Intermittent Duvelisib Dosing in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

NCT03961672 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 6 other identifiers: 19563NCI-2019-02789HEM-19009-LM19563 (City of Hope)STUDY00019402P30CA033572
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial studies how well duvelisib on an intermittent (irregular) dosing schedule works in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. Duvelisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving duvelisib on an intermittent schedule may result in similar effectiveness with less amount of severe side effects.

Conditions

Refractory Chronic Lymphocytic Leukemia; Refractory Small Lymphocytic Lymphoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) at 12 Months

  Progression is defined using IWCLL 2018 guidelines (Section 5.3 of Hallek et al, 2018). Proportion of subjects achieving 12-month PFS were estimated along with a two-sided exact Clopper-Pearson 95% confidence interval. PFS was estimated from start of duvelisib treatment until death, time of progression, start of new therapy, or end of follow-up, whichever occurs first. PFS was censored at the start of new therapy or end of follow-up, whichever occurs first.

  First dose of duvelisib until death, time of progression, start of new therapy, or 12 months from start of therapy, whichever occurs first

Secondary Outcomes (5)

• Objective Response Rate (ORR) (Including Complete Response [CR] and Partial Response [PR])

  First dose of duvelisib up to 12 months after discontinuation of duvelisib

• Median Progression-Free Survival (PFS)

  First dose of duvelisib until death, time of progression, or start of new therapy, whichever occurs first, assessed up to 12 months after discontinuation of duvelisib

• Percentage of the Participants With 12-month Duration of Response (DOR)

  From time of ORR until death, time of progression, start of new therapy, or end of follow-up, whichever occurs first, assessed up to 12 months after discontinuation of duvelisib

• Percentage of Participants With Grade 3 4 5 Toxicity Related to Duvelisib

  From first dose of duvelisib until 3 months post-discontinuation of duvelisib

• Number of Administrated Cycles of the Study Treatment

  From first dose of duvelisib until time of duvelisib discontinuation up to 5 years.

Study Arms (1)

Treatment (duvelisib)

EXPERIMENTAL

INDUCTION: Patients receive duvelisib PO BID on days 1-28. Cycles repeat every 28 days for 12 weeks in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive duvelisib PO BID on days 1-2, 8-9, 15-16, and 22-23. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Duvelisib

Interventions

Duvelisib DRUG

Given PO

Also known as: 8-Chloro-2-phenyl-3-((1S)-1-(7H-purin-6-ylamino)ethyl)isoquinolin-1(2H)-one, Copiktra, INK-1197, IPI-145

Treatment (duvelisib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent document.
• Histologically or flow cytometry confirmed diagnosis of B-CLL/small lymphocytic lymphoma (SLL) according to National Cancer Institute - Working Group (NCI-WG) 1996 guidelines. Patients who lack CD23 expression on their leukemia cells should be examined for (and found NOT to have) either t(11;14) or cyclin D1 overexpression, to rule out mantle cell lymphoma.
• Participants have undergone \>= 1 prior chemotherapy-based or immunotherapy-based regimen or targeted therapy (e.g., inhibitors of BTK \[e.g., ibrutinib\], or BCL2 \[e.g., venetoclax\]) administered for \>= 2 cycles (\>= 8 weeks for oral therapies), and have had either documented disease progression or no response (i.e., stable disease \[SD\]) to the most recent treatment regimen.
• Note: Individuals intolerant to ibrutinib therapy and those who progress on ibrutinib are eligible as long as they satisfy the above criteria.
• Patients with CLL/SLL must demonstrate active disease meeting at least 1 of the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria for requiring treatment:
• A minimum of any one of the following constitutional symptoms:
• Unintentional weight loss \> 10% within the previous 6 months prior to screening.
• Extreme fatigue (unable to work or perform usual activities).
• Fevers of greater than 100.5 degrees Fahrenheit (F) for \>= 2 weeks without evidence of infection.
• Night sweats without evidence of infection.
• Evidence of progressive marrow failure as manifested by the development of, or worsening of anemia or thrombocytopenia.
• Massive (i.e., \> 6 cm below the left costal margin), progressive or symptomatic splenomegaly.
• Massive nodes or clusters (i.e., \> 10 cm in longest diameter) or progressive lymphadenopathy.
• Progressive lymphocytosis with an increase of \> 50% over a 2-month period, or an anticipated doubling time of less than 6 months.
• Autoimmune anemia or thrombocytopenia that is poorly responsive to corticosteroids.

You may not qualify if:

• Prior therapeutic intervention with any of the following:
• Therapeutic anticancer antibodies within 4 weeks;
• Radio- or toxin-immunoconjugates within 10 weeks;
• Inhibitors of Bruton tyrosine kinase (BTK) (e.g., ibrutinib), BH3-mimetic venetoclax, lenalidomide and other "targeted" therapy - within 6 half-lives (i.e., 36 hours for ibrutinib)
• All other chemotherapy, radiation therapy within 3 weeks prior to initiation of therapy.
• PI3K inhibitors (idelalisib, copanlisib or any investigational PI3K inhibitor including duvelisib and umbralisib) at any time.
• Any adverse event related to prior therapy that has not recovered to grade =\< 1.
• Chronic use of corticosteroids in excess of prednisone 30 mg/day or its equivalent.
• Allogeneic stem cell transplant within the past 12 months, or ongoing immunosuppressive therapy other than prednisone =\< 10 mg/day (or equivalent).
• Use of strong CYP3A4 inhibitors or inducers, in the one week prior to initiating study treatment or concomitant.
• Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), or herpes zoster (varicella zoster virus \[VZV\]) at screening.
• History of prior malignancy except:
• Malignancy treated with curative intent and no known active disease present for \>= 2 years prior to initiation of therapy on current study;
• Adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in situ) without evidence of disease;
• Adequately treated in situ carcinomas (e.g., breast, cervical, esophageal, etc.) without evidence of disease;

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

duvelisib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Alexey Danilov, MD
• Organization: City of Hope Medical Center

adanilov@coh.org

626-359-8111

Study Officials

• Alexey V Danilov

  City of Hope Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2019
• First Posted: May 23, 2019
• Study Start: May 13, 2020
• Primary Completion: July 31, 2023
• Study Completion (Estimated): October 26, 2026
• Last Updated: January 5, 2026
• Results First Posted: August 7, 2024

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)