What side effects are associated with this type of intervention?

Common treatments for Chronic Lymphocytic Leukemia (CLL) similar to Copanlisib and Nivolumab include kinase inhibitors like acalabrutinib and checkpoint inhibitors. Acalabrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has side effects such as constitutional symptoms, gastrointestinal toxicity, rash, and myelosuppression, with less frequent severe toxicities like syncope, pneumonia, hypertension, atrial fibrillation, neutropenia, and thrombocytopenia. Checkpoint inhibitors, like Nivolumab, can cause immune-related toxicities including pneumonitis, vitiligo, and alopecia, with severe cases being less common.

What prior FDA approvals exist?

For the treatment of Chronic Lymphocytic Leukemia (CLL), the FDA has approved several kinase inhibitors and checkpoint inhibitors. Kinase inhibitors such as ibrutinib and acalabrutinib, which target Bruton tyrosine kinase (BTK), have been approved for CLL due to their efficacy in inhibiting pathways crucial for cancer cell survival. Additionally, venetoclax, a BCL-2 inhibitor, has been approved for its ability to induce apoptosis in CLL cells. In the realm of checkpoint inhibitors, pembrolizumab, an anti-PD-1 antibody, has shown promise in treating various hematologic malignancies, although its use in CLL is more limited compared to solid tumors. These treatments share similarities with copanlisib (a PI3K inhibitor) and nivolumab (an anti-PD-1 antibody), which are being studied for their combined efficacy in treating transformed indolent non-Hodgkin lymphoma and Richter's transformation.

What other types of research exist?

Promising alternatives for CLL treatment in 2024 include Bruton tyrosine kinase (BTK) inhibitors such as acalabrutinib and zanubrutinib, which offer improved tolerability and efficacy. Venetoclax combined with obinutuzumab is another effective option, particularly for achieving undetectable minimal residual disease (MRD). These therapies provide targeted treatment approaches with favorable outcomes for CLL patients.

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PI3K inhibitor

Copanlisib + Nivolumab for Lymphoma

Phase 1

Waitlist Available

Led By Alexey Danilov, MD

Research Sponsored by City of Hope Medical Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) performance status =< 2.

Estimated creatinine clearance (CrCL) using the Cockroft-Gault equation >= 30 mL/min.

Must not have

Evidence of central nervous system (CNS) involvement.

History of allogeneic bone marrow or organ transplant.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 48 weeks

Awards & highlights

Summary

This trial studies how well copanlisib and nivolumab work together in treating patients with aggressive forms of lymphoma. Copanlisib stops cancer cell growth by blocking certain enzymes, and nivolumab helps the immune system attack the cancer. The goal is to find the best dose and see how effective this combination is.

Who is the study for?

This trial is for patients with Richter's transformation or transformed indolent non-Hodgkin lymphoma who've had at least one prior treatment. Participants must have measurable disease, acceptable organ function, and agree to contraception if applicable. Exclusions include pregnancy, uncontrolled health conditions like hypertension or bleeding disorders, recent major surgery, live vaccines, certain heart issues, and previous treatments with similar drugs.

What is being tested?

The trial tests the combination of copanlisib (blocks enzymes for cell growth) and nivolumab (boosts immune system against cancer). It aims to find the best dose and see how well these drugs work together in treating specific types of lymphoma by stopping tumor growth and helping the body attack cancer cells.

What are the potential side effects?

Potential side effects may include reactions related to immune system activation such as inflammation in various organs, infusion-related reactions from drug administration into a vein, fatigue from energy depletion due to treatment effects on normal cells as well as cancerous ones.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can take care of myself and am up and about more than half of my waking hours.

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My kidneys are functioning well enough for treatment.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My cancer has spread to my brain or spinal cord.

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I have had a bone marrow or organ transplant from another person.

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I do not have an uncontrolled bleeding disorder.

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I do not have severe heart issues like recent heart attacks or very weak heart pumping.

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I have a history of HIV.

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I do not have uncontrolled immune-related blood disorders.

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I take more than 15 mg of prednisone daily.

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All my side effects from previous treatments are mild, except for hair loss and nerve pain.

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I am not pregnant or nursing.

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I have a lung condition that affects my breathing.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 48 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 48 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 48 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of adverse events

Incidence of dose-limiting toxicities of copanlisib in combination with nivolumab

Secondary study objectives

Duration of response

Heart rate

Progression-free survival (PFS)

Other study objectives

Tumor response

Side effects data

From 2021 Phase 2 trial • 24 Patients • NCT02631590

75%

Platelet count decreased

75%

Lymphocyte count decreased

71%

Fatigue

71%

White blood cell decreased

67%

Anemia

67%

Neutrophil count decreased

63%

Hypertension

54%

Hyperglycemia

50%

Nausea

46%

Anorexia

46%

Diarrhea

46%

Lipase increased

42%

Alanine aminotransferase increased

42%

Abdominal Pain

33%

Fever

29%

Hyponatremia

25%

Hyperkalemia

25%

Dehydration

25%

Hypotension

25%

Weight loss

25%

Vomiting

25%

Constipation

25%

Rash maculo-papular

21%

Serum amylase increased

21%

Aspartate aminotransferase increased

21%

Edema limbs

17%

Chills

17%

Thromboembolic event

17%

Pain

17%

Alkaline phosphatase increased

17%

Creatinine increased

17%

Sinus tachycardia

17%

Dizziness

13%

Dyspnea

13%

Generalized muscle weakness

13%

Pain in extremity

13%

Hypoalbuminemia

13%

Blood bilirubin increased

13%

Infusion related reaction

13%

Non-cardiac chest pain

13%

Gastrointestinal disorders - Other

13%

Mucositis oral

13%

Sepsis

13%

Upper respiratory infection

13%

Urinary tract infection

13%

Anxiety

13%

Tinnitus

Back pain

Pleural effusion

Neck pain

Insomnia

Gallbladder obstruction

Hypoxia

Ascites

Cough

Bloating

General disorders and administration site conditions -Other

Abdominal distension

Dysphagia

Pruritus

Rash acneiform

Peripheral sensory neuropathy

Infections and infestations - Other

Dysgeusia

Depression

Stomach pain

Blood antidiuretic hormone abnormal

Urine output decreased

Bone pain

Allergic reaction

Hiccups

Sore throat

Paroxysmal atrial tachycardia

Hypercalcemia

Hoarseness

Postnasal drip

Pericarditis

Confusion

Acute kidney injury

Neoplasms benign, malignant and unspecified - Other

Ear pain

Dry eye

Injury, poisoning and procedural complications - Other

Gait disturbance

Atelectasis

Colonic obstruction

Investigations - Other

Phlebitis

Hyperuricemia

Epistaxis

Pneumonitis

Cholecystitis

Gastrointestinal disorders -Other

Pancreatitis

Hypernatremia

Hypomagnesemia

Aspiration

Colitis

Dry mouth

Infusion site extravasation

Toothache

Activated partial thromboplastin time prolonged

Hypokalemia

Nasal congestion

Productive cough

Wheezing

Fracture

Venous injury

Cataract

Hepatic infection

Infections and Infestations - Other

Urinary tract obstruction

Lung infection

Gastroesophageal reflux disease

Malaise

Musculoskeletal and connective tissue disorders - Other

Skin ulceration

Headache

Parathesia

Gallbladder infection

Dry skin

Skin and subcutaneous tissue disorders - Other

Sinus bradycardia

Cystitis noninfective

Hematuria

Renal and urinary disorders - Other

Urine discoloration

100%

80%

60%

40%

20%

Study treatment Arm

Combination Therapy

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (copanlisib and nivolumab)Experimental Treatment2 Interventions

Patients receive copanlisib IV over 60 minutes on days 1, 8, and 15 and nivolumab IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Nivolumab

2014

Completed Phase 3

~5220

Copanlisib

2016

Completed Phase 2

~130

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Chronic Lymphocytic Leukemia (CLL) include kinase inhibitors and checkpoint inhibitors. Kinase inhibitors, such as Copanlisib, block specific enzymes needed for cancer cell growth, leading to cell cycle arrest and apoptosis. Checkpoint inhibitors, like Nivolumab, enhance the immune system's ability to recognize and attack cancer cells by blocking proteins that inhibit immune responses. These targeted therapies are important for CLL patients as they disrupt cancer cell proliferation and boost the immune response, potentially improving treatment outcomes and survival rates.

Targeted therapy in the treatment of chronic lymphocytic leukemia: facts, shortcomings and hopes for the future.New angles of attack in the fight against chronic lymphocytic leukemia: the advent of novel non-chemotherapeutic agents.