Trial Outcomes & Findings for Investigating the Safety and Efficacy of Rituximab and Pembrolizumab in Relapsed/Refractory Waldenström's Macroglobulinaemia (NCT NCT03630042)
NCT ID: NCT03630042
Last Updated: 2024-11-07
Results Overview
The primary outcome is the percentage of patients achieving at least a major response rate at 24 weeks post commencing treatment. A major response rate is defined as a greater than 50% reduction in paraprotein measurement - this is in line with international recognised response criteria for the disease under investigation. In this single arm study all patients receiving treatment were considered applicable for endpoint analysis. There is no comparison as there is only one arm.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
17 participants
Primary outcome timeframe
24 weeks
Results posted on
2024-11-07
Participant Flow
Participant milestones
| Measure |
Pembrolizumab and Rituximab
Pembrolizumab: 200 mg IV dose given on day 1 of a three week cycle
Rituximab: 375 mg/m2 IV dose given up to 8 times in the trial
|
|---|---|
|
Overall Study
STARTED
|
17
|
|
Overall Study
COMPLETED
|
17
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Pembrolizumab and Rituximab
n=17 Participants
Pembrolizumab: 200 mg IV dose given on day 1 of a three week cycle
Rituximab: 375 mg/m2 IV dose given up to 8 times in the trial
|
|---|---|
|
Age, Continuous
|
70.4 years
n=17 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=17 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=17 Participants
|
|
ECOG Performance Status
ECOG 0
|
9 Participants
n=17 Participants
|
|
ECOG Performance Status
ECOG 1
|
7 Participants
n=17 Participants
|
|
ECOG Performance Status
ECOG 2
|
1 Participants
n=17 Participants
|
PRIMARY outcome
Timeframe: 24 weeksThe primary outcome is the percentage of patients achieving at least a major response rate at 24 weeks post commencing treatment. A major response rate is defined as a greater than 50% reduction in paraprotein measurement - this is in line with international recognised response criteria for the disease under investigation. In this single arm study all patients receiving treatment were considered applicable for endpoint analysis. There is no comparison as there is only one arm.
Outcome measures
| Measure |
Pembrolizumab and Rituximab
n=17 Participants
Pembrolizumab: 200 mg IV dose given on day 1 of a three week cycle
Rituximab: 375 mg/m2 IV dose given up to 8 times in the trial
|
|---|---|
|
Percentage of Patients Achieving at Least a Major Response Rate at 24 Weeks Post Commencing Treatment
|
8 Participants
|
SECONDARY outcome
Timeframe: until 5 months post last IMP administrationAs assessed by the number and grade of serious and non-serious adverse events, graded according to CTCAE v5.0
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 weeksOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 weeksOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Assessed at 12 weeks, 24 weeks and 1 year after commencing treatmentOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Assessed once per year after completing treatment (average of 1 year)as determined by the time from registration to the next line of therapy
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 1 and 2 years post commencing treatmentOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 1 and 2 years post commencing treatmentOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 weeksChange in quality of life (QoL) at 24 weeks post commencing treatment as assessed by EORTC QLQ-C30 questionnaire. Daily activities and thoughts/feelings experienced by the patient over the week preceding questionnaire completion are graded on a scale from '1-not at all' to '4-very much'. Also rating of overall health and quality of life from '1-very poor' to '7-excellent'
Outcome measures
Outcome data not reported
Adverse Events
Pembrolizumab and Rituximab
Serious events: 10 serious events
Other events: 17 other events
Deaths: 5 deaths
Serious adverse events
| Measure |
Pembrolizumab and Rituximab
n=17 participants at risk
Pembrolizumab: 200 mg IV dose given on day 1 of a three week cycle
Rituximab: 375 mg/m2 IV dose given up to 8 times in the trial
|
|---|---|
|
General disorders
Fatigue
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
General disorders
Fever
|
17.6%
3/17 • Between informed consent and 5 months post last IMP administration.
|
|
Infections and infestations
Covid-19
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Infections and infestations
Infection (unknown origin)
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Reproductive system and breast disorders
Lung infection
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Injury, poisoning and procedural complications
Vaccination complication
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Investigations
Creatinine increased
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Investigations
Neutrophil count decreased
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Nervous system disorders
Stroke
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Nervous system disorders
Syncope
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
Other adverse events
| Measure |
Pembrolizumab and Rituximab
n=17 participants at risk
Pembrolizumab: 200 mg IV dose given on day 1 of a three week cycle
Rituximab: 375 mg/m2 IV dose given up to 8 times in the trial
|
|---|---|
|
Investigations
Platelet count decreased
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Investigations
Weight loss
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Investigations
Creatinine increased
|
29.4%
5/17 • Between informed consent and 5 months post last IMP administration.
|
|
Investigations
White blood cell decreased
|
23.5%
4/17 • Between informed consent and 5 months post last IMP administration.
|
|
Investigations
Blood bicarbonate decreased
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Investigations
Aspartate aminotransferase increased
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Investigations
Alanine aminotransferase increased
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Investigations
Lymphocyte count decreased
|
23.5%
4/17 • Between informed consent and 5 months post last IMP administration.
|
|
Investigations
Serum amylase increased
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Investigations
Neutrophil count decreased
|
23.5%
4/17 • Between informed consent and 5 months post last IMP administration.
|
|
Investigations
Thyroid stimulating hormone increased
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Investigations
White blood cell increased
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Investigations
Platelet count increased
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Investigations
Increased neutrophils
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
17.6%
3/17 • Between informed consent and 5 months post last IMP administration.
|
|
Metabolism and nutrition disorders
Iron deficiency
|
17.6%
3/17 • Between informed consent and 5 months post last IMP administration.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Musculoskeletal and connective tissue disorders
Muscle cramp
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Musculoskeletal and connective tissue disorders
Polymylagia rheumatica
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Excision of basal cell carcinoma
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma trunk
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Nervous system disorders
Dizziness
|
23.5%
4/17 • Between informed consent and 5 months post last IMP administration.
|
|
Nervous system disorders
Headache
|
17.6%
3/17 • Between informed consent and 5 months post last IMP administration.
|
|
Nervous system disorders
Paresthesia
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Nervous system disorders
Stroke
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Nervous system disorders
Memory impairment
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Nervous system disorders
Syncope
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Nervous system disorders
Peripheral neuropathy
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Nervous system disorders
Sciatica pain (right leg)
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Renal and urinary disorders
Urinary frequency
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Renal and urinary disorders
Dysuria
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Renal and urinary disorders
Chronic kidney disease
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
17.6%
3/17 • Between informed consent and 5 months post last IMP administration.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Respiratory, thoracic and mediastinal disorders
Stridor
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Respiratory, thoracic and mediastinal disorders
Other/hemoptysis
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
17.6%
3/17 • Between informed consent and 5 months post last IMP administration.
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
17.6%
3/17 • Between informed consent and 5 months post last IMP administration.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Vascular disorders
Hypotension
|
23.5%
4/17 • Between informed consent and 5 months post last IMP administration.
|
|
Vascular disorders
Flushing
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Skin and subcutaneous tissue disorders
Skin lesion (forehead)
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Blood and lymphatic system disorders
Neutropenia
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Blood and lymphatic system disorders
Anemia
|
47.1%
8/17 • Between informed consent and 5 months post last IMP administration.
|
|
Blood and lymphatic system disorders
Folate deficiency
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Cardiac disorders
Atrial fibrillation
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Cardiac disorders
Sinus tachycardia
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Cardiac disorders
Atrioventricular block first degree
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Cardiac disorders
Palpitations
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Cardiac disorders
Ventricular arrhythmia
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Cardiac disorders
Heart failure with preserved ejection fraction
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Ear and labyrinth disorders
Tinnitus
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Endocrine disorders
Adrenal insufficiency
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Eye disorders
Blurred vision
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Gastrointestinal disorders
Dry mouth
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Gastrointestinal disorders
Hemorrhoids
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Gastrointestinal disorders
Constipation
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Gastrointestinal disorders
Diarrhea
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Gastrointestinal disorders
Nausea
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Gastrointestinal disorders
Abdominal pain
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Gastrointestinal disorders
Dyspepsia
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Gastrointestinal disorders
Loose stools
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Gastrointestinal disorders
Mouth ulcer
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
General disorders
Chills
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
General disorders
Localized edema
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
General disorders
Fever
|
35.3%
6/17 • Between informed consent and 5 months post last IMP administration.
|
|
General disorders
Facial pain
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
General disorders
Fatigue
|
29.4%
5/17 • Between informed consent and 5 months post last IMP administration.
|
|
General disorders
Shoulder pain
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
General disorders
Intermittent pain in fingers
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Infections and infestations
Lymph gland infection
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Infections and infestations
Lung infection
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Infections and infestations
Thrush
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Infections and infestations
Infection
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Infections and infestations
covid-19
|
11.8%
2/17 • Between informed consent and 5 months post last IMP administration.
|
|
Infections and infestations
chest infection
|
5.9%
1/17 • Between informed consent and 5 months post last IMP administration.
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
41.2%
7/17 • Between informed consent and 5 months post last IMP administration.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place