Venetoclax + BEAM Conditioning for Lymphoma

Not currently recruiting at 1 trial location

Overseen By Allison Winter, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Case Comprehensive Cancer Center

Must not be taking: Antiretrovirals, CYP3A4 modulators

Disqualifiers: Pregnancy, HIV, Metastatic cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for Non-Hodgkin Lymphoma (NHL) by adding Venetoclax, a targeted therapy, to a standard chemotherapy regimen before a stem cell transplant. Venetoclax targets a protein in cancer cells, aiding in their destruction. The trial seeks to determine the safest dose and assess whether this combination can improve remission rates, where cancer symptoms decrease or disappear. It is suitable for those with NHL who have tried other treatments and are considering a stem cell transplant as their best option. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial, especially if they interact with Venetoclax. If you are on medications that affect the CYP3A4 enzyme or P-gp, a 7-day break from these drugs is required before starting Venetoclax. It's important to discuss your current medications with the trial team to see if any changes are needed.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research is investigating whether Venetoclax, combined with BEAM chemotherapy drugs, is safe for individuals with Non-Hodgkin Lymphoma (NHL). Although the FDA has approved Venetoclax for a different cancer, it is not yet approved for NHL or in combination with BEAM.

Previous studies have explored the side effects and optimal dose of Venetoclax when added to BEAM. These studies are ongoing, with the primary goal of assessing treatment tolerability, particularly before a stem cell transplant. As a Phase 1 trial, the focus is on safety and determining the correct dose, indicating that the treatment is in the early testing stages for NHL. Researchers are closely monitoring patient responses.

Currently, detailed safety information for NHL patients is lacking. However, since Venetoclax is approved for another condition, some safety data about the drug is available. This study aims to determine its safety when combined with BEAM for NHL. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the Venetoclax + BEAM conditioning treatment for lymphoma because it introduces Venetoclax, which specifically targets and inhibits B-cell lymphoma 2 (BCL-2) proteins. This is unique because most existing treatments, like R-CHOP or ICE regimens, don't directly target this protein, which is crucial for cancer cell survival. Additionally, the treatment uses a novel dose escalation approach with increasing duration rather than dosage, potentially improving safety and effectiveness. By integrating Venetoclax with the established BEAM chemotherapy regimen, this treatment aims to enhance the elimination of cancer cells while minimizing harm to the patient.

What evidence suggests that Venetoclax + BEAM could be an effective treatment for Non-Hodgkin Lymphoma?

This trial will evaluate the combination of Venetoclax with BEAM chemotherapy for Non-Hodgkin Lymphoma (NHL). Studies have shown that adding Venetoclax to BEAM might be promising, as this combination blocks a protein called Bcl-2, which helps cancer cells survive. By blocking Bcl-2, Venetoclax can help kill cancer cells. Research has indicated that Venetoclax has already been effective for some blood cancers, like chronic lymphocytic leukemia (CLL), and there is hope it can improve outcomes for NHL as well. Early findings suggest that this combination might increase the chance of remission when used before stem cell transplants. ^{1 2 3 6 7}

Who Is on the Research Team?

Allison Winter, MD

Principal Investigator

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for people with Non-Hodgkin Lymphoma who've had at least one prior treatment. They must have certain blood cell counts, normal organ function, and not be pregnant or breastfeeding. People with severe allergies to Venetoclax or similar drugs, unresolved treatment toxicities, uncontrolled illnesses, HIV on antiretrovirals, recent major surgery, or using certain medications can't join.

Inclusion Criteria

I do not have active Hepatitis B according to my test results.

I am in remission or my disease is stable, and I am recommended for autologous transplantation.

I have Non-Hodgkin Lymphoma and have undergone at least one treatment like CHOP or R-CHOP.

Exclusion Criteria

Patients who have not recovered from adverse events due to agents administered more than 2 weeks earlier, Prior treatment toxicities have not resolved to ≤ Grade 2 according to NCI CTCAE Version 5.0 (except clinically unrelated toxicities such as alopecia or peripheral neuropathy), Patients receiving any other investigational agents, History of allergic reactions attributed to compounds of similar chemical or biologic composition to Venetoclax or other agents used in this study, Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, Patients who are pregnant or breastfeeding will be excluded from this study because carmustine, etoposide, cytarabine, and melphalan are chemotherapeutic agents with the potential for teratogenic or abortifacient effects, HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Venetoclax, Malabsorption syndrome or other condition that precludes enteral route of Venetoclax administration, Patients with metastatic solid tumor malignancies, Major surgery, other than diagnostic surgery, within 2 weeks, Medical condition requiring chronic use of high dose systemic corticosteroids (i.e., doses of prednisone higher than 10 mg/day or equivalent), Patients with chronic use of moderate or strong CYP3A4 modulators (inhibitor or inducer) or use of a P-gp inhibitor, or a P-gp substrate with a narrow therapeutic index are prohibited, Concomitant medications that could potentially lead to adverse reactions and should be considered cautionary

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning and Treatment

Participants receive Venetoclax in combination with BEAM chemotherapy prior to Autologous Stem Cell Transplant (ASCT)

1 cycle (approximately 1 week)

Inpatient stay for conditioning and ASCT

Autologous Stem Cell Transplant (ASCT)

Infusion of previously collected autologous stem cells following V+BEAM therapy

Immediate post-conditioning

Inpatient stay for ASCT

Follow-up

Participants are monitored for safety, engraftment, and survival outcomes

24 months

Follow-up visits at 3, 6, 12, 18, and 24 months post-discharge

What Are the Treatments Tested in This Trial?

Interventions

• Venetoclax

Trial Overview The study tests adding Venetoclax to BEAM chemotherapy before a stem cell transplant in NHL patients. The goal is to find the right dose and check safety. Venetoclax targets a protein that helps cancer cells survive; it's approved for leukemia but investigational here.

How Is the Trial Designed?

Group I: Venetoclax+BEAM x 1 cycle prior to ASCT Experimental Treatment 1 Intervention

Venetoclax dose escalation cohorts + BEAM (Carmustine, Etoposide, Cytarabine, Melphalan) begin with dose level 1 (800mg on Day -7 and Day -6). The dosing cohorts are escalated in a 3 + 3 design but with increasing duration instead of increasing dosage. Carmustine 300 mg/m2 by IV over 2 hours on Day -7. Etoposide 100 mg/m2 by IV over 6 hours daily for 4 consecutive days, Day-6 through Day-3. Cytarabine 200 mg/m2 by IV over 2 hours every 12 hours for 3 consecutive days, Day-6 through Day-4. Melphalan 140 mg/m2 by IV over 30 minutes or IV push once on Day -2. Following V+BEAM therapy, participants will receive Autologous Stem Cell Transplant (ASCT): infusion of previously collected autologous stem cells and supportive care per institutional guidelines

Who Is Running the Clinical Trial?

Case Comprehensive Cancer Center

Lead Sponsor

Trials

472

Recruited

33,400+

Published Research Related to This Trial

In a study of 23 patients with aggressive B-cell non-Hodgkin lymphoma, the combination of rituximab with CODOX-M/IVAC showed promising efficacy, with 83% of low-risk and 71% of high-risk patients achieving complete remission after treatment.

The safety profile was acceptable, with no treatment-related deaths and manageable toxicity, including only two cases of grade 3 neutropenia, suggesting that this treatment combination is both effective and safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in combination with CODOX-M/IVAC: a retrospective analysis of 23 cases of non-HIV related B-cell non-Hodgkin lymphoma with proliferation index >95%. Mohamedbhai, SG., Sibson, K., Marafioti, T., et al.[2015]

Venetoclax is an effective and well-tolerated treatment for advanced hematological malignancies, particularly in patients with chronic lymphocytic leukemia, showing a satisfactory overall event rate of 73%.

The most common adverse events associated with venetoclax include nausea, diarrhea, and thrombocytopenia, but these are generally mild and manageable, with few cases of severe complications like tumor lysis syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Bcl-2 Inhibitor Venetoclax in Hematological Malignancy: A Systematic Review and Meta-Analysis of Clinical Trials. Li, Q., Cheng, L., Shen, K., et al.[2020]

In a retrospective study of 34 adult patients with various types of non-Hodgkin lymphoma treated off-label with venetoclax, the overall response rate was 26%, indicating modest efficacy in heavily pretreated patients.

Adverse events occurred in 76% of patients, with higher incidence than reported in clinical trials, highlighting the need for further investigation into the safety and dosing strategies of venetoclax in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Patients With Relapsed/Refractory Non-Hodgkin Lymphoma With Venetoclax: A Single-Center Evaluation of Off-Label Use. Hughes, ME., Landsburg, DJ., Rubin, DJ., et al.[2020]

Venetoclax is a highly effective treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), achieving response rates of about 80% in clinical trials involving 240 patients from 2011 to 2016.

While venetoclax has an acceptable safety profile, common side effects include neutropenia and diarrhea, and there is a risk of tumor lysis syndrome (TLS), which can be managed through careful dose ramp-up and patient education, leading to no reported TLS events in ongoing trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . Brumbaugh Paradis, H., Alter, D., Llerandi, D.[2018]

Venetoclax is an oral medication that selectively inhibits the BCL-2 protein, which helps cancer cells survive, thereby restoring the ability of these malignant cells to undergo programmed cell death (apoptosis).

It has been approved in the USA for treating chronic lymphocytic leukaemia (CLL) in patients with a specific genetic marker (17p deletion) who have already undergone at least one prior therapy, and it is being studied for various other blood cancers and conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: First Global Approval. Deeks, ED.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03583424?cond=diffuse-large-b-cell-lymphoma

Venetoclax, Carmustine, Etoposide, Cytarabine, and ... This phase I/II trial studies the side effects and best dose of venetoclax when given together with carmustine, etoposide, cytarabine, and melphalan before stem ...

2. ashpublications.org ashpublications.org/blood/article/134/Supplement_1/5705/425411/A-Phase-I-Trial-of-Venetoclax-in-Combination-with

A Phase I Trial of Venetoclax in Combination with BEAM ... BEAM (BCNU, etoposide, cytarabine, and melphalan) is a commonly used conditioning regimen for NHL but often fails to produce durable ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05863845

Efficacy and Safety of Venetoclax Combined With BEAM ... The results confirmed that Venetoclax has a good prospect in ASCT. Official Title. Efficacy and Safety of Venetoclax Combined With BEAM (Carmustine, Etoposide ...

4. trial.medpath.com trial.medpath.com/clinical-trial/094897fbcc3d16fa/nct03583424-venetoclax-carmustine-etoposide-cytarabine-melphalan-stem-cell-transplant-non-hodgkin

Venetoclax, Carmustine, Etoposide, Cytarabine ... - MedPath This phase I/II trial studies the side effects and best dose of venetoclax when given together with carmustine, etoposide, cytarabine, and melphalan before ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25563428/

High-dose chemotherapy with carmustine, etoposide, ... We present a retrospective analysis of 73 consecutive patients aged over 65 years treated for aggressive or relapsed lymphoma by HDT with carmustine, etoposide, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11513189/

High‐dose chemotherapy followed by autologous stem cell ... BNLI compared conventional chemotherapy (mini‐BEAM (carmustine plus etoposide plus cytarabine plus melphalan)) versus high‐dose chemotherapy (BEAM) followed by ...

7. astctjournal.org astctjournal.org/article/S1083-8791(14)01382-2/pdf

Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) Although outcomes for patients with diffuse large B cell lymphoma (DLBCL) have improved with the addition of rituximab to initial chemotherapy [1,2], a ...