Veliparib + Chemotherapy for Advanced Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP inhibitors, CYP inducers

Disqualifiers: Pregnancy, HIV on ART, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 21 days per cycle

81 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of veliparib, cyclophosphamide, and doxorubicin hydrochloride when given together in treating patients solid tumors or non-Hodgkin lymphoma that has spread to other areas of the body or cannot be removed by surgery. Veliparib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide and doxorubicin hydrochloride, 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. Giving veliparib, cyclophosphamide, and doxorubicin hydrochloride may kill more cancer cells.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications that are strong inhibitors or inducers of certain liver enzymes (CYP 3A4, 2B6, 2C9, or 2C19) at least 7 days before starting the study medication. If you are taking amiodarone, you must stop it 6 months before. Please consult with your doctor to see if your current medications fall into these categories.

What data supports the effectiveness of Veliparib combined with chemotherapy for advanced lymphoma?

The effectiveness of cyclophosphamide and doxorubicin, which are part of the Veliparib combination, is supported by their use in CHOP and R-CHOP regimens, which are standard treatments for aggressive non-Hodgkin's lymphoma. These regimens have shown improved outcomes in treating this type of cancer. ^{1 2 3 4 5}

Is the combination of Veliparib and chemotherapy safe for treating advanced lymphoma?

Doxorubicin, a component of the chemotherapy regimen, can cause heart-related side effects, especially in older patients or those with heart conditions. However, using liposomal forms of doxorubicin has been shown to reduce these heart-related risks, making it a safer option for those at high risk of cardiac events. ^{6 7 8 9 10}

How is the drug Veliparib + Chemotherapy unique for treating advanced lymphoma?

The drug Veliparib combined with chemotherapy is unique because it includes Veliparib, a PARP inhibitor (a type of drug that blocks an enzyme involved in repairing damaged DNA), which is not commonly used in standard lymphoma treatments. This combination aims to enhance the effectiveness of traditional chemotherapy drugs like cyclophosphamide and doxorubicin by potentially making cancer cells more sensitive to treatment. ^{1 3 11 12 13}

Research Team

Mark N Stein

Principal Investigator

Rutgers Cancer Institute of New Jersey

Eligibility Criteria

This trial is for patients with metastatic or unresectable solid tumors or non-Hodgkin lymphoma. Eligible participants must have a life expectancy over 2 months, adequate organ function, and no recent chemotherapy or radiation. They should not be on certain drugs affecting liver enzymes and agree to use contraception. Those with HIV, active infections, heart failure, CNS metastases, or severe allergies to the study drugs are excluded.

Inclusion Criteria

It's been over 4 weeks since my last chemo or radiation (6 if I had BCNU or mitomycin C).

I can take care of myself but might not be able to do heavy physical work.

My heart's pumping ability is normal or above normal.

Exclusion Criteria

I have a history of seizures or currently experience them.

Any other medical, social, or psychological condition that may significantly affect safety and/or compliance

I am not taking medication that strongly affects certain liver enzymes.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive veliparib, cyclophosphamide, and doxorubicin hydrochloride in a dose-escalation study to determine the maximally tolerated dose

21 days per cycle

Multiple visits per cycle for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cyclophosphamide
• Doxorubicin Hydrochloride
• Veliparib

Trial Overview The trial tests the combination of Veliparib with Cyclophosphamide and Doxorubicin Hydrochloride in treating advanced cancers. It aims to find the safest doses while assessing how these drugs affect cancer growth by blocking cell division and spreading.

Participant Groups

Group I: Treatment (veliparib, cyclophosphamide, doxorubicin) Experimental Treatment 5 Interventions

GROUP I: Patients receive veliparib PO every 12 hours on days 1-4 and cyclophosphamide IV over 60 minutes on day 3. GROUP II: Patients receive veliparib PO every 12 hours on days 1-4, cyclophosphamide IV over 60 minutes on day 3, and doxorubicin hydrochloride IV over 15 minutes on day 3. GROUP III: Patients receive veliparib PO every 12 hours on days 1-7, cyclophosphamide IV over 60 minutes on day 1, and doxorubicin hydrochloride IV over 15 minutes on day 1. GROUP IV: Patients receive veliparib PO every 12 hours on days 1-14, cyclophosphamide IV over 60 minutes on day 1, and doxorubicin hydrochloride over 15 minutes on day 1. In all groups, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

The AMOPLACE chemotherapy regimen, which includes additional agents beyond the standard CHOP treatment, achieved a complete response rate of 68% in 60 patients with intermediate to high-grade non-Hodgkin's lymphomas, indicating its potential efficacy.

Despite its effectiveness, AMOPLACE was associated with significant myelosuppression, as 73% of patients experienced low white blood cell counts, and there were two treatment-related deaths, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AMOPLACE treatment of intermediate-grade and high-grade malignant lymphoma: a Cancer and Leukemia Group B study. Parker, BA., Santarelli, M., Green, MR., et al.[2017]

The R-CHOP regimen, which includes rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, is a standard first-line treatment for diffuse large B-cell lymphoma, highlighting its importance in oncology.

Nursing implications of administering R-CHOP are significant, as the combination of these drugs requires careful monitoring for side effects and patient management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nursing Alchemy: Transforming R-CHOP Information Into Essentials. Sakowski, AK., Patel, PR.[2023]

In a study of 50 patients treated with R-CHOP-14 for aggressive B-cell lymphoma, 82% achieved a complete or improved response, indicating high efficacy of this treatment regimen.

Despite its effectiveness, R-CHOP-14 was associated with significant toxicities, including grade 3-4 neutropenia in 32% of patients and peripheral neuropathy in 45%, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with biweekly CHOP plus rituximab chemoimmunotherapy for the treatment of aggressive B-cell non-Hodgkin lymphoma. Aguiar Bujanda, D., Aguiar Morales, J., Bohn Sarmiento, U., et al.[2021]

In a study of 389 young patients with good-prognosis aggressive lymphoma, the high dose of CHOEP-21 did not improve event-free or overall survival compared to the standard CHOEP-21 regimen, indicating no clinical benefit from the increased dosage.

The high CHOEP regimen was associated with significantly higher toxicity, including increased rates of severe leukocytopenia, thrombocytopenia, infections, and therapy-related deaths, suggesting that the risks may outweigh any potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-escalated CHOEP for the treatment of young patients with aggressive non-Hodgkin's lymphoma: II. Results of the randomized high-CHOEP trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). Pfreundschuh, M., Zwick, C., Zeynalova, S., et al.[2020]

The CEOP chemotherapy regimen, which substitutes epirubicin for doxorubicin, demonstrated a high efficacy with a complete remission rate of 64.3% in 186 patients with intermediate- or high-grade non-Hodgkin lymphoma, particularly benefiting elderly patients.

Long-term follow-up showed that 79.8% of patients who achieved complete remission remained disease-free at a median of 86.9 months, indicating that CEOP is not only effective but also well-tolerated, with no deaths from cardiac toxicity reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of patients with intermediate or high-grade non-Hodgkin lymphoma treated with a combination of cyclophosphamide, epirubicin, vincristine, and prednisone. Rossini, F., Terruzzi, E., Perego, D., et al.[2015]

In a study involving 946 patients with non-Hodgkin's lymphoma, the use of nonpeghylated liposomal doxorubicin (NPLD) as a substitute for standard doxorubicin resulted in a high complete remission rate of 72.6%, demonstrating its efficacy in treating this population.

The incidence of major cardiotoxic events was relatively low at 5%, indicating that NPLD significantly reduces the risk of heart-related complications, making it a safer option for elderly patients and those with pre-existing cardiac conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonpeghylated liposomal doxorubicin combination regimen (R-COMP) for the treatment of lymphoma patients with advanced age or cardiac comorbidity. Rigacci, L., Annibali, O., Kovalchuk, S., et al.[2020]

In a phase II study involving 47 patients with various types of sarcoma, pegylated-liposomal doxorubicin (Doxil) demonstrated activity, with 3 patients achieving complete or partial responses and 15 experiencing clinical benefits despite being previously treated or unresponsive to chemotherapy.

The treatment was generally well tolerated, with mild toxicities primarily related to mucositis and hand-foot syndrome, and no significant cardiac toxicity observed, indicating a favorable safety profile for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of pegylated-liposomal doxorubicin (Doxil) in sarcoma. Skubitz, KM.[2022]

In a study of 30 patients with refractory or relapsing non-Hodgkin's lymphoma, the DVIP treatment led to a 33% complete response rate and a 30% partial response rate, with responses lasting from 2.5 to over 24 months.

While DVIP treatment caused significant myelosuppression, it was considered safe as there were no drug-related deaths, indicating it is an effective salvage therapy for aggressive forms of NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage therapy for non-Hodgkin's lymphoma with a combination of dexamethasone, etoposide, ifosfamide, and cisplatin. Haim, N., Rosenblatt, E., Wollner, M., et al.[2019]

The hyper-CVAD regimen, which includes cyclophosphamide, vincristine, doxorubicin, and dexamethasone, has shown significant effectiveness in treating adult lymphocytic leukemia and other blood cancers, such as Burkitt's disease and multiple myeloma.

Clinical trials conducted at the University of Texas M. D. Anderson Cancer Center have provided strong evidence for the efficacy of hyper-CVAD, leading to ongoing discussions about strategies to enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The hyper-CVAD regimen in adult acute lymphocytic leukemia. Garcia-Manero, G., Kantarjian, HM.[2019]

In a study of 195 patients with relapsed/refractory aggressive B-cell lymphomas, the overall response rate to second-line platinum-based immunochemotherapy was 44%, with a median progression-free survival (PFS) of 3 months and overall survival (OS) of 8 months.

Patients who experienced early treatment failure (relapse within 12 months of first-line therapy) had significantly worse outcomes, with a median PFS of only 2.8 months and OS of 6 months, suggesting a need for alternative treatment strategies in this high-risk group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes in patients with aggressive B-cell non-Hodgkin lymphoma after intensive frontline treatment failure. Ayers, EC., Li, S., Medeiros, LJ., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

AMOPLACE treatment of intermediate-grade and high-grade malignant lymphoma: a Cancer and Leukemia Group B study. [2017]

2. United States pubmed.ncbi.nlm.nih.gov

Infusional CHOP chemotherapy (CVAD) with or without chemosensitizers offers no advantage over standard CHOP therapy in the treatment of lymphoma: a Southwest Oncology Group Study. [2017]

3. United States pubmed.ncbi.nlm.nih.gov

Nursing Alchemy: Transforming R-CHOP Information Into Essentials. [2023]

4. Italy pubmed.ncbi.nlm.nih.gov

Clinical experience with biweekly CHOP plus rituximab chemoimmunotherapy for the treatment of aggressive B-cell non-Hodgkin lymphoma. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Dose-escalated CHOEP for the treatment of young patients with aggressive non-Hodgkin's lymphoma: II. Results of the randomized high-CHOEP trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Long-term follow-up of patients with intermediate or high-grade non-Hodgkin lymphoma treated with a combination of cyclophosphamide, epirubicin, vincristine, and prednisone. [2015]

7. England pubmed.ncbi.nlm.nih.gov

Nonpeghylated liposomal doxorubicin combination regimen (R-COMP) for the treatment of lymphoma patients with advanced age or cardiac comorbidity. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Chemotherapy with a Pegylated Liposomal Doxorubicin-Containing Regimen in Newly Diagnosed Hodgkin Lymphoma Patients. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Phase II trial of pegylated-liposomal doxorubicin (Doxil) in sarcoma. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Comparison of CHOP-B vs CEOP-B in 'poor prognosis' non-Hodgkin's lymphomas. A randomized trial. [2019]

11. Germany pubmed.ncbi.nlm.nih.gov

Salvage therapy for non-Hodgkin's lymphoma with a combination of dexamethasone, etoposide, ifosfamide, and cisplatin. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

The hyper-CVAD regimen in adult acute lymphocytic leukemia. [2019]

13. United States pubmed.ncbi.nlm.nih.gov

Outcomes in patients with aggressive B-cell non-Hodgkin lymphoma after intensive frontline treatment failure. [2020]