Trial Outcomes & Findings for Rituximab Plus Lenalidomide in Patients With Mucosa Associated Lymphoid Tissue (NCT NCT01611259)

Last Updated: 2017-11-06

Results Overview

The primary objective of this Phase II study is to evaluate the proportion of patients responding to Lenalidomide and Rituximab. In case of a response rate of \< 40%, the combination is rejected as ineffective, while an active combination is defined at a minimum response rate of 60% based of findings with rituximab and lenalidomide mono-therapy.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

50 participants

Primary outcome timeframe

40 weeks

Results posted on

2017-11-06

Participant Flow

50 patients were enrolled at 4 sites in Austria. First patient in was 06-Jun-2012; Last patient in was 26-May-2014.

2 patients were withdrawn before first response evaluation and were replaced. 2 patients withdrew their consents prior to study treatment and did not experience AEs to other study procedures. These 2 patients were therefore excluded from intent-to-treat (ITT) efficacy assessments, safety assessments and listing of baseline characteristics.

Participant milestones

Participant milestones
Measure	Rituximab and Lenalidomide Rituximab was administered on day 1 of each cycle in a dose of 375 mg/m² (28 day cycle). Dose of lenalidomide for investigation is 20 mg/day, orally on days 1 to 21 followed by 7 days pause.Restaging should be performed after three cycles. In case of at least stable disease, patients should receive another three courses of therapy. Patients with documented CR after 6 courses stopped therapy/study, while patients with PR or SD were given another two cycles for a maximum of 8 cycles.
Overall Study STARTED	48
Overall Study COMPLETED	34
Overall Study NOT COMPLETED	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Rituximab and Lenalidomide Rituximab was administered on day 1 of each cycle in a dose of 375 mg/m² (28 day cycle). Dose of lenalidomide for investigation is 20 mg/day, orally on days 1 to 21 followed by 7 days pause.Restaging should be performed after three cycles. In case of at least stable disease, patients should receive another three courses of therapy. Patients with documented CR after 6 courses stopped therapy/study, while patients with PR or SD were given another two cycles for a maximum of 8 cycles.
Overall Study Physician Decision	1
Overall Study Lack of Efficacy	2
Overall Study Adverse Event	4
Overall Study Withdrawal by Subject	7

Baseline Characteristics

Rituximab Plus Lenalidomide in Patients With Mucosa Associated Lymphoid Tissue

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rituximab and Lenalidomide n=48 Participants Rituximab was administered on day 1 of each cycle in a dose of 375 mg/m² (28 day cycle). Dose of lenalidomide for investigation is 20 mg/day, orally on days 1 to 21 followed by 7 days pause.Restaging should be performed after three cycles. In case of at least stable disease, patients should receive another three courses of therapy. Patients with documented CR after 6 courses stopped therapy/study, while patients with PR or SD were given another two cycles for a maximum of 8 cycles.
Age, Continuous	65 years n=5 Participants
Sex: Female, Male Female	29 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants

PRIMARY outcome

Timeframe: 40 weeks

Population: 48 patients were included into safety assessment, two of them received treatment but no efficacy assessment was available. Therefore, these two patients were neither included into Intention-to-treat nor Per-protocol efficacy analysis.

Outcome measures

Outcome measures
Measure	Rituximab and Lenalidomide n=46 Participants Rituximab was administered on day 1 of each cycle in a dose of 375 mg/m² (28 day cycle). Dose of lenalidomide for investigation is 20 mg/day, orally on days 1 to 21 followed by 7 days pause.Restaging should be performed after three cycles. In case of at least stable disease, patients should receive another three courses of therapy. Patients with documented CR after 6 courses stopped therapy/study, while patients with PR or SD were given another two cycles for a maximum of 8 cycles.
Objective Responses in Patients With MALT Lymphoma Presenting With Measureable Disease CR	25 Participants
Objective Responses in Patients With MALT Lymphoma Presenting With Measureable Disease PR or SD	20 Participants
Objective Responses in Patients With MALT Lymphoma Presenting With Measureable Disease PD	1 Participants

SECONDARY outcome

Timeframe: From treatment start until 28 days after last study treatment; expected study duration 24 months

Safety of Rituximab (Mabthera®) plus Lenalidomide (Revlimid®) in this patient population

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1, 14 and 28 of cycle 1 and day 1 of cycle 5

T-cell subsets will be evaluated from EDTA blood in a central lab

Outcome measures

Outcome data not reported

Adverse Events

Rituximab and Lenalidomide

Serious events: 18 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Rituximab and Lenalidomide n=48 participants at risk Rituximab was administered on day 1 of each cycle in a dose of 375 mg/m² (28 day cycle). Dose of lenalidomide for investigation is 20 mg/day, orally on days 1 to 21 followed by 7 days pause.Restaging should be performed after three cycles. In case of at least stable disease, patients should receive another three courses of therapy. Patients with documented CR after 6 courses stopped therapy/study, while patients with PR or SD were given another two cycles for a maximum of 8 cycles.
Injury, poisoning and procedural complications Infusion related reaction	2.1% 1/48 • Number of events 1 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	2.1% 1/48 • Number of events 1 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Blood and lymphatic system disorders Anemia	2.1% 1/48 • Number of events 1 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
General disorders Pain	2.1% 1/48 • Number of events 1 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
General disorders Pyrexia	4.2% 2/48 • Number of events 2 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Gastrointestinal disorders Diarrhea	2.1% 1/48 • Number of events 1 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Gastrointestinal disorders Gastric haemorrhage	2.1% 1/48 • Number of events 1 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Gastrointestinal disorders Vomiting	2.1% 1/48 • Number of events 1 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Renal and urinary disorders Renal failure	2.1% 1/48 • Number of events 1 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Renal and urinary disorders Urinary retention	2.1% 1/48 • Number of events 1 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Hepatobiliary disorders Colecystitis	2.1% 1/48 • Number of events 1 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Skin and subcutaneous tissue disorders Rash	4.2% 2/48 • Number of events 2 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Musculoskeletal and connective tissue disorders Back pain	2.1% 1/48 • Number of events 1 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Infections and infestations Bacterial infection	2.1% 1/48 • Number of events 1 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Infections and infestations Bronchitis	2.1% 1/48 • Number of events 1 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Infections and infestations Infection	2.1% 1/48 • Number of events 1 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Infections and infestations Lung infection	2.1% 1/48 • Number of events 1 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Infections and infestations Skin infection	2.1% 1/48 • Number of events 1 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.

Other adverse events

Other adverse events
Measure	Rituximab and Lenalidomide n=48 participants at risk Rituximab was administered on day 1 of each cycle in a dose of 375 mg/m² (28 day cycle). Dose of lenalidomide for investigation is 20 mg/day, orally on days 1 to 21 followed by 7 days pause.Restaging should be performed after three cycles. In case of at least stable disease, patients should receive another three courses of therapy. Patients with documented CR after 6 courses stopped therapy/study, while patients with PR or SD were given another two cycles for a maximum of 8 cycles.
Blood and lymphatic system disorders Leucocyte count	12.5% 6/48 • Number of events 15 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Eye disorders Conjunctivitis	4.2% 2/48 • Number of events 3 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Gastrointestinal disorders Abdominal pain upper	4.2% 2/48 • Number of events 2 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Gastrointestinal disorders Constipation	20.8% 10/48 • Number of events 11 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Gastrointestinal disorders Diarrhoea	18.8% 9/48 • Number of events 16 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Gastrointestinal disorders Dry mouth	8.3% 4/48 • Number of events 5 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Gastrointestinal disorders Dysgeusia	6.2% 3/48 • Number of events 3 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Gastrointestinal disorders Dyspepsia	6.2% 3/48 • Number of events 4 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Gastrointestinal disorders Gastroenteritis	4.2% 2/48 • Number of events 2 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Gastrointestinal disorders Gastrointestinal pain	6.2% 3/48 • Number of events 3 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Gastrointestinal disorders Meteorism	4.2% 2/48 • Number of events 2 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Gastrointestinal disorders Nausea	14.6% 7/48 • Number of events 10 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Gastrointestinal disorders Stomatitis	4.2% 2/48 • Number of events 3 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Gastrointestinal disorders Vomiting	10.4% 5/48 • Number of events 5 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
General disorders Chills	18.8% 9/48 • Number of events 10 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
General disorders Condition aggravated	4.2% 2/48 • Number of events 2 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
General disorders Fatigue	35.4% 17/48 • Number of events 20 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
General disorders Infusion related reaction	4.2% 2/48 • Number of events 4 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
General disorders Mucositis	4.2% 2/48 • Number of events 3 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
General disorders Night sweats	6.2% 3/48 • Number of events 4 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
General disorders Oedema peripheral	10.4% 5/48 • Number of events 6 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
General disorders Pyrexia	16.7% 8/48 • Number of events 9 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Immune system disorders Hypersensitivity	10.4% 5/48 • Number of events 6 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Infections and infestations Bronchitis	4.2% 2/48 • Number of events 2 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Infections and infestations Infection	4.2% 2/48 • Number of events 2 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Infections and infestations Nasopharyngitis	4.2% 2/48 • Number of events 2 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Infections and infestations Oral herpes	8.3% 4/48 • Number of events 4 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Injury, poisoning and procedural complications Overdose	6.2% 3/48 • Number of events 3 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Investigations Alanine aminotransferase increased	4.2% 2/48 • Number of events 2 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Investigations Haemoglobin	6.2% 3/48 • Number of events 5 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Investigations Lymphocyte count	6.2% 3/48 • Number of events 6 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Investigations Neutrophil count	25.0% 12/48 • Number of events 28 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Investigations Platelet count	6.2% 3/48 • Number of events 7 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Musculoskeletal and connective tissue disorders Arthralgia	8.3% 4/48 • Number of events 5 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Musculoskeletal and connective tissue disorders Muscle spasms	12.5% 6/48 • Number of events 8 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	22.9% 11/48 • Number of events 15 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Nervous system disorders Headache	12.5% 6/48 • Number of events 11 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Nervous system disorders Insomnia	10.4% 5/48 • Number of events 6 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Nervous system disorders Tremor	4.2% 2/48 • Number of events 3 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Nervous system disorders Vertigo	22.9% 11/48 • Number of events 12 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Renal and urinary disorders Nocturia	4.2% 2/48 • Number of events 2 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Renal and urinary disorders Urinary tract infection	12.5% 6/48 • Number of events 6 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	22.9% 11/48 • Number of events 11 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.2% 3/48 • Number of events 3 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Skin and subcutaneous tissue disorders Eyelid oedema	4.2% 2/48 • Number of events 5 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Skin and subcutaneous tissue disorders Pruritus	47.9% 23/48 • Number of events 34 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Skin and subcutaneous tissue disorders Rash	47.9% 23/48 • Number of events 39 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Skin and subcutaneous tissue disorders Skin ulcer	4.2% 2/48 • Number of events 2 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.
Vascular disorders Thrombosis	4.2% 2/48 • Number of events 2 • All AEs were recorded by the Investigator from the time the subject signs informed consent to 28 days after the last dose of study medication.

Additional Information

Public contact Daniela Wolkersdorfer

AGMT

Phone: 00436626404411

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER