serious events: 3 serious events
Other events: 10 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Treatment (Enzyme Inhibitor Therapy)
n=10 participants at risk
Patients receive obatoclax mesylate IV over 3 hours and bortezomib (1.3 mg/m\^2) IV on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Investigations
Neutrophil count decreased
20.0%
2/10 • Number of events 2
Nervous system disorders
Depressed level of consciousness
10.0%
1/10 • Number of events 1

Other adverse events

Other adverse events
Measure
Treatment (Enzyme Inhibitor Therapy)
n=10 participants at risk
Patients receive obatoclax mesylate IV over 3 hours and bortezomib (1.3 mg/m\^2) IV on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders
Hemoglobin decreased
100.0%
10/10 • Number of events 36
Cardiac disorders
Cardiac disorder
10.0%
1/10 • Number of events 1
Eye disorders
Diplopia
10.0%
1/10 • Number of events 1
Gastrointestinal disorders
Constipation
20.0%
2/10 • Number of events 2
Gastrointestinal disorders
Diarrhea
70.0%
7/10 • Number of events 12
Gastrointestinal disorders
Nausea
40.0%
4/10 • Number of events 7
Gastrointestinal disorders
Vomiting
20.0%
2/10 • Number of events 3
General disorders
Fatigue
50.0%
5/10 • Number of events 6
Immune system disorders
Hypersensitivity
10.0%
1/10 • Number of events 1
Investigations
Leukocyte count decreased
90.0%
9/10 • Number of events 27
Investigations
Lymphocyte count decreased
40.0%
4/10 • Number of events 4
Investigations
Neutrophil count decreased
80.0%
8/10 • Number of events 26
Investigations
Platelet count decreased
80.0%
8/10 • Number of events 23
Metabolism and nutrition disorders
Anorexia
20.0%
2/10 • Number of events 2
Musculoskeletal and connective tissue disorders
Myalgia
40.0%
4/10 • Number of events 10
Nervous system disorders
Ataxia
10.0%
1/10 • Number of events 1
Nervous system disorders
Depressed level of consciousness
10.0%
1/10 • Number of events 1
Nervous system disorders
Dizziness
10.0%
1/10 • Number of events 1
Nervous system disorders
Extrapyramidal disorder
10.0%
1/10 • Number of events 1
Nervous system disorders
Headache
60.0%
6/10 • Number of events 9
Nervous system disorders
Peripheral motor neuropathy
20.0%
2/10 • Number of events 6
Nervous system disorders
Peripheral sensory neuropathy
70.0%
7/10 • Number of events 27
Nervous system disorders
Speech disorder
10.0%
1/10 • Number of events 1
Psychiatric disorders
Anxiety
20.0%
2/10 • Number of events 4
Psychiatric disorders
Depression
10.0%
1/10 • Number of events 2
Psychiatric disorders
Euphoria
40.0%
4/10 • Number of events 6
Psychiatric disorders
Psychosis
30.0%
3/10 • Number of events 3
Respiratory, thoracic and mediastinal disorders
Dyspnea
80.0%
8/10 • Number of events 15
Respiratory, thoracic and mediastinal disorders
Hypoxia
10.0%
1/10 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Pulmonary fibrosis
10.0%
1/10 • Number of events 1
Skin and subcutaneous tissue disorders
Rash desquamating
20.0%
2/10 • Number of events 2

Additional Information

A. Keith Stewart

Mayo Clinic

Phone: 480-301-4411

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: LTE60