NCT01125176: ThRiL

Alternating Thalidomide and Lenalidomide Therapy Plus Rituximab (ThRiL) as Initial Treatment for Patients With CLL

Completed Phase 2 Results posted Last updated 21 January 2022

What this trial tests

Phase 2 trial testing thalidomide in Chronic Lymphocytic Leukemia in 15 participants. Completed in 29 December 2020.

Timeline

30 March 2012

Primary endpoint
20 December 2018

29 December 2020

Quick facts

Lead sponsor	Weill Medical College of Cornell University
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	15
Start date	30 March 2012
Primary completion	20 December 2018
Estimated completion	29 December 2020
Sites	1 location across United States

Drugs / interventions tested

• thalidomide (THALIDOMIDE) — full drug profile →
• lenalidomide — full drug profile →
• rituximab — full drug profile →

Conditions studied

• Chronic Lymphocytic Leukemia — all drugs for Chronic Lymphocytic Leukemia →

Sponsor

Weill Medical College of Cornell University

Who can join

18 and older, any sex, with Chronic Lymphocytic Leukemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Response Rate as Defined as the Number of Patients Who Experience a Response (Complete or Partial) to Treatment at the Time of Best Response Primary · From date of study drug initiation until date of best response, assessed up to 6 years.

Response will be evaluated in this study using the International Workshop on CLL (IWCLL) update of the 1996 NCI-Working Group criteria for CLL, which includes assessment of the following: clonal lymphocytes in the peripheral blood by flow cytometry, blood tests for neutrophil count, hemoglobin, and platelet count, CT examination for lymphadenopathy, hepatomegaly, splenomegaly, constitutional symptoms, bone marrow assessment via biopsy/aspirate, and evaluation for disease transformation.

Group	Value	95% CI
All Subjects	12

Progression Free Survival Secondary · From date of study drug initiation until date of progression or death, whichever occurs first, assessed through study completion up to 100 months.

Measured from time of study drug administration to progression or death, measured in months.

Group	Value	95% CI
All Subjects	48	22 – 54

Duration of Response Secondary · From date of end of treatment to progression or death, whichever occurs first, assessed through study completion up to 100 months.

Measured from end of treatment to progression or death, measured in months.

Group	Value	95% CI
All Subjects	70	34 – 85

Time to Response Secondary · From date of study drug initiation to date of initial response, assessed up to 12 months.

Measured from time of study drug administration to initial response (partial or complete), measured in months.

Group	Value	95% CI
All Subjects	10	3 – 12

Overall Survival Secondary · From date of study drug initiation to date of death, assessed through study completion up to 105 months.

Measured from time of study drug administration to death, measured in months.

Group	Value	95% CI
All Subjects	97	13 – 105

Adverse events — posted to ClinicalTrials.gov

Time frame: From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

All Subjects

Serious: 4/14 (29%)

Deaths: 0/14

Serious adverse events (4 terms)

Reaction	System	All Subjects
Pneumonia	Infections and infestations	—
Acute renal insufficiency	Renal and urinary disorders	—
Fever	General disorders	—
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—

Other adverse events (38 terms — click to expand)

Reaction	System	All Subjects
Diarrhea	Gastrointestinal disorders	—
Platelet count decreased	Investigations	—
Neutrophil count decreased	Investigations	—
Anemia	Blood and lymphatic system disorders	—
Neuropathy	Nervous system disorders	—
Lymph node pain	Blood and lymphatic system disorders	—
Rash	Skin and subcutaneous tissue disorders	—
Upper Respiratory infection	Infections and infestations	—
Fever	General disorders	—
Creatinine increased	Investigations	—
Headache	Nervous system disorders	—
Nausea	Gastrointestinal disorders	—
Lymphocyte count increased	Investigations	—
Sinus congestion	Respiratory, thoracic and mediastinal disorders	—
Lymphocyte count decreased	Investigations	—
Aspartate aminotransferase increased	Investigations	—
Dizziness	Nervous system disorders	—
Stomach pain	Gastrointestinal disorders	—
Localized edema	General disorders	—
Hypocalcemia	Metabolism and nutrition disorders	—
Blood bilirubin increased	Investigations	—
Constipation	Gastrointestinal disorders	—
Hypomagnesemia	Metabolism and nutrition disorders	—
Arthralgias	Musculoskeletal and connective tissue disorders	—
Paroxysmal atrial fibrillation	Cardiac disorders	—
Malaise	General disorders	—
Nasal congestion	Respiratory, thoracic and mediastinal disorders	—
White blood cell decreased	Investigations	—
Hypoalbuminemia	Metabolism and nutrition disorders	—
Sinusitis	Infections and infestations	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—
Tumor lysis syndrome	Metabolism and nutrition disorders	—
Intermittent hemorhoidal hemorrhage	Nervous system disorders	—
Allergic reaction	Immune system disorders	—
Back pain	Musculoskeletal and connective tissue disorders	—
Edema Face	General disorders	—
Bone pain	Musculoskeletal and connective tissue disorders	—
Aortic valve disease	Cardiac disorders	—

Most-reported serious reactions: Pneumonia, Acute renal insufficiency, Fever, Breast cancer.

Data from ClinicalTrials.gov NCT01125176 adverse events section.

Sponsor's own description

The investigators' hypothesis is that treatment of CLL with an alternating daily dosing schedule of thalidomide and lenalidomide may result in better tolerability by decreasing each agent's individual toxicities, while preserving efficacy, and therefore lead to a longer duration of therapy and improved responses. Additionally, the combination of the 2 agents may have additive or synergistic effects therapeutically.

In Cycle -1, odd numbered patients will receive oral thalidomide daily days 1-14 followed by no treatment on days 15-28. Even numbered patients will receive oral lenalidomide daily on days 1-14 and then no treatment on days 15-28. Starting with cycle 1, patients will alternate daily thalidomide (every odd day) with daily lenalidomide (every even day) for days 1-28. Rituximab will be given on days 1, 8, 15, and 22 starting with Cycle 1, and then again every 6th cycle thereafter (cycles 7, 13, 19, etc.)

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.