Trial Outcomes & Findings for Dinaciclib in Treating Patients With Relapsed or Refractory Multiple Myeloma (NCT NCT01096342)

NCT ID: NCT01096342

Last Updated: 2014-06-18

Results Overview

Complete Response (CR): Negative immunofixation of serum and urine Normalization of FLC ratio \< 5% plasma cells in bone marrow Disappearance of any soft tissue plasmacytomas Stringent Complete Response (sCR): CR, as above, with absence of clonal cells in bone marrow Partial Response (PR): One of the following: 1. A ≥ 50% reduction of measurable serum M-protein. 2. A reduction in 24h measurable urinary M-protein by ≥ 90% or to \<200 mg per 24h. 3. A ≥ 50% decrease in the difference between involved and uninvolved FLC levels. 4. ≥50% reduction in bone marrow plasma cells is required in place of Mprotein, provided baseline percentage was ≥ 30% 5. A ≥50% reduction in the size of soft tissue plasmacytomas. Very Good Partial Response (VGPR): PR as defined above in addition to having serum and urine M-component detectable by immunofixation but not on electrophoresis.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

16 participants

Primary outcome timeframe

Up to 3 years

Results posted on

2014-06-18

Participant Flow

From 7/2009 to 12/2011, 29 participants were accrued. The study opened at 50 mg/m\^2, accrued 2, and closed for safety review and protocol amendment. The study reopened with a dose escalation phase and accrued 4 at 30 mg/m\^2 dose, 7 at 40 mg/m\^2 dose, and 6 at 50 mg/m\^2 dose. The Phase II dose level was set at 50 mg/m\^2 and accrued 10 participants.

Of the 10 participants accrued in the Phase II portion of the study, one was excluded for protocol violation. The 6 participants treated in the Safety Analysis Phase at the 50 mg/m\^2 dose level (after the protocol amendment) are included in the Phase II analysis. Therefore, this Phase II analysis is based on 15 evaluable participants.

Participant milestones

Participant milestones
Measure
Phase II: 50 mg/m^2
Participants were accrued at 50 mg/m\^2 dose level after December 30, 2009 addendum. Participants to receive 50 mg/m\^2 dinaciclib IV over 2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Study
STARTED
16
Overall Study
COMPLETED
15
Overall Study
NOT COMPLETED
1

Reasons for withdrawal

Reasons for withdrawal
Measure
Phase II: 50 mg/m^2
Participants were accrued at 50 mg/m\^2 dose level after December 30, 2009 addendum. Participants to receive 50 mg/m\^2 dinaciclib IV over 2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Study
Protocol Violation
1

Baseline Characteristics

Dinaciclib in Treating Patients With Relapsed or Refractory Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Phase II
n=15 Participants
Participants were accrued at 50 mg/m\^2 dose level after December 30, 2009 addendum. Participants to receive 50 mg/m\^2 dinaciclib IV over 2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Age, Continuous
64 years
n=99 Participants
Sex: Female, Male
Female
8 Participants
n=99 Participants
Sex: Female, Male
Male
7 Participants
n=99 Participants
Region of Enrollment
United States
12 participants
n=99 Participants
Region of Enrollment
Singapore
3 participants
n=99 Participants

PRIMARY outcome

Timeframe: Up to 3 years

Population: Fifteen of the 16 accrued Phase II participants were analyzed (1 participant was a protocol violation).

Complete Response (CR): Negative immunofixation of serum and urine Normalization of FLC ratio \< 5% plasma cells in bone marrow Disappearance of any soft tissue plasmacytomas Stringent Complete Response (sCR): CR, as above, with absence of clonal cells in bone marrow Partial Response (PR): One of the following: 1. A ≥ 50% reduction of measurable serum M-protein. 2. A reduction in 24h measurable urinary M-protein by ≥ 90% or to \<200 mg per 24h. 3. A ≥ 50% decrease in the difference between involved and uninvolved FLC levels. 4. ≥50% reduction in bone marrow plasma cells is required in place of Mprotein, provided baseline percentage was ≥ 30% 5. A ≥50% reduction in the size of soft tissue plasmacytomas. Very Good Partial Response (VGPR): PR as defined above in addition to having serum and urine M-component detectable by immunofixation but not on electrophoresis.

Outcome measures

Outcome measures
Measure
Phase II
n=15 Participants
Participants were accrued at 50 mg/m\^2 dose level after December 30, 2009 addendum. Participants to receive 50 mg/m\^2 dinaciclib IV over 2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Number of Confirmed Responses, Defined to be an sCR, CR, VGPR, or PR Noted as the Objective Status on Two Consecutive Evaluations.
Complete Response (CR)
0 participants
Number of Confirmed Responses, Defined to be an sCR, CR, VGPR, or PR Noted as the Objective Status on Two Consecutive Evaluations.
Stringent Complete Response (sCR)
0 participants
Number of Confirmed Responses, Defined to be an sCR, CR, VGPR, or PR Noted as the Objective Status on Two Consecutive Evaluations.
Very Good Partial Response (VGPR)
0 participants
Number of Confirmed Responses, Defined to be an sCR, CR, VGPR, or PR Noted as the Objective Status on Two Consecutive Evaluations.
Partial Response (PR)
0 participants

SECONDARY outcome

Timeframe: Time from registration to progression or death due to any cause, assessed up to 3 years

Population: All 15 evaluable participants were analyzed for Progression-Free Survival.

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

Outcome measures

Outcome measures
Measure
Phase II
n=15 Participants
Participants were accrued at 50 mg/m\^2 dose level after December 30, 2009 addendum. Participants to receive 50 mg/m\^2 dinaciclib IV over 2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Progression-free Survival
2.73 months
Interval 0.69 to 5.52

SECONDARY outcome

Timeframe: Date at which the patient's objective status is first noted to be either an sCR, CR, PR, or VGPR to the earliest date progression is documented, assessed up to 3 years

Population: Duration of Response was not analyzed due to lack of responses.

The distribution of duration of response will be estimated using the method of Kaplan-Meier.

Outcome measures

Outcome data not reported

Adverse Events

Phase II: 50 mg/m^2

Serious events: 7 serious events
Other events: 15 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Phase II: 50 mg/m^2
n=15 participants at risk
Participants were accrued at 50 mg/m\^2 dose level after December 30, 2009 addendum. Participants to receive 50 mg/m\^2 dinaciclib IV over 2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Eye disorders
Dry eye syndrome
6.7%
1/15 • Number of events 1
Eye disorders
Eye pain
6.7%
1/15 • Number of events 1
Eye disorders
Photophobia
6.7%
1/15 • Number of events 1
Eye disorders
Vision blurred
6.7%
1/15 • Number of events 1
Gastrointestinal disorders
Diarrhea
13.3%
2/15 • Number of events 2
Investigations
Leukocyte count decreased
6.7%
1/15 • Number of events 1
Investigations
Neutrophil count decreased
6.7%
1/15 • Number of events 1
Investigations
Platelet count decreased
13.3%
2/15 • Number of events 2
Respiratory, thoracic and mediastinal disorders
Dyspnea
6.7%
1/15 • Number of events 1

Other adverse events

Other adverse events
Measure
Phase II: 50 mg/m^2
n=15 participants at risk
Participants were accrued at 50 mg/m\^2 dose level after December 30, 2009 addendum. Participants to receive 50 mg/m\^2 dinaciclib IV over 2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders
Hemoglobin decreased
6.7%
1/15 • Number of events 3
Eye disorders
Vision blurred
6.7%
1/15 • Number of events 1
Gastrointestinal disorders
Cheilitis
6.7%
1/15 • Number of events 1
Gastrointestinal disorders
Constipation
6.7%
1/15 • Number of events 2
Gastrointestinal disorders
Diarrhea
80.0%
12/15 • Number of events 28
Gastrointestinal disorders
Nausea
60.0%
9/15 • Number of events 19
Gastrointestinal disorders
Vomiting
40.0%
6/15 • Number of events 8
General disorders
Fatigue
93.3%
14/15 • Number of events 27
General disorders
Fever
20.0%
3/15 • Number of events 3
General disorders
Pain
6.7%
1/15 • Number of events 2
Infections and infestations
Peripheral nerve infection
6.7%
1/15 • Number of events 1
Infections and infestations
Upper respiratory infection
6.7%
1/15 • Number of events 2
Investigations
Alanine aminotransferase increased
33.3%
5/15 • Number of events 8
Investigations
Aspartate aminotransferase increased
46.7%
7/15 • Number of events 18
Investigations
Bilirubin increased
6.7%
1/15 • Number of events 1
Investigations
Leukocyte count decreased
40.0%
6/15 • Number of events 9
Investigations
Lymphocyte count decreased
33.3%
5/15 • Number of events 10
Investigations
Neutrophil count decreased
26.7%
4/15 • Number of events 5
Investigations
Platelet count decreased
73.3%
11/15 • Number of events 19
Metabolism and nutrition disorders
Anorexia
6.7%
1/15 • Number of events 1
Musculoskeletal and connective tissue disorders
Muscle weakness
6.7%
1/15 • Number of events 3
Nervous system disorders
Peripheral motor neuropathy
13.3%
2/15 • Number of events 11
Nervous system disorders
Peripheral sensory neuropathy
40.0%
6/15 • Number of events 19
Respiratory, thoracic and mediastinal disorders
Dyspnea
13.3%
2/15 • Number of events 2
Skin and subcutaneous tissue disorders
Pruritus
33.3%
5/15 • Number of events 6
Vascular disorders
Hypotension
20.0%
3/15 • Number of events 4

Additional Information

Shaji Kumar, M.D.

Mayo Clinic Cancer Center

Results disclosure agreements

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

Restriction type: LTE60