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Lenalidomide Plus R-CHOP in DLBCL, New Gene Therapies for Hemophilia B , and more

December 30, 2021


David Steensma, MD
Dana-Farber Cancer Institute

A Safety and Tolerability Study of Crenolanib in Combination With Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia Patients With FLT3 Mutations (NCT02283177)

  • Study Design: Non-randomized, open-label, parallel-assignment, safety study
  • Study Start Date: January 2015
  • Estimated Study Completion Date: July 2017
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 48
  • Sponsor: Arog Pharmaceuticals, Inc.

In the Alliance Cooperative Group–led RATIFY trial, the combination of conventional anthracycline/cytarabine induction and cytarabine consolidation with the multi-kinase inhibitor midostaurin was found to improve survival in patients with FLT3-mutant acute myeloid leukemia (AML), compared to chemotherapy without midostaurin. Similarly, the European Sor-AML study showed improved relapse-free survival in AML, including FLT3-mutant AML, when combining the multikinase inhibitor sorafenib with conventional chemotherapy. This study tests a novel FLT3/PDGFR inhibitor, crenolanib, given sequentially during standard induction and consolidation chemotherapy in patients with newly diagnosed AML with FLT3-activating mutations. Crenolanib inhibits both wild-type FLT3 and type 1 mutants.

Study of Orally Administered AG-881 in Patients With Advanced Hematologic Malignancies With an IDH1 and/or IDH2 Mutation (NCT02492737)

  • Study Design: Open-label, single-group assignment, safety/efficacy study
  • Study Start Date: July 2015
  • Estimated Study Completion Date: March 2018
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 50
  • Sponsor: Agios Pharmaceuticals, Inc.

IDH1 or IDH2 mutations are present in 20 to 30 percent of patients with karyotypically normal AML and in a small proportion of patients with MDS and other myeloid neoplasms. AG221 and AG120 are orally available IDH2 and IDH1 inhibitors, respectively, and have induced responses – including complete responses in IDH-mutant AML. The purpose of this phase I, multicenter study is to evaluate the safety, pharmacokinetics, pharmacodynamics, and clinical activity of AG-881, an IDH1/IDH2 inhibitor, in advanced hematologic malignancies that harbor an IDH1 or IDH2 mutation.


Keith Stewart, MBChB, MBA
Mayo Clinic, Arizona

In a phase II study of 64 patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) conducted at Mayo Clinic, lenalidomide combined with RCHOP (R2CHOP) was well tolerated and resulted in a high complete response rate and encouraging progression-free and overall survival. Importantly, the addition of lenalidomide to RCHOP appeared to be particularly beneficial in the non-germinal center B-cell (GCB) subtype of DLBCL compared with historical controls – essentially overcoming the negative prognostic impact of activated B-cell (ABC) phenotype.

These promising results led to the development of randomized front-line studies that will answer questions about the role of R2CHOP in the treatment of patients with newly diagnosed DLBCL. The three trials below investigate lenalidomide combinations with chemoimmunotherapy in aggressive lymphoma, with a particular focus on molecular tumor profiling.

Rituximab and Combination Chemotherapy With or Without Lenalidomide in Treating Patients With Newly Diagnosed Stage II-IV Diffuse Large B Cell Lymphoma (NCT01856192)

  • Study Design: Randomized, open-label, parallel-assignment, efficacy study
  • Study Start Date: August 2013
  • Estimated Study Completion Date: January 2018
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 345
  • Sponsor: National Cancer Institute

This is an NCI-sponsored, multicenter, U.S. Intergroup study led by ECOG that randomizespatients with newly diagnosed stage 2-4 DLBCL to RCHOP or R2CHOP. Patients with all DLBCL subtypes are eligible for inclusion, regardless of molecular subtype, and the study will analyze outcomes based on molecular subtype of DLBCL.

Efficacy and Safety Study of Lenalidomide Plus R-CHOP Chemotherapy Versus Placebo Plus R-CHOP Chemotherapy in Untreated ABC Type Diffuse Large B-Cell Lymphoma (ROBUST) (NCT02285062)

  • Study Design: Randomized, double-blind, parallel-assignment, safety/efficacy study
  • Study Start Date: January 2015
  • Estimated Study Completion Date: September 2022
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 560
  • Sponsor: Celgene Corporation

The ROBUST trial is a multicenter, global study focusing on patients with newly diagnosed ABC DLBCL. Eligible patients with stage 2-4 DLBCL are randomized to R2CHOP or RCHOP plus placebo.

R-ICE and Lenalidomide in Treating Patients With First-Relapse/Primary Refractory Diffuse Large B-Cell Lymphoma (NCT02628405)

  • Study Design: Open-label, single-group assignment, safety/efficacy study
  • Study Start Date: December 2015
  • Estimated Study Completion Date: November 2020
  • Study Status: Not yet open for participant recruitment
  • Estimated Enrollment: 63
  • Sponsor: Academic and Community Cancer Research United (ACCRU)

The promising results in the front-line setting of lenalidomide/chemoimmunotherapy combinations led to the development of a lenalidomide combination as first-line salvage therapy. This newly developed phase I/II study, conducted in the United States through the ACCRU network, adds lenalidomide to RICE (R2ICE) salvage chemotherapy. The single-arm study is open to all patients with a first relapse of DLBCL, regardless of molecular subtype.


Alice Ma, MD
University of North Carolina School of Medicine

Gene therapy for hemophilia was once a theoretical, impractical, pie-in-the-sky dream, but today, thanks to multiple trials of different approaches to delivering the factor IX (and factor VIII, which has lagged behind in trials) genes, it is becoming a reality. Below are a few of the gene therapy trials for hemophilia B. All trials have safety and efficacy as endpoints, with factor IX activity levels being monitored for efficacy and duration of effect.

For more about these trials, visit

A Phase I/II Open-Label, Single Ascending Dose Trial of a Self-Complementing Optimized Adeno-Associated Virus Serotype 8 Factor IX Gene Therapy (AskBio009) in Adults With Hemophilia B (NCT01687608)

A Phase I/II, Open-Label, Non-Randomized, Dose-Escalation Study of SPK-9001 in Subjects With Hemophilia B (NCT02484092)

An Open-Label, Dose-Escalation Study of a Self-Complementary Adeno-Associated Viral Vector (scAAV 2/8-LP1-hFIXco) for Gene Transfer in Hemophilia B (NCT00979238)

Phase I/II Open-Label Safety and Dose-Finding Study of Adeno-Associated Virus (AAV) rh10-Mediated Gene Transfer of Human Factor IX in Adults With Moderate/Severe to Severe Hemophilia B (NCT02618915)


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