Trial Outcomes & Findings for High Dose Rituximab for Initial Treatment of Indolent B-Cell Lymphomas (NCT NCT00895661)
NCT ID: NCT00895661
Last Updated: 2017-06-09
Results Overview
CR requires all of the following: 1. Regression to normal size on CT (≤ 1.5 cm in their greatest transverse diameter for nodes ≥ 1.5 cm before therapy). Previously involved nodes that were 1.1 to 1.5 cm in their greatest transverse diameter before treatment must have decreased to \<1 cm in their greatest transverse diameter after treatment, or by more than 75% in the sum of the products of the greatest diameters (SPD). 2. The spleen, if considered to be enlarged before therapy on the basis of a CT scan, must have regressed in size and must not be palpable on physical examination. 3. If bone marrow is known to be involved at the beginning, then repeat biopsy documents clearance
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
40 participants
Primary outcome timeframe
after a median number of 8 maintenance cycles, up to 24 weeks
Results posted on
2017-06-09
Participant Flow
Participant milestones
| Measure |
Rituximab
single-arm, open-label, interventional
rituximab: Increased dose (750 mg/m2) intravenously for 4 weekly doses followed by maintenance dosing once every three months for up to 2 years. Maintenance dose is standard (375 mg/m2).
|
|---|---|
|
Overall Study
STARTED
|
40
|
|
Overall Study
COMPLETED
|
37
|
|
Overall Study
NOT COMPLETED
|
3
|
Reasons for withdrawal
| Measure |
Rituximab
single-arm, open-label, interventional
rituximab: Increased dose (750 mg/m2) intravenously for 4 weekly doses followed by maintenance dosing once every three months for up to 2 years. Maintenance dose is standard (375 mg/m2).
|
|---|---|
|
Overall Study
Death
|
1
|
|
Overall Study
reason unknown
|
2
|
Baseline Characteristics
High Dose Rituximab for Initial Treatment of Indolent B-Cell Lymphomas
Baseline characteristics by cohort
| Measure |
Rituximab
n=40 Participants
single-arm, open-label, interventional
rituximab: Increased dose (750 mg/m2) intravenously for 4 weekly doses followed by maintenance dosing once every three months for up to 2 years. Maintenance dose is standard (375 mg/m2).
|
|---|---|
|
Age, Continuous
|
60 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
27 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
40 participants
n=5 Participants
|
|
Lymphoma type
Follicular
|
31 Participants
n=5 Participants
|
|
Lymphoma type
Marginal zone
|
4 Participants
n=5 Participants
|
|
Lymphoma type
Small lymphocytic
|
3 Participants
n=5 Participants
|
|
Lymphoma type
Indolent B cell, not otherwise specified
|
2 Participants
n=5 Participants
|
|
Involvement of >4 nodal sites
|
17 Participants
n=5 Participants
|
|
Hgb<12 g/dL
|
9 Participants
n=5 Participants
|
|
elevated LDH (Lactate dehydrogenase)
|
11 Participants
n=5 Participants
|
|
Follicular lymphoma prognostic index (FLIPI)
Low risk
|
6 Participants
n=5 Participants
|
|
Follicular lymphoma prognostic index (FLIPI)
Intermediate risk
|
15 Participants
n=5 Participants
|
|
Follicular lymphoma prognostic index (FLIPI)
High risk
|
17 Participants
n=5 Participants
|
|
Follicular lymphoma prognostic index (FLIPI)
FLIPI score not available
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: after a median number of 8 maintenance cycles, up to 24 weeksCR requires all of the following: 1. Regression to normal size on CT (≤ 1.5 cm in their greatest transverse diameter for nodes ≥ 1.5 cm before therapy). Previously involved nodes that were 1.1 to 1.5 cm in their greatest transverse diameter before treatment must have decreased to \<1 cm in their greatest transverse diameter after treatment, or by more than 75% in the sum of the products of the greatest diameters (SPD). 2. The spleen, if considered to be enlarged before therapy on the basis of a CT scan, must have regressed in size and must not be palpable on physical examination. 3. If bone marrow is known to be involved at the beginning, then repeat biopsy documents clearance
Outcome measures
| Measure |
Rituximab
n=40 Participants
single-arm, open-label, interventional
rituximab: Increased dose (750 mg/m2) intravenously for 4 weekly doses followed by maintenance dosing once every three months for up to 2 years. Maintenance dose is standard (375 mg/m2).
|
|---|---|
|
Determine Complete Response Rate (CRR) of Increased Dose Rituximab in Indolent B-cell Lymphomas
|
21 Participants
|
SECONDARY outcome
Timeframe: after a median number of 8 maintenance cycles, up to 24 weeksComplete Response (CR): see definition in primary outcome Partial Response (PR): 1. ≥50% decrease in SPD of up to 6 largest dominant masses 2. No new sites of disease or increase in the size of the other nodes, liver, or spleen. 3. Splenic and hepatic nodules must regress by at least 50% in the SPD. Overall Response (OR) = CR + PR.
Outcome measures
| Measure |
Rituximab
n=40 Participants
single-arm, open-label, interventional
rituximab: Increased dose (750 mg/m2) intravenously for 4 weekly doses followed by maintenance dosing once every three months for up to 2 years. Maintenance dose is standard (375 mg/m2).
|
|---|---|
|
Overall Response Rate (ORR)
|
32 Participants
|
SECONDARY outcome
Timeframe: 5 yearsProgressive Disease (PD) or Relapsed Disease (RD): 1. Appearance of a new lesion(s) \> 1.5 cm in any axis, ≥ 50% increase in SPD of more than one node, or ≥50% increase in longest diameter of a previously identified node \> 1 cm in short axis. 2. \>50% increase from nadir in the SPD of any previous lesions PFS is number of participants who have not died or had PD or RD.
Outcome measures
| Measure |
Rituximab
n=40 Participants
single-arm, open-label, interventional
rituximab: Increased dose (750 mg/m2) intravenously for 4 weekly doses followed by maintenance dosing once every three months for up to 2 years. Maintenance dose is standard (375 mg/m2).
|
|---|---|
|
Progression-free Survival (PFS)
|
19 Participants
|
SECONDARY outcome
Timeframe: 24 monthsToxicity grades: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening
Outcome measures
| Measure |
Rituximab
n=40 Participants
single-arm, open-label, interventional
rituximab: Increased dose (750 mg/m2) intravenously for 4 weekly doses followed by maintenance dosing once every three months for up to 2 years. Maintenance dose is standard (375 mg/m2).
|
|---|---|
|
Incidence of Severity of Infusion Reactions, Infections and Neutropenia
Grade 3/4 neutropenia
|
3 Participants
|
|
Incidence of Severity of Infusion Reactions, Infections and Neutropenia
Any allergic reactions with infusions
|
19 Participants
|
|
Incidence of Severity of Infusion Reactions, Infections and Neutropenia
Grade 3 allergic reactions with infusions
|
2 Participants
|
Adverse Events
Rituximab
Serious events: 4 serious events
Other events: 40 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Rituximab
n=40 participants at risk
single-arm, open-label, interventional
rituximab: Increased dose (750 mg/m2) intravenously for 4 weekly doses followed by maintenance dosing once every three months for up to 2 years. Maintenance dose is standard (375 mg/m2).
|
|---|---|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
2.5%
1/40 • Number of events 1
|
|
Gastrointestinal disorders
Small bowel obstruction
|
2.5%
1/40 • Number of events 1
|
|
Infections and infestations
Cellulitis (toe)
|
2.5%
1/40 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
2.5%
1/40 • Number of events 1
|
Other adverse events
| Measure |
Rituximab
n=40 participants at risk
single-arm, open-label, interventional
rituximab: Increased dose (750 mg/m2) intravenously for 4 weekly doses followed by maintenance dosing once every three months for up to 2 years. Maintenance dose is standard (375 mg/m2).
|
|---|---|
|
Blood and lymphatic system disorders
Neutrophils
|
100.0%
40/40 • Number of events 495
|
|
Immune system disorders
Allergic reaction
|
100.0%
40/40 • Number of events 493
|
|
Infections and infestations
Infection-other
|
100.0%
40/40 • Number of events 493
|
|
Metabolism and nutrition disorders
Tumor lysis syndrome
|
100.0%
40/40 • Number of events 493
|
|
General disorders
Fatigue
|
60.0%
24/40 • Number of events 97
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
37.5%
15/40 • Number of events 34
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
35.0%
14/40 • Number of events 52
|
|
Blood and lymphatic system disorders
Hemoglobin
|
32.5%
13/40 • Number of events 38
|
|
Gastrointestinal disorders
Diarrhea w/o prior colostomy
|
27.5%
11/40 • Number of events 32
|
|
Blood and lymphatic system disorders
Leukocytes
|
27.5%
11/40 • Number of events 32
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
25.0%
10/40 • Number of events 19
|
|
Infections and infestations
Infection Gr0-2 neut- upper airway
|
25.0%
10/40 • Number of events 14
|
|
General disorders
Fever w/o neutropenia
|
25.0%
10/40 • Number of events 12
|
|
General disorders
Abdomen- pain
|
22.5%
9/40 • Number of events 21
|
|
Gastrointestinal disorders
Nausea
|
22.5%
9/40 • Number of events 21
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
22.5%
9/40 • Number of events 19
|
|
Nervous system disorders
Dizziness
|
20.0%
8/40 • Number of events 21
|
|
Immune system disorders
Allergic rhinitis
|
20.0%
8/40 • Number of events 20
|
|
General disorders
Head/headache
|
20.0%
8/40 • Number of events 20
|
|
General disorders
Sweating
|
20.0%
8/40 • Number of events 19
|
|
Skin and subcutaneous tissue disorders
Skin-other
|
20.0%
8/40 • Number of events 16
|
|
General disorders
Back-pain
|
20.0%
8/40 • Number of events 10
|
|
Blood and lymphatic system disorders
Lymphopenia
|
17.5%
7/40 • Number of events 15
|
|
General disorders
Pain-other
|
17.5%
7/40 • Number of events 11
|
|
General disorders
Insomnia
|
15.0%
6/40 • Number of events 27
|
|
General disorders
Pelvic-pain
|
15.0%
6/40 • Number of events 15
|
|
General disorders
Joint-pain
|
15.0%
6/40 • Number of events 14
|
|
Nervous system disorders
Anxiety
|
12.5%
5/40 • Number of events 18
|
|
Gastrointestinal disorders
Anorexia
|
12.5%
5/40 • Number of events 13
|
|
Metabolism and nutrition disorders
AST- SGOT
|
12.5%
5/40 • Number of events 8
|
|
Gastrointestinal disorders
Dyspepsia
|
12.5%
5/40 • Number of events 7
|
|
Blood and lymphatic system disorders
Platelets
|
12.5%
5/40 • Number of events 6
|
|
Infections and infestations
Infection Gr0-2 neut- bronchus
|
12.5%
5/40 • Number of events 5
|
|
General disorders
Rigors/chills
|
12.5%
5/40 • Number of events 5
|
|
Nervous system disorders
Neuropathy-sensory
|
10.0%
4/40 • Number of events 18
|
|
Metabolism and nutrition disorders
Alkaline phosphatase
|
10.0%
4/40 • Number of events 13
|
|
Metabolism and nutrition disorders
ALT- SGPT
|
10.0%
4/40 • Number of events 10
|
|
General disorders
Extremity-limb- pain
|
10.0%
4/40 • Number of events 10
|
|
Skin and subcutaneous tissue disorders
Rash: acne/acneiform
|
10.0%
4/40 • Number of events 9
|
|
Infections and infestations
Infection Gr0-2 neut- sinus
|
10.0%
4/40 • Number of events 6
|
|
General disorders
Neck- pain
|
10.0%
4/40 • Number of events 6
|
|
Gastrointestinal disorders
Vomiting
|
10.0%
4/40 • Number of events 6
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
7.5%
3/40 • Number of events 9
|
|
Renal and urinary disorders
Urinary frequency/urgency
|
7.5%
3/40 • Number of events 8
|
|
Gastrointestinal disorders
Constipation
|
7.5%
3/40 • Number of events 7
|
|
Metabolism and nutrition disorders
Creatinine
|
7.5%
3/40 • Number of events 6
|
|
Gastrointestinal disorders
GI-other
|
7.5%
3/40 • Number of events 6
|
|
Ear and labyrinth disorders
Hearing-other
|
7.5%
3/40 • Number of events 6
|
|
Blood and lymphatic system disorders
Edema head and neck
|
7.5%
3/40 • Number of events 5
|
|
Blood and lymphatic system disorders
Hematologic-other
|
7.5%
3/40 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary/Upper Respiratory-other
|
7.5%
3/40 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm- wheezing
|
7.5%
3/40 • Number of events 4
|
|
General disorders
Chest/thoracic pain NOS
|
7.5%
3/40 • Number of events 4
|
|
General disorders
Muscle- pain
|
7.5%
3/40 • Number of events 4
|
|
General disorders
Flu-like syndrome
|
7.5%
3/40 • Number of events 3
|
|
Metabolism and nutrition disorders
Hypokalemia
|
7.5%
3/40 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal/soft tissue-other
|
7.5%
3/40 • Number of events 3
|
|
Cardiac disorders
Palpitations
|
7.5%
3/40 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
5.0%
2/40 • Number of events 9
|
|
Cardiac disorders
Sinus bradycardia
|
5.0%
2/40 • Number of events 9
|
|
Gastrointestinal disorders
Dysphagia
|
5.0%
2/40 • Number of events 8
|
|
Cardiac disorders
Sinus tachycardia
|
5.0%
2/40 • Number of events 7
|
|
Hepatobiliary disorders
Cholecystitis
|
5.0%
2/40 • Number of events 6
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
5.0%
2/40 • Number of events 5
|
|
Gastrointestinal disorders
Muco/stomatitis (symptom) oral cavity
|
5.0%
2/40 • Number of events 5
|
|
Gastrointestinal disorders
Dry mouth
|
5.0%
2/40 • Number of events 3
|
|
Gastrointestinal disorders
Esophagitis
|
5.0%
2/40 • Number of events 3
|
|
Endocrine disorders
Hyopthyroidism
|
5.0%
2/40 • Number of events 3
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
5.0%
2/40 • Number of events 3
|
|
Infections and infestations
Infection Gr0-2 neut- skin
|
5.0%
2/40 • Number of events 3
|
|
Infections and infestations
Infection Gr0-2 neut- urinary tract
|
5.0%
2/40 • Number of events 3
|
|
Ear and labyrinth disorders
Otitis- middle ear (non-infectious)
|
5.0%
2/40 • Number of events 3
|
|
Gastrointestinal disorders
Taste disturbance
|
5.0%
2/40 • Number of events 3
|
|
General disorders
Chest wall- pain
|
5.0%
2/40 • Number of events 2
|
|
Gastrointestinal disorders
Dehydration
|
5.0%
2/40 • Number of events 2
|
|
Blood and lymphatic system disorders
Edema limb
|
5.0%
2/40 • Number of events 2
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
5.0%
2/40 • Number of events 2
|
|
Metabolism and nutrition disorders
Hyponatremia
|
5.0%
2/40 • Number of events 2
|
|
Infections and infestations
Infection Gr0-2 neut- lung
|
5.0%
2/40 • Number of events 2
|
|
Metabolism and nutrition disorders
Metabolic/Laboratory-other
|
5.0%
2/40 • Number of events 2
|
|
Eye disorders
Ocular-other
|
5.0%
2/40 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Voice changes/dysarthria
|
5.0%
2/40 • Number of events 2
|
|
General disorders
Weight gain
|
5.0%
2/40 • Number of events 2
|
|
General disorders
Weight loss
|
5.0%
2/40 • Number of events 2
|
Additional Information
Jeremy Abramson, MD
Massachusetts General Hospital Cancer Center
Phone: 617-724-4000
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place