venetoclax for Lymphoma

Phase-Based Estimates
1
Effectiveness
2
Safety
Malopolskie Centrum Medyczne /ID# 1142-0364, Krakow, Poland
Lymphoma+5 More
venetoclax - Drug
Eligibility
18+
All Sexes
Eligible conditions
Lymphoma

Study Summary

This study is evaluating whether a combination of ibrutinib and venetoclax can be used to treat chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

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Eligible Conditions

  • Lymphoma
  • Leukemia, Lymphoid
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia
  • Chronic Lymphocytic Leukemia (CLL)
  • Small Lymphocytic Lymphoma

Treatment Effectiveness

Study Objectives

This trial is evaluating whether venetoclax will improve 5 primary outcomes and 24 secondary outcomes in patients with Lymphoma. Measurement will happen over the course of Baseline, and last post-baseline value on or prior to venetoclax first dose date (cycle 4 day 1) or, for participants who never received venetoclax, the post-baseline value closest to cycle 4 day 1 (i.e. 84 days after the first dose date of ibrutinib)..

1 year after randomization
MRD Cohort: 1-Year Disease-Free Survival (DFS) Rate in Confirmed uMRD Randomized Participants
Day 84
FD Cohort: TLS Risk Reduction Rate With 3-Cycle Ibrutinib Lead-In (Percentage of Participants No Longer High Risk After 3-cycle Lead-in)
MRD Cohort: Tumor Lysis Syndrome (TLS) Risk Reduction Rate With 3-Cycle Ibrutinib Lead-In (Percentage of Participants No Longer High Risk After 3-cycle Lead-in)
Day 6
MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Apparent Total Clearance at Steady-State (CLss/F)
MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Area Under the Plasma Concentration-Time Curve (AUC) Over the Last 24-hour Dosing Interval (AUC0-24h); AUC From Time Zero to the Time of Last Quantifiable Concentration (AUClast)
MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Terminal Elimination Rate Constant (λz)
MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Time to Cmax (Tmax); Time of Last Measurable Concentration (Tlast); Terminal Elimination Half-Life (t1/2,Term)
MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: AUC0-24h
MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: CLss/F
MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: Cmax
MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: Tmax
MRD Cohort: Pharmacokinetics (PK) of Ibrutinib When Dosed in Combination With Venetoclax: Observed Maximum Concentration (Cmax)
Month 3
FD Cohort: Percentage of Participants With TEAEs, Treatment-Emergent SAEs, and Discontinuations Due to TEAEs
Month 7
MRD Cohort: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs
Month 9
FD Cohort: DOR
Month 2
MRD Cohort: Duration of Response (DOR)
Month 9
FD Cohort: MRR
Month 2
MRD Cohort: MRD-Negativity Rate (MRR)
Month 2
MRD Cohort: CRR (CR/CRi Rate)
MRD Cohort: Overall Response Rate (ORR)
Month 2
MRD Cohort: Kaplan-Meier Estimate of Overall Survival (OS) Rate at 36 Months Landmark Time
Month 9
FD Cohort: Kaplan-Meier Estimate of PFS Rate at 24 Months Landmark Time
Month 2
MRD Cohort: Kaplan-Meier Estimate of Progression Free Survival (PFS) Rate at 36 Months Landmark Time
Month 9
FD Cohort: Complete Response Rate (CRR; Complete Response/Complete Response With Incomplete Blood Count Recovery [CR/CRi]) Rate
FD Cohort: ORR
Month 9
FD Cohort: Kaplan-Meier Estimate of OS Rate at 24 Months Landmark Time
approximately 24 months
Complete Response Rate
approximately 40 months
Disease free survival
MRD-negative response rate

Trial Safety

Safety Estimate

2 of 3
This is better than 68% of similar trials

Trial Design

10 Treatment Groups

MRD Cohort Randomized Placebo to match ibrutinib (blinded)
MRD Cohort Randomized open-label ibrutinib
Placebo group

This trial requires 323 total participants across 10 different treatment groups

This trial involves 10 different treatments. Venetoclax is the primary treatment being studied. Participants will be divided into 8 treatment groups. Some patients will receive a placebo treatment. The treatments being tested are in Phase 2 and have already been tested with other people.

MRD Cohort Randomized open-label ibrutinibSubjects will receive 420 mg capsules of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization. Subjects that are MRD-positive will be randomized to receive ibrutinib 420 mg capsules orally once daily on a continuous scheduled until clinical disease progression or unacceptable toxicity.
MRD Cohort Randomized open-label ibrutinib + venetoclaxSubjects will receive 420 mg capsules of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization. Subjects that are MRD-positive will be randomized to receive ibrutinib 420 mg capsules and venetoclax 400 mg tablets orally once daily on a continuous schedule until clinical disease progression or unacceptable toxicity.
MRD Cohort/Confirmed Undetectable MRD (uMRD): Randomized to Ibrutinib (Blinded)Participants receive 420 mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre-randomization phase). Participants with confirmed uMRD are randomized to receive ibrutinib 420 mg orally once daily on a continuous schedule until MRD-positive relapse, disease progression (PD), or unacceptable toxicity. After MRD-positive relapse or disease progression (PD) by iwCLL criteria, participants can reintroduce 400 mg venetoclax with a 5-week ramp up. If venetoclax is to be reintroduced, venetoclax treatment is to continue at the dose of 400 mg/day for up to approximately 2 years (cumulative) until PD or unacceptable toxicity.
MRD Cohort Randomized ibrutinib (blinded)Subjects will receive 420 mg capsules of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization. Subjects that are MRD-negative will be randomized to receive ibrutinib 420 mg capsules orally once daily on a continuous schedule until clinical disease progression or unacceptable toxicity
Fixed Duration Cohort - Open Label ibrutinib + venetoclaxSubjects will receive 420 mg capsules of single agent ibrutinib for first 3 cycles followed by ibrutinib plus venetoclax combination treatment for 12 cycles (a cycle is defined by 28 days) or until disease progression or unacceptable toxicity.
MRD Cohort/uMRD Not Confirmed: Randomized to Ibrutinib (Open-Label)Participants receive 420 mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre randomization phase). Participants with uMRD not confirmed are randomized to receive open-label ibrutinib 420 mg orally once daily on a continuous schedule until PD or unacceptable toxicity. In case of confirmed PD after restaging per iwCLL criteria, participants can continue ibrutinib and reintroduce venetoclax treatment. If venetoclax is to be reintroduced, venetoclax treatment is to continue at the dose of 400 mg/day for up to approximately 2 years (cumulative) until PD or unacceptable toxicity.
MRD Cohort/uMRD Not Confirmed: Randomized Ibrutinib + Venetoclax (Open-Label)Participants receive 420 mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre randomization phase). Participants with uMRD not confirmed are randomized to receive open-label ibrutinib 420 mg and venetoclax 400 mg orally once daily on a continuous schedule until PD or unacceptable toxicity. Venetoclax was allowed for administration up to 2 years cumulatively from first dose started in the pre-randomization phase to last dose in the randomization phase.
Fixed Duration (FD) Cohort: Open Label Ibrutinib + VenetoclaxParticipants receive 420 mg of single-agent ibrutinib for first 3 cycles followed by ibrutinib plus venetoclax combination treatment (ibrutinib 420 mg and venetoclax 400 mg orally once daily on a continuous schedule) for 12 cycles (a cycle is defined by 28 days) or until disease progression or unacceptable toxicity.
MRD Cohort Randomized Placebo to match ibrutinib (blinded)Subjects will receive 420 mg capsules of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization. Subjects that are MRD-negative will be randomized to receive matching ibrutinib placebo capsules orally once daily on a continuous schedule until MRD-positive relapse, clinical disease progression or unacceptable toxicity.
MRD Cohort/Confirmed uMRD: Randomized Placebo (Blinded)Participants receive 420 mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre-randomization phase). Participants with confirmed uMRD are randomized to receive placebo orally once daily on a continuous schedule until MRD-positive relapse, PD or unacceptable toxicity. If MRD-positive relapse or PD is confirmed after restaging per iwCLL criteria, participants can first reintroduce oral daily ibrutinib with the option of subsequently reintroducing 400 mg venetoclax with a 5-week ramp up, if subsequent disease relapse per iwCLL criteria occurs after ibrutinib reintroduction. If venetoclax is to be reintroduced, venetoclax treatment is to continue at the dose of 400 mg/day for up to approximately 2 years (cumulative) until PD or unacceptable toxicity.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Venetoclax
FDA approved
Ibrutinib
FDA approved

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: from the first dose of ibrutinib to time of death. overall median follow-up time was 27.9 months at the time of the primary analysis (data cutoff date: 15 december 2020).
This trial has the following approximate timeline: 3 weeks for initial screening, variable treatment timelines, and roughly from the first dose of ibrutinib to time of death. overall median follow-up time was 27.9 months at the time of the primary analysis (data cutoff date: 15 december 2020). for reporting.

Closest Location

Site Reference ID/Investigator# 0071 - Louisville, KY

Eligibility Criteria

This trial is for patients born any sex aged 18 and older. You must have received newly diagnosed for Lymphoma or one of the other 5 conditions listed above. There are 7 eligibility criteria to participate in this trial as listed below.

Mark “yes” if the following statements are true for you:
The person has chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) that meets the diagnostic criteria set by the International Workshop on CLL (IWCLL), with active disease meeting at least 1 of the criteria set by the IWCLL for requiring treatment. show original
The absolute neutrophil count is greater than 750/µL. show original
This person has an abnormally high platelet count. show original
Hemoglobin levels above 8.0 g/dL are indicative of anemia. show original
Measurable nodal disease by computed tomography (CT)
are required for methotrexate Methotrexate requires adequate hepatic and renal function in order to be effective. show original
Adequate hematologic function

Patient Q&A Section

Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

How many people get lymphoma a year in the United States?

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Around 25,000 people develop a nonneoplastic malignancy (lymphoma, leukemia, or myeloma) every year. Because lymphoma was found to be the most prevalent malignancy (11.3%) among those with nonneoplastic malignancies, it is prudent to evaluate for lymphoma and to undertake tests for HIV and hepatitis B in those who are at increased risk of lymphoma. A greater understanding of the causes, epidemiology, and clinical course of lymphomas is required in order to better guide therapy and to improve clinical outcomes.

Unverified Answer

What causes lymphoma?

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Immunosuppressant or cytotoxic agents (carcinoma). \nLymphocyte infiltrate and/or tumor necrosis. \nTumors and nontumorous cells cause inflammation. \nTumor infiltrates lymphocytes.\n\nThe cause of most common types of lymphoma in dogs including canine diffuse B-cell lymphoma are unknown. However, one study has indicated an increased risk of developing lymphoma in dogs who use nonsteroidal corticosteroids. More research is needed in elucidating the role of corticosteroids in this disease process.

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Can lymphoma be cured?

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The cure rate for lymphoma is about 15%. To be cured the disease has to be free from symptoms for a long time, but there is no way to know this on the basis of what patients say about their symptoms or what they do about the symptoms, and so in practice there is no way to know how soon the disease can be cured. What is true, however, is that when a cure is found for cancer, and the person is fully cured, then there is no further risk from cancer. The risk of cancer remains higher because cancer is still an ongoing disease that can reappear.

Unverified Answer

What are the signs of lymphoma?

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Symptoms of lymphoma vary depending on the type of lymphoma. For example, there are a number of signs and symptoms of low CD4 and HIV coinfection in patients with AIDS lymphoma, or high-grade B-cell lymphoma with a low-grade form of an immune deficiency. It is important to consider the possible range of possible symptoms and signs as well as take into account the stage of lymphoma when presenting cases to general practitioners.

Unverified Answer

What is lymphoma?

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Most cancers begin in a single cell and then, over time, spread to other parts of the body. As lymphoma develops it most commonly starts in the lymph systems. If found early, lymphoma can often be treated for a long time with good results. theme: palliative care question: What is palliative care?\nThe term palliative care, referring to an integrated approach to the care of people with life-limiting and challenging diseases, was introduced in 1984, with a definition of providing care in the last 12 weeks of life.\n

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What are common treatments for lymphoma?

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A variety of treatments are utilized to cure patients with lymphoma. Chemotherapy has been the most effective treatment for lymphoma for many decades. Radiation therapy is also sometimes used to treat lymphoma. However, the effectiveness of radiation therapy in treating lymphoma remains an area of active research. Lymphoma patients can develop a multitude of secondary cancers following treatment and are at risk for secondary cancers of the skin, intestines, lungs, breasts, and testes. Treatment for lymphoma is sometimes discontinued rather than restart when a patient progresses beyond remission.

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Does venetoclax improve quality of life for those with lymphoma?

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In this preliminary study on a cohort of patients with lymphoma, venetoclax as a first-line treatment was generally well-tolerated and associated with improvements in both health utility and cognitive functioning, with no significant increase in toxicity.

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Is venetoclax typically used in combination with any other treatments?

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Recent findings of this pooled analysis show that venetoclax in a first-line or second-line setting alone is associated with similar overall responses compared with venetoclax as a second-line agent in combination with brentuximab or a combination involving rituximab and a VEGF inhibitor.

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Has venetoclax proven to be more effective than a placebo?

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In this large multi-center, multicenter phase 3 study, superiority of venetoclax was demonstrated in relapsed or refractory [follicular lymphoma](https://www.withpower.com/clinical-trials/follicular-lymphoma) (FL) or diffuse large B-cell lymphoma (DLBCL) patients with follicular lymphoma (FL) who previously received at least two prior therapies. There were no serious side effects and no grade ≥ 3 adverse effects. In addition, in FL patients, responses with venetoclax continued when treatment was completed. Data from a recent study support venetoclax as a novel and effective treatment option in relapsed or refractory FL patients.

Unverified Answer

How does venetoclax work?

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Venetoclax treatment induced an effective anti-tumor effect in NHL pre-selected for high expression levels of the BCL-2 protein. We have thus characterized a selective inhibitor of the BCL-2 pathway that holds great potential for further exploration in combination with currently used anti-NHL regimens.

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How quickly does lymphoma spread?

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[ TL;DR available at the bottom. An MRI showed minimal evidence of disease spread over the five-year interval. This was despite the presence of lesions larger than 2 centimeters in the neck and arm, as well as other areas. I am still cancer-free. (Note that most small lymphomas do not require treatment and will eventually regress; my current NHL diagnosis is a small B-cell lymphoma.) ] When the diagnosis was made in May 1999, it was a fast-growing disease. During the five-year period of this story, there were some very hard facts. My tumors would grow a lot faster in the years following the diagnosis. The disease kept coming back in waves.

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