Trial Outcomes & Findings for MDX-010 in Treating Patients With Recurrent or Refractory Lymphoma (NCT NCT00089076)

NCT ID: NCT00089076

Last Updated: 2014-05-30

Results Overview

Confirmed response is at least a 50% decrease in the sum of the products of the greatest diameters (SPD) of the six largest dominant nodes or nodal masses and no increase in the size of other nodes, liver, or spleen and splenic and hepatic nodules must regress by at least 50% in the SPD and no new sites of disease.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

18 participants

Primary outcome timeframe

From registration to month 7

Results posted on

2014-05-30

Participant Flow

Participants were recruited from 2 medical clinics in the United States between August \> 2004 and September 2007.

This was a phase I/II trial. A total of 18 participants were accrued, all to the phase I portion. This trial was terminated due to study design 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
MDX-010
Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) IV over 90 minutes on day 1. Treatment repeats every 28 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.
Overall Study
STARTED
18
Overall Study
COMPLETED
8
Overall Study
NOT COMPLETED
10

Reasons for withdrawal

Reasons for withdrawal
Measure
MDX-010
Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) IV over 90 minutes on day 1. Treatment repeats every 28 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.
Overall Study
Alternate Therapy
1
Overall Study
Withdrawal by Subject
2
Overall Study
Progression
7

Baseline Characteristics

MDX-010 in Treating Patients With Recurrent or Refractory Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
MDX-010
n=18 Participants
Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) IV over 90 minutes on day 1. Treatment repeats every 28 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.
Age, Continuous
56 years
n=5 Participants
Sex: Female, Male
Female
6 Participants
n=5 Participants
Sex: Female, Male
Male
12 Participants
n=5 Participants
Region of Enrollment
United States
18 participants
n=5 Participants
Disease Histology
Follicular grade 1 lymphoma
9 participants
n=5 Participants
Disease Histology
Follicular grade 2 lymphoma
5 participants
n=5 Participants
Disease Histology
Diffuse large B-cell lymphoma
3 participants
n=5 Participants
Disease Histology
Mantle cell lymphoma
1 participants
n=5 Participants
Number of prior treatments
2 Treatments
n=5 Participants
Dose Level
3 mg/kg first dose, then 1 mg/kg monthly x 3 doses
12 participants
n=5 Participants
Dose Level
3 mg/kg monthly x 4 doses
6 participants
n=5 Participants

PRIMARY outcome

Timeframe: From registration to month 7

Confirmed response is at least a 50% decrease in the sum of the products of the greatest diameters (SPD) of the six largest dominant nodes or nodal masses and no increase in the size of other nodes, liver, or spleen and splenic and hepatic nodules must regress by at least 50% in the SPD and no new sites of disease.

Outcome measures

Outcome measures
Measure
MDX-010
n=18 Participants
Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) IV over 90 minutes on day 1. Treatment repeats every 28 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.
Number of Overall Confirmed Responses(Complete Response or Partial Response)
2 participants

SECONDARY outcome

Timeframe: From registration to progression (up to 2 years)

Population: No participants proceeded to Phase 2 for evaluation.

The time to progression is defined as the time from registration to the time of progression. Those who die will be considered to have had disease progression unless documented evidence clearly indicates no progression has occurred. The distribution of time to progression will be estimated using the method of Kaplan-Meier.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From registration to death (up to 2 years)

Population: No participants proceeded to Phase 2 for evaluation.

The overall survival or survival time is defined as the time from registration to death due to any cause. The distribution of overall survival will be estimated using the method of Kaplan-Meier.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From response to progression (up to 2 years)

Population: No participants proceeded to Phase 2 for evaluation.

Duration of response will be calculated from the documentation of confirmed response until the date of progression in the subset of patients who respond.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Before treatment to 1 month after therapy initiation

Population: The analysis population contains patients that had peripheral blood available for analysis from before and 1 month after initiating therapy along with being able to conduct the analysis on the marker. This resulted in the number of participants analyzed being less than the enrolled participants.

Flow cytometric analysis of T-cell surface markers before and 1 month after initiation therapy

Outcome measures

Outcome measures
Measure
MDX-010
n=14 Participants
Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) IV over 90 minutes on day 1. Treatment repeats every 28 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.
Mean Change in % of CD3+CD4+ for Marker HLA-DR+
1.8 percentage of change of CD3+CD4+
Standard Error 1.2

SECONDARY outcome

Timeframe: Before treatment to 1 month after therapy initiation

Population: The analysis population contains patients that had peripheral blood available for analysis from before and 1 month after initiating therapy along with being able to conduct the analysis on the marker. This resulted in the number of participants analyzed being less than the enrolled participants.

Flow cytometric analysis of T-cell surface markers before and 1 month after initiation therapy

Outcome measures

Outcome measures
Measure
MDX-010
n=14 Participants
Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) IV over 90 minutes on day 1. Treatment repeats every 28 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.
Mean Change in % of CD3+CD4- for Marker HLA-DR+
1.9 percentage of change of CD3+CD4-
Standard Error 2.0

SECONDARY outcome

Timeframe: Before treatment to 1 month after therapy initiation

Population: The analysis population contains patients that had peripheral blood available for analysis from before and 1 month after initiating therapy along with being able to conduct the analysis on the marker. This resulted in the number of participants analyzed being less than the enrolled participants.

Flow cytometric analysis of T-cell surface markers before and 1 month after initiation therapy

Outcome measures

Outcome measures
Measure
MDX-010
n=13 Participants
Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) IV over 90 minutes on day 1. Treatment repeats every 28 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.
Mean Change in % of CD3+CD4+ for Marker CD45RO+
5.0 percentage of change of CD3+CD4+
Standard Error 1.5

SECONDARY outcome

Timeframe: Before treatment to 1 month after therapy initiation

Population: The analysis population contains patients that had peripheral blood available for analysis from before and 1 month after initiating therapy along with being able to conduct the analysis on the marker. This resulted in the number of participants analyzed being less than the enrolled participants.

Flow cytometric analysis of T-cell surface markers before and 1 month after initiation therapy

Outcome measures

Outcome measures
Measure
MDX-010
n=13 Participants
Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) IV over 90 minutes on day 1. Treatment repeats every 28 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.
Mean Change in % of CD3+CD4- for the Marker CD45RO+
2.8 percentage of change of CD3+CD4-
Standard Error 0.9

Adverse Events

MDX-010

Serious events: 8 serious events
Other events: 16 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
MDX-010
n=18 participants at risk
Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) IV over 90 minutes on day 1. Treatment repeats every 28 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders
Anemia
5.6%
1/18 • Number of events 1
Gastrointestinal disorders
Diarrhea-No Colostom
16.7%
3/18 • Number of events 3
General disorders
Fatigue
5.6%
1/18 • Number of events 1
Investigations
Blood gonadotrophin abnormal
5.6%
1/18 • Number of events 1
Investigations
Lymphopenia
5.6%
1/18 • Number of events 1
Investigations
Platelet count decreased
5.6%
1/18 • Number of events 1
Investigations
Weight loss
11.1%
2/18 • Number of events 2
Metabolism and nutrition disorders
Anorexia
5.6%
1/18 • Number of events 1
Musculoskeletal and connective tissue disorders
Myalgia
5.6%
1/18 • Number of events 1
Nervous system disorders
Facial nerve disorder
5.6%
1/18 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Pneumonitis
5.6%
1/18 • Number of events 1

Other adverse events

Other adverse events
Measure
MDX-010
n=18 participants at risk
Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) IV over 90 minutes on day 1. Treatment repeats every 28 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders
Anemia
22.2%
4/18 • Number of events 7
Cardiac disorders
Atrial fibrillation
5.6%
1/18 • Number of events 1
Eye disorders
Dry eye
5.6%
1/18 • Number of events 3
Gastrointestinal disorders
Abdominal distension
5.6%
1/18 • Number of events 1
Gastrointestinal disorders
Constipation
11.1%
2/18 • Number of events 2
Gastrointestinal disorders
Diarrhea-No Colostom
50.0%
9/18 • Number of events 11
Gastrointestinal disorders
Dry mouth
5.6%
1/18 • Number of events 2
Gastrointestinal disorders
Lip pain
5.6%
1/18 • Number of events 2
Gastrointestinal disorders
Nausea
16.7%
3/18 • Number of events 4
Gastrointestinal disorders
Oral cavity Mucositis/stomatitis (functional/symptomatic)
5.6%
1/18 • Number of events 1
Gastrointestinal disorders
Pain-Abdominal
33.3%
6/18 • Number of events 9
Gastrointestinal disorders
Pain-Stomach
5.6%
1/18 • Number of events 1
Gastrointestinal disorders
Vomiting
11.1%
2/18 • Number of events 2
General disorders
Edema: Limb
11.1%
2/18 • Number of events 2
General disorders
Fatigue
66.7%
12/18 • Number of events 22
General disorders
Fever-No ANC
11.1%
2/18 • Number of events 2
General disorders
Rigors
5.6%
1/18 • Number of events 3
Investigations
Alkaline phosphatase
5.6%
1/18 • Number of events 1
Investigations
Aspartate aminotransferase increased
22.2%
4/18 • Number of events 5
Investigations
Creatinine
5.6%
1/18 • Number of events 1
Investigations
Leukopenia
22.2%
4/18 • Number of events 4
Investigations
Lymphopenia
5.6%
1/18 • Number of events 1
Investigations
Neutropenia
22.2%
4/18 • Number of events 5
Investigations
Platelet count decreased
27.8%
5/18 • Number of events 9
Investigations
Weight loss
5.6%
1/18 • Number of events 2
Metabolism and nutrition disorders
Anorexia
22.2%
4/18 • Number of events 6
Metabolism and nutrition disorders
Glucose intolerance
5.6%
1/18 • Number of events 2
Metabolism and nutrition disorders
Hyperglycemia
11.1%
2/18 • Number of events 5
Metabolism and nutrition disorders
Hyperkalemia
11.1%
2/18 • Number of events 4
Metabolism and nutrition disorders
Hypermatremia
5.6%
1/18 • Number of events 1
Metabolism and nutrition disorders
Hypocalcemia
5.6%
1/18 • Number of events 1
Musculoskeletal and connective tissue disorders
Arthralgia
5.6%
1/18 • Number of events 2
Musculoskeletal and connective tissue disorders
Chest wall pain
5.6%
1/18 • Number of events 3
Musculoskeletal and connective tissue disorders
Myalgia
16.7%
3/18 • Number of events 3
Musculoskeletal and connective tissue disorders
Neck pain
5.6%
1/18 • Number of events 2
Musculoskeletal and connective tissue disorders
Pain in extremity
5.6%
1/18 • Number of events 1
Nervous system disorders
Headache
22.2%
4/18 • Number of events 6
Reproductive system and breast disorders
Impotence
5.6%
1/18 • Number of events 3
Reproductive system and breast disorders
Pelvic pain
5.6%
1/18 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Cough
5.6%
1/18 • Number of events 2
Respiratory, thoracic and mediastinal disorders
Dyspnea
11.1%
2/18 • Number of events 5
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
5.6%
1/18 • Number of events 2
Respiratory, thoracic and mediastinal disorders
Pleural effusion
5.6%
1/18 • Number of events 2
Respiratory, thoracic and mediastinal disorders
Pulmonary
5.6%
1/18 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Rhinitis Allergic
5.6%
1/18 • Number of events 1
Skin and subcutaneous tissue disorders
Pain of skin
5.6%
1/18 • Number of events 1
Skin and subcutaneous tissue disorders
Pruritus
11.1%
2/18 • Number of events 5
Skin and subcutaneous tissue disorders
Rash/Desquamation
16.7%
3/18 • Number of events 6
Skin and subcutaneous tissue disorders
Sweating
5.6%
1/18 • Number of events 1
Vascular disorders
Hot flashes
5.6%
1/18 • Number of events 1

Additional Information

Dr. Stephen Ansell

Mayo Clinic

Phone: 507-284-0923

Results disclosure agreements

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

Restriction type: LTE60