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Lymphoid LeukemiaPhase 2NCT04155840

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

A Phase 2 study testing Copanlisib, Rituximab and Bendamustine in people with Lymphoid Leukemia and Non-Hodgkin's Lymphoma, run by University of Washington at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 65 years and older
What is being tested?
Copanlisib, Rituximab and Bendamustine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteUnited States
Study dates
31 Jan 2020to 16 Mar 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 65 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • 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
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  • 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
  • Previous exposure to other PI3K inhibitors (except copanlisib) is acceptable provided there is no resistance (resistance defined as no response [response defined as partial response (PR) or complete response (CR)]) at any time during therapy, or progressive disease (PD) after any response (PR/CR) or after stable disease within 6 months from the end of the therapy with a PI3K inhibitor
  • Willingness and ability to comply with study and follow-up procedures, and give written informed consent
  • Female subjects of childbearing potential must be surgically sterile, be post-menopausal (per institutional guidelines), or must have a negative serum pregnancy test within 7 days prior to cycle 1 day 1 and agree to use medically acceptable contraception throughout the study period and for 4 months after the last dose of either study drug. Men of reproductive potential may not participate unless they agree to use medically acceptable contraception throughout the study period and for 4 months after the last dose of either study drug
  • Patients must be expected to receive at least 2 cycles of therapy
  • Patients should have an expected survival if untreated of >= 90 days
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (< 3 x ULN for patients with Gilbert-Meulengracht syndrome or for patients with cholestasis due to compressive adenopathies of the hepatic hilum) (collected no more than 7 days before starting study treatment)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (=< 5 x ULN for patients with liver involvement by lymphoma) (no more than 7 days before starting study treatment)
  • Lipase =< 1.5 x ULN (no more than 7 days before starting study treatment)
  • Glomerular filtration rate (GFR) >= 30 mL/min/1.73 m^2 according to the Modification of Diet in Renal Disease (MDRD) abbreviated formula (no more than 7 days before starting study treatment). If not on target, this evaluation may be repeated once after at least 24 hours either according to the MDRD abbreviated formula or by 24 hour sampling. If the later result is within acceptable range, it may be used to fulfill the inclusion criteria instead
  • International normalized ratio (INR) =< 1.5 and partial thromboplastin time (PTT) =< 1.5 x ULN. Prothrombin time (PT) can be used instead of INR if =< 1.5 x ULN (collected no more than 7 days before starting study treatment)
  • Platelet count >= 75,000 /mm^3. For patients with confirmed lymphomatous bone marrow infiltration, platelet count >= 50,000 /mm^3 (collected no more than 7 days before starting study treatment)
  • Hemoglobin (Hb) >= 8 g/dL (collected no more than 7 days before starting study treatment). Packed red blood cell transfusion or erythropoietin should not be given less than 7 days before the exam collection
  • Absolute neutrophil count (ANC) >= 1,000/mm^3 (collected no more than 7 days before starting study treatment). For patients with confirmed lymphomatous bone marrow infiltration, ANC count >= 750/mm^3. Myeloid growth factors should not be given less than 7 days before the exam collection

Who cannot join

  • 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
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  • 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
  • Active, clinically serious infections (> Common Terminology Criteria for Adverse Events [CTCAE] grade 2)
  • Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation
  • Proteinuria of >= CTCAE grade 3 as assessed by a 24 hours (h) total urine protein quantification or estimated by urine protein : creatinine ratio > 3.5 on a random urine sample
  • Unresolved toxicity from prior therapy higher than National Cancer Institute (NCI)-CTCAE grade 1 attributed to any prior therapy/procedure excluding alopecia or sensory neuropathy. Concurrent diagnosis of pheochromocytoma
  • Pregnant or breast-feeding patients. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of treatment, and a negative result must be documented before start of treatment
  • Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study result
  • Congestive heart failure > New York Heart Association (NYHA) class 2
  • Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months)
  • Myocardial infarction less than 6 months before start of test drug
  • Uncontrolled arterial hypertension despite optimal medical management (per investigator's assessment)
  • Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before the start of study treatment
  • Non-healing wound, ulcer, or bone fracture
  • Patients with seizure disorder requiring medication
  • Patients with evidence or history of bleeding diathesis. Any hemorrhage or bleeding event >= CTCAE grade 3 within 4 weeks prior to the start of study treatment
  • Any illness or medical conditions that are unstable or could jeopardize the safety of the patients and their compliance in the study
  • History of having received an allogeneic bone marrow or organ transplant
  • Anti-arrhythmic therapy (beta blockers or digoxin are permitted)
  • Major surgical procedure or significant traumatic injury (as judged by the investigator) less than 28 days before start of treatment, open biopsy less than 7 days before start of treatment
  • Systemic continuous corticosteroid therapy at a daily dose higher than 15 mg prednisone or equivalent is not allowed. Patients may be using topical or inhaled corticosteroids. Previous corticosteroid therapy must be stopped or reduced to the allowed dose at least 7 days performing the screening computed tomography (CT)/magnetic resonance imaging (MRI). If a patient is on chronic corticosteroid therapy, corticosteroids should be de-escalated to the maximum allowed dose before the screening. Patients may be using topical or inhaled corticosteroids
  • Use of CYP3A4 inhibitors and inducers. Copanlisib is primarily metabolized by CYP3A4. Therefore, concomitant use of strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir), and strong inducers of CYP3A4 (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, St. John's wort) are not permitted from day -14 of cycle 1 until the end of treatment visit

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: MRD-Guided Abbreviation of Bendamustine and Rituximab Chemotherapy in Combination With Copanlisib in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

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.

Read the detailed description

This is a dose de-escalation study of copanlisib.

Patients receive copanlisib intravenously (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.

After completion of study treatment, patients are followed up at 14 days, then periodically for up to 3 years.

Being tested
Copanlisib, Rituximab, Bendamustine
Medical subject headings
Leukemia, Lymphoid, Lymphoma, Non-Hodgkin, Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CopanlisibDrug

    Also called 1032568-63-0, BAY 80-6946, PI3K Inhibitor BAY 80-6946

    Given IV

  • RituximabBiological

    Also called C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102

    Given IV

  • BendamustineDrug

    Also called 16506-27-7, SDX-105

    Given IV

Study groups in NCT04155840
Study groupRoleWhat they receive
Treatment (copanlisib, rituximab, bendamustine)ExperimentalPatients 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.
Receives: Drug: Copanlisib; Biological: Rituximab; Drug: Bendamustine

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Will use a Simon optimal two-stage design.

    Measured: End of cycle 4 (each cycle is 28 days)

Secondary outcomes (4)

  1. Marrow MRD-negative Rate

    Measured: At 1 year

  2. Progression Free Survival (PFS)

    Measured: At 1 and 3 years

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

    Measured: End of cycle 4 (each cycle is 28 days)

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

    Measured: Approximately 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Nov 2019
  2. Study start31 Jan 2020
  3. Primary completion16 Mar 2021
  4. Study completion16 Mar 2021

Why it stopped: Terminated due to low accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04155840
Sponsor's protocol ID
RG1005103
Other IDs
NCI-2019-07289, 10325
Status last verified
Apr 2022
First submitted
4 Nov 2019
Last updated
11 Apr 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Copanlisib, Rituximab and Bendamustine in people with Lymphoid Leukemia and Non-Hodgkin's Lymphoma, run by University of Washington at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 11 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Estimate the Marrow Minimal Residual Disease (MRD)-Negative Rate (time frame: End of cycle 4 (each cycle is 28 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04155840.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2022.

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