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Phase 1 trial of rituximab, lenalidomide, and ibrutinib in previously untreated follicular lymphoma: Alliance A051103.

Publication ,  Journal Article
Ujjani, CS; Jung, S-H; Pitcher, B; Martin, P; Park, SI; Blum, KA; Smith, SM; Czuczman, M; Davids, MS; Levine, E; Lewis, LD; Smith, SE ...
Published in: Blood
November 24, 2016

Chemoimmunotherapy in follicular lymphoma is associated with significant toxicity. Targeted therapies are being investigated as potentially more efficacious and tolerable alternatives for this multiply-relapsing disease. Based on promising activity with rituximab and lenalidomide in previously untreated follicular lymphoma (overall response rate [ORR] 90%-96%) and ibrutinib in relapsed disease (ORR 30%-55%), the Alliance for Clinical Trials in Oncology conducted a phase 1 trial of rituximab, lenalidomide, and ibrutinib. Previously untreated patients with follicular lymphoma received rituximab 375 mg/m2 on days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 4, 6, 8, and 10; lenalidomide as per cohort dose on days 1 to 21 of 28 for 18 cycles; and ibrutinib as per cohort dose daily until progression. Dose escalation used a 3+3 design from a starting dose level (DL) of lenalidomide 15 mg and ibrutinib 420 mg (DL0) to DL2 (lenalidomide 20 mg, ibrutinib 560 mg). Twenty-two patients were enrolled; DL2 was determined to be the recommended phase II dose. Although no protocol-defined dose-limiting toxicities were reported, a high incidence of rash was observed (all grades 82%, grade 3 36%). Eleven patients (50%) required dose reduction, 7 because of rash. The ORR for the entire cohort was 95%, and the 12-month progression-free survival was 80% (95% confidence interval, 57%-92%). Five patients developed new malignancies; 3 had known risk factors before enrollment. Given the increased toxicity and required dose modifications, as well as the apparent lack of additional clinical benefit to the rituximab-lenalidomide doublet, further investigation of the regimen in this setting seems unwarranted. The study was registered with www.ClinicalTrials.gov as #NCT01829568.

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Published In

Blood

DOI

EISSN

1528-0020

Publication Date

November 24, 2016

Volume

128

Issue

21

Start / End Page

2510 / 2516

Location

United States

Related Subject Headings

  • Thalidomide
  • Survival Rate
  • Rituximab
  • Pyrimidines
  • Pyrazoles
  • Piperidines
  • Middle Aged
  • Male
  • Lymphoma, Follicular
  • Lenalidomide
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ujjani, C. S., Jung, S.-H., Pitcher, B., Martin, P., Park, S. I., Blum, K. A., … Cheson, B. D. (2016). Phase 1 trial of rituximab, lenalidomide, and ibrutinib in previously untreated follicular lymphoma: Alliance A051103. Blood, 128(21), 2510–2516. https://doi.org/10.1182/blood-2016-06-718106
Ujjani, Chaitra S., Sin-Ho Jung, Brandelyn Pitcher, Peter Martin, Steven I. Park, Kristie A. Blum, Sonali M. Smith, et al. “Phase 1 trial of rituximab, lenalidomide, and ibrutinib in previously untreated follicular lymphoma: Alliance A051103.Blood 128, no. 21 (November 24, 2016): 2510–16. https://doi.org/10.1182/blood-2016-06-718106.
Ujjani CS, Jung S-H, Pitcher B, Martin P, Park SI, Blum KA, et al. Phase 1 trial of rituximab, lenalidomide, and ibrutinib in previously untreated follicular lymphoma: Alliance A051103. Blood. 2016 Nov 24;128(21):2510–6.
Ujjani, Chaitra S., et al. “Phase 1 trial of rituximab, lenalidomide, and ibrutinib in previously untreated follicular lymphoma: Alliance A051103.Blood, vol. 128, no. 21, Nov. 2016, pp. 2510–16. Pubmed, doi:10.1182/blood-2016-06-718106.
Ujjani CS, Jung S-H, Pitcher B, Martin P, Park SI, Blum KA, Smith SM, Czuczman M, Davids MS, Levine E, Lewis LD, Smith SE, Bartlett NL, Leonard JP, Cheson BD. Phase 1 trial of rituximab, lenalidomide, and ibrutinib in previously untreated follicular lymphoma: Alliance A051103. Blood. 2016 Nov 24;128(21):2510–2516.

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

November 24, 2016

Volume

128

Issue

21

Start / End Page

2510 / 2516

Location

United States

Related Subject Headings

  • Thalidomide
  • Survival Rate
  • Rituximab
  • Pyrimidines
  • Pyrazoles
  • Piperidines
  • Middle Aged
  • Male
  • Lymphoma, Follicular
  • Lenalidomide