Bendamustine and Rituximab in Combination With Copanlisib for the Treatment of Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

NCT04155840 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: RG1005103NCI-2019-0728910325
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This trial studies how well bendamustine and rituximab in combination with copanlisib work in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. Drugs used in chemotherapy, such as bendamustine and rituximab, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Copanlisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving bendamustine and rituximab with copanlisib may work better than bendamustine and rituximab alone in treating chronic lymphocytic leukemia or small lymphocytic lymphoma.

Conditions

Lymphoid Leukemia; Non-Hodgkin's Lymphoma; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (1)

• Estimate the Marrow Minimal Residual Disease (MRD)-Negative Rate

  Will use a Simon optimal two-stage design.

  End of cycle 4 (each cycle is 28 days)

Secondary Outcomes (4)

• Marrow MRD-negative Rate

  At 1 year

• Progression Free Survival (PFS)

  At 1 and 3 years

• MRD Conversion Rate Among Those Who Are MRD-positive After 4 Cycles

  End of cycle 4 (each cycle is 28 days)

• Proportion of Subjects Who Experience Grade 3+ Immune-mediated Adverse Events or Any Grade 5 Adverse Event Possibly Related to Copanlisib

  Approximately 6 months

Study Arms (1)

Treatment (copanlisib, rituximab, bendamustine)

EXPERIMENTAL

Patients receive copanlisib IV over 1 hour on days 1, 8 and 15 or days 1 and 15 (depending on dose level). Patients also receive rituximab IV on day 1 and bendamustine IV on days 1 and 2 of cycles 1-4. Patients who achieve at least a partial response (MRD-positive) continue on treatment for 2 additional cycles. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 7, patients receive copanlisib IV over 1 hour on days 1 and 15 for an additional 6 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Copanlisib; Biological: Rituximab; Drug: Bendamustine

Interventions

Copanlisib DRUG

Given IV

Also known as: 1032568-63-0, BAY 80-6946, PI3K Inhibitor BAY 80-6946

Treatment (copanlisib, rituximab, bendamustine)

Rituximab BIOLOGICAL

Given IV

Also known as: C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, Rituxan, Rituximab ABBS, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar GB241, Rituximab Biosimilar JHL1101, Rituximab Biosimilar SAIT101, RTXM83, Truxima

Treatment (copanlisib, rituximab, bendamustine)

Bendamustine DRUG

Given IV

Also known as: 16506-27-7, SDX-105

Treatment (copanlisib, rituximab, bendamustine)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed, non-17p del chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with any of the three following conditions:
• No prior CLL/SLL directed therapy and Cumulative Illness Rating Scale (CIRS) score \>= 7
• Age \>= 65
• At least one prior CLL/SLL directed therapy with any CIRS score
• CLL/SLL requiring treatment as defined by at least one of the following criteria based on IWCLL 2018 guidelines:
• Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia
• Massive (\> 6 cm below left costal margin), progressive or symptomatic splenomegaly
• Massive nodes (\> 10 cm in longest diameter), or progressive or symptomatic lymphadenopathy
• Progressive lymphocytosis with an increase of \> 50% over a 2-month period or lymphocyte-doubling time of \< 6 months. Lymphocyte-doubling time may be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In patients with initial blood lymphocyte counts of \< 30x10\^9/L (30,000/uL), lymphocyte-doubling time should not be used as a single parameter to define treatment indication. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL/SLL (eg, infection, steroid administration) should be excluded
• Constitutional symptoms, defined as any 1 or more of the following disease-related symptoms or signs:
• Unintentional weight loss of \> 10% within the previous 6 months
• Significant fatigue (ie, inability to work or perform usual activities)
• Fevers \> 100.5 degrees Fahrenheit (F) or 38 degrees Celsius (C) for? 2 weeks without other evidence of infection
• Night sweats for \> 1 month without evidence of infection
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2

You may not qualify if:

• Presence of chromosome 17p deletion, known p53 deletion, or known p53 mutation that impairs normal function
• Prior treatment including systemic therapy or radiotherapy within 21 days of study initiation
• Prior treatment with bendamustine within 2 years
• Prior treatment with copanlisib
• Documented evidence of resistance to prior treatment with idelalisib or other PI3K inhibitors defined as: No response (response defined as partial response \[PR\] or complete response \[CR\]) at any time during therapy, or Progression (PD) after any response (PR/CR) or after stable disease within 6 months from the end of the therapy with a PI3K inhibitor
• Active autoimmune disease or prior autoimmune disease requiring systemic immunosuppression within the past 6 months
• Poorly controlled diabetes mellitus defined as hemoglobin A1c \> 8.5%
• Known lymphomatous involvement of the central nervous system
• Known history of human immunodeficiency virus (HIV) infection. All patients must be screened for HIV up to 28 days prior to study drug start using a blood test for HIV according to local regulations
• Hepatitis B (hepatitis B virus \[HBV\]) or C (hepatitis C virus \[HCV\]) infection. All patients must be screened for HBV and HCV up to 28 days prior to study drug start using the routine hepatitis virus laboratorial panel. Patients positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) will be eligible if they are negative for HBV-deoxyribonucleic acid (DNA), these patients should receive prophylactic antiviral therapy. Patients positive for anti-HCV antibody will be eligible if they are negative for HCV-ribonucleic acid (RNA)
• Previous or concurrent history of malignancies within 3 years prior to study. Any exceptions beyond those listed below must be approved by the principal investigator:
• Cervical carcinoma in situ
• Non-melanoma skin cancer
• Superficial bladder cancer (Ta \[non-invasive tumor\], Tis \[carcinoma in situ\] and T1 \[tumor invades lamina propria\])
• Localized prostate cancer

Sponsors & Collaborators

• University of Washington: lead
• Bayer: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

copanlisib; Rituximab; CT-P10; Bendamustine Hydrochloride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Low accrual precluded statistical analyses and other results analysis.

Results Point of Contact

• Title: Dr. Ryan Lynch
• Organization: University of Washington

rclynch@uw.edu

206-606-1739

Study Officials

• Ryan Lynch

  Fred Hutch/University of Washington Cancer Consortium

  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: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Division of Medical Oncology

Study Record Dates

• First Submitted: November 4, 2019
• First Posted: November 7, 2019
• Study Start: January 31, 2020
• Primary Completion: March 16, 2021
• Study Completion: March 16, 2021
• Last Updated: April 11, 2022
• Results First Posted: April 11, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)