What side effects are associated with this type of intervention?

Treatments for Richter Syndrome, particularly those involving Polatuzumab vedotin combined with chemotherapy agents like rituximab, etoposide, prednisone, cyclophosphamide, and hydroxydaunorubicin, commonly cause side effects such as neutropenia, febrile neutropenia, anemia, thrombocytopenia, gastrointestinal symptoms (nausea, vomiting, diarrhea), fatigue, and infusion-related reactions. Severe but less common side effects can include infections, capillary leak syndrome, and hemolytic uremic syndrome.

What prior FDA approvals exist?

There is limited information on FDA-approved treatments specifically for Richter Syndrome. However, Polatuzumab vedotin, an antibody-drug conjugate targeting CD79b, is being studied in combination with chemoimmunotherapy for this condition. Other treatments for similar lymphoid malignancies include monoclonal antibodies like rituximab, which targets CD20, and combination therapies involving chemotherapeutic agents such as cyclophosphamide and doxorubicin. These therapies aim to target specific antigens on cancer cells and are part of the broader category of targeted treatments for lymphoid cancers.

What other types of research exist?

Promising novel alternatives to Polatuzumab vedotin for Richter Syndrome patients include: 1) Acalabrutinib, a Bruton tyrosine kinase (BTK) inhibitor, which has shown efficacy in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL); 2) Venetoclax, a BCL-2 inhibitor, which has demonstrated significant responses in hematologic malignancies; 3) Zanubrutinib, another BTK inhibitor, which has been effective in CLL/SLL and may offer benefits in Richter Syndrome. These alternatives are based on their mechanisms and recent clinical trial results.

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Alkylating agents

Polatuzumab Vedotin + Chemotherapy for Richter Syndrome

Phase 2

Recruiting

Led By John Allan, M.D.

Research Sponsored by Weill Medical College of Cornell University

Eligibility Criteria Checklist

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

Must have

Subject must have adequate bone marrow function: Absolute neutrophil count of ≥1000 cell/uL, Hemoglobin ≥ 7 g/dL, Platelet count ≥ 30,000 cells/uL

Subject must have an Eastern Cooperative Oncology Group performance status of ≤2

Must not have

Major surgery within 4 weeks before the start of Cycle 1 day 1. Superficial lymph node biopsies or laprascopic lymph node biopsies are exclusionary to this rule.

Subject is known to be positive for HIV

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1.5 years

Awards & highlights

Summary

This trial tests a combination of drugs to treat patients with a severe type of lymphoma. The treatment aims to kill cancer cells and boost the immune system. Patients will be monitored closely for an extended period to see how well they respond.

Who is the study for?

Adults diagnosed with chronic B-cell leukemia or Richter's Syndrome, who have a life expectancy of at least 24 weeks and are in relatively good health (ECOG ≤2). They must have normal organ function and bone marrow activity. Women of childbearing age must use effective contraception, as must men, who should also not donate sperm during the trial.

What is being tested?

The trial is testing Polatuzumab Vedotin combined with chemotherapy drugs (rituximab, etoposide, prednisone, cyclophosphamide, hydroxydaunorubicin) for treating Richter's Transformation. Patients will undergo six cycles of treatment over 21 days each and be monitored weekly until end of treatment followed by long-term follow-ups.

What are the potential side effects?

Possible side effects include reactions to infusion treatments like fever or chills; low blood cell counts leading to increased infection risk; nausea; hair loss from chemotherapy; fatigue; neuropathy which is numbness or tingling in hands and feet; heart issues due to doxorubicin.

Eligibility Criteria

Inclusion Criteria

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

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My blood tests show normal bone marrow function.

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I can perform all self-care but may not be able to work.

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I have CLL that has transformed into DLBCL, confirmed by a biopsy.

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I am 18 years old or older.

Exclusion Criteria

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

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I have not had major surgery in the last 4 weeks, except for minor lymph node biopsies.

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I am HIV positive.

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I have moderate to severe numbness, tingling, or pain in my hands or feet.

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I do not have serious heart conditions like recent heart attacks or unstable heart disease.

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My cancer has spread to my brain or central nervous system.

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I have received treatment for Richter's transformation before.

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My condition is Richter's Transformation, not the DLBCL type.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1.5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1.5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1.5 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Complete metabolic remission/complete remission (CMR/CR) rate of subjects at end of treatment (EOT)

Secondary study objectives

Allogeneic transplantation rate in eligible patients

Overall response rate (ORR)

Overall survival (OS)

+2 more

Side effects data

From 2019 Phase 1 & 2 trial • 231 Patients • NCT01691898

58%

Fatigue

46%

Neuropathy peripheral

42%

Diarrhoea

42%

Nausea

29%

Peripheral sensory neuropathy

29%

Decreased appetite

27%

Asthenia

25%

Neutropenia

25%

Cough

24%

Constipation

22%

Vomiting

20%

Pain in extremity

19%

Abdominal pain

19%

Arthralgia

19%

Dyspnoea

17%

Dizziness

17%

Anaemia

15%

Pyrexia

14%

Hypokalaemia

14%

Back pain

14%

Dyspepsia

14%

Insomnia

14%

Influenza like illness

14%

Oedema peripheral

14%

Headache

12%

Weight decreased

12%

Alopecia

10%

Chest pain

10%

Pruritus

10%

Muscular weakness

10%

Muscle spasms

10%

Hypomagnesaemia

10%

Bone pain

10%

Myalgia

Peripheral motor neuropathy

Dry mouth

Musculoskeletal pain

Anxiety

Neutrophil count decreased

Abdominal pain upper

Chills

White blood cell count decreased

Hyperglycaemia

Hyperhidrosis

Night sweats

Depression

Dehydration

Hypophosphataemia

Memory impairment

Dysuria

Productive cough

Taste Disorder

Tachycardia

Abdominal discomfort

Gait disturbance

Dysgeusia

Hypertension

Rash

Alanine aminotransferase increased

Urinary tract infection

Thrombocytopenia

Hypoaesthesia

Peripheral swelling

Febrile neutropenia

Upper respiratory tract infection

Vision blurred

Abdominal distension

Toothache

Oral candidiasis

Hyponatraemia

Nasal congestion

Dysphonia

Acute kidney injury

Malaise

Fall

Influenza

Gout

Cholecystitis acute

Paraesthesia

Vertigo

Benign neoplasm of skin

Pharyngitis

Pulmonary congestion

Orthostatic hypotension

General physical health deterioration

Abdominal pain lower

Erythema

Contusion

Hernial eventration

Sinusitis

Groin pain

Restless legs syndrome

Syncope

Tremor

Rash erythematous

Rash pruritic

Haematoma

Skin Abrasion

Gastroenteritis viral

Pancreatitis

Rectal haemorrhage

Subileus

Axillary pain

Hepatic steatosis

Hepatocellular injury

Hepatomegaly

Bronchitis

Clostridium difficile infection

Febrile infection

Lung disorder

Hypotension

Lymphadenopathy

Ear discomfort

Visual impairment

Pain

Oesophageal candidiasis

Aspartate aminotransferase increased

Blood creatinine increased

Platelet count decreased

Hypercalcaemia

Hyperuricaemia

Hypoxia

Dermatitis acneiform

Nasopharyngitis

Infusion related reaction

Epistaxis

Chest discomfort

Fistula of small intestine

100%

80%

60%

40%

20%

Study treatment Arm

Arm B (FL+DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab

Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab

Cohort E (FL+DLBCL): Obinutuzumab + Polatuzumab

Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab

Arm A (FL+DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab

Cohort C (FL): RTX + Polatuzumab

Trial Design

1Treatment groups

Experimental Treatment

Group I: Polatuzumab vedotin plus R-EPCHExperimental Treatment6 Interventions

Polatuzumab vedotin will be given in conjunction with 6 cycles of R-EPCH (rituximab, etoposide, prednisone, cyclophosphamide, hydroxydaunorubicin). The dosing schedule and regimen for R-EPCH will follow established protocols. Polatuzumab vedotin will be administered on Day 1 of each 21-day cycle.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Etoposide

2010

Completed Phase 3

~2960

Prednisone

2014

Completed Phase 4

~2500

Cyclophosphamide

2010

Completed Phase 4

~2320

Polatuzumab Vedotin

2019

Completed Phase 2

~820

Rituximab

1999

Completed Phase 4

~2200

0 / 11Eligibility 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

Polatuzumab vedotin is an antibody-drug conjugate that targets CD79b, a protein expressed on the surface of B cells, including those involved in Richter Syndrome. By binding to CD79b, Polatuzumab vedotin delivers a cytotoxic agent directly to the cancer cells, leading to their destruction. This targeted approach helps to minimize damage to healthy cells. In combination with chemotherapy agents like rituximab, etoposide, prednisone, cyclophosphamide, and hydroxydaunorubicin, the treatment aims to enhance the overall anti-cancer effect by attacking the cancer cells through multiple mechanisms. This is crucial for Richter Syndrome patients, as the disease is aggressive and often resistant to standard therapies, necessitating a robust and multifaceted treatment strategy.