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A New Treatment Combination Being Studied for High-Risk CLL

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Medically reviewed by Dr. Brian Koffman

The Bottom Line:

A new phase 1 clinical trial is recruiting patients with relapsed / refractory CLL to test the safety of a combination of RP-3500 and olaparib. This trial is for patients with high-risk genetic alterations such as TP53 mutation, deletion 17p, or deletion 17q.

Who Performed the Research and Where Was it Presented:

Dr. Boyu Hu from Huntsman Cancer Institute and colleagues presented the study design at the American Society for Hematology (ASH) Annual Meeting in 2023.


Patients with specific mutations in their chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) are considered high-risk because they tend to relapse sooner than other patients. Some of the high-risk genetic alterations seen in CLL affect the DNA damage repair pathway, including mutations in tumor suppressor gene TP53 gene, mutations in DNA repair gene ATM, and deletions of parts of chromosomes such as deletion 17p or deletion 11q. RP-3500 and olaparib are two drugs that target the DNA damage repair pathway and have shown promise in solid tumors. A new phase 1 clinical trial is testing if this combination works in patients with CLL.

Methods and Participants:

  • Dr. Hu and colleagues are currently recruiting patients for a phase 1 clinical trial to test the safety of a combination of RP-3500 plus olaparib for patients with relapsed / refractory high-risk CLL who have mutations in DNA damage repair pathways.
  • The primary objectives are to evaluate the safety and tolerability of the combination of RP-3500 and olaparib and to determine the recommended phase 2 dose.
  • Researchers will also evaluate preliminary efficacy in a subset of patients.
  • Researchers plan to enroll 39 patients in the United States.
  • The study will include patients with:
    • Relapsed / refractory CLL or SLL who have had at least two prior lines of therapy and:
      • Have mutations in TP53, ATM, SF3B1, XPO1 or POT1
      • Are positive for deletion 17p or deletion 11q
  • If you are interested in participating, more information can be found here: RP-3500 and Olaparib in DNA Damage Repair Pathway Deficient Relapsed/​Refractory Chronic Lymphocytic Leukemia (CORONADO CLL)


Repurposing drugs already used or studied to treat one type of cancer to be studied in a different cancer is relatively common. We need more options to treat high-risk relapsed / refractory CLL, so this innovative trial is welcomed.

Links and Resources:

Watch the interview on the abstract here:

A New Treatment Combination Being Studied for High-Risk CLL – Dr. Boyu Hu ASH 2023

You can read the actual ASH abstract here: Coronado CLL: A Phase Ib/II Trial of Combination Rp-3500 and Olaparib in DNA Damage Repair Pathway Deficient Relapsed/Refractory Chronic Lymphocytic Leukemia.

Take care of yourself first.

Ann Liu, PhD