IPI-145 + FCR for Chronic Lymphocytic Leukemia

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Dana-Farber Cancer Institute

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

Compensation: Varies

Number of Visits: 9

32 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is evaluating a new drug called IPI-145 in combination with the standard drugs fludarabine, cyclophosphamide, and rituximab (FCR), as a possible treatment for chronic lymphocytic leukemia (CLL).

Will I have to stop taking my current medications?

The trial requires that you stop taking foods or medications that strongly affect CYP3A enzymes (which help process drugs in the body) at least one week before starting the study and throughout its duration.

What data supports the effectiveness of the drug combination IPI-145 + FCR for Chronic Lymphocytic Leukemia?

Research shows that the combination of fludarabine, cyclophosphamide, and rituximab (FCR) is highly effective for treating chronic lymphocytic leukemia, with a 95% overall response rate and 72% complete remission in patients. This suggests that adding IPI-145 to this regimen could potentially enhance its effectiveness. ^{1 2 3 4 5}

Is the combination of IPI-145, fludarabine, cyclophosphamide, and rituximab safe for humans?

The combination of fludarabine, cyclophosphamide, and rituximab (FCR) has been shown to cause significant blood-related side effects, such as myelosuppression (a decrease in bone marrow activity leading to fewer blood cells), which can lead to infections and other complications. This treatment is generally less well tolerated in older patients, especially those over 70 years old. ^{6 7 8 9 10}

What makes the IPI-145 + FCR drug unique for treating chronic lymphocytic leukemia?

The IPI-145 + FCR drug is unique because it combines a novel agent, IPI-145, with the established FCR regimen (fludarabine, cyclophosphamide, and rituximab), potentially enhancing the treatment's effectiveness while aiming to reduce the high toxicity levels associated with traditional FCR therapy. ^{1 3 5 11 12}

Research Team

Matthew S. Davids

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for younger patients aged 18-65 with confirmed chronic lymphocytic leukemia (CLL) who need treatment but haven't had any yet. They should be relatively healthy, not pregnant, and free from other cancers unless it's low-risk or treated within the past 5 years. People with poor liver or kidney function, heart issues, certain infections or diseases like HIV are excluded.

Inclusion Criteria

I have been diagnosed with CLL and need treatment.

I have not received any treatment for chronic lymphocytic leukemia.

I can carry out all my self-care but cannot do heavy physical work.

Exclusion Criteria

My cancer has spread to my brain or spinal cord.

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

I've been cancer-free for 5 years, except for certain low-risk types.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Dose escalation to find the highest safe dose of IPI-145 in combination with FCR

35 days for Cycle 1, 28 days per subsequent cycle

Weekly visits during Cycle 1, Day 1 visits for subsequent cycles

Phase II Treatment

Treatment with IPI-145 at the Recommended Phase II Dose (RP2D) in combination with FCR

Up to 6 cycles

Day 1 visits for each cycle

Maintenance

IPI-145 maintenance therapy for up to 2 years after completing chemotherapy

Up to 2 years

Every other cycle Day 1 during maintenance

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 6 months

Treatment Details

Interventions

• Cyclophosphamide
• Fludarabine
• IPI-145
• Rituximab

Trial Overview The study tests a new drug called IPI-145 combined with standard CLL treatments: fludarabine, cyclophosphamide, and rituximab (FCR). It aims to see if adding IPI-145 improves outcomes for those who have never been treated for CLL before.

Participant Groups

Group I: IPI-145 Experimental Treatment 4 Interventions

Phase I-Dose escalation will occur using a standard 3-3 dose escalation beginning in dose level 1 with dose cohorts and escalation. * Each treatment cycle lasts 28 days (except cycle 1, which is 35 days) during which time IPI-145 will be taken twice daily. The study begins with 1 week of IPI-145 monotherapy. * Fludarabine, cyclophosphamide, rituximab (iFCR) - FCR will subsequently be introduced after 1 week and administered at standard dosing for up to 6 cycles, with dose reductions permitted. IPI-145 will be continued through the course of chemotherapy and for up to 2 years maintenance after completing chemotherapy Phase II - 20 additional patients treated with IPI-145 at the Recommended Phase II Dose (RP2D) + fludarabine, cyclophosphamide, rituximab (FCR) with standard dosing.

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?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Verastem, Inc.

Industry Sponsor

Trials

42

Recruited

2,800+

Secura Bio, Inc.

Industry Sponsor

Trials

9

Recruited

200+

Findings from Research

The combination therapy of fludarabine, cyclophosphamide, and rituximab (FCR) achieved a high complete remission (CR) rate of 70% in 224 previously untreated patients with chronic lymphocytic leukemia (CLL), indicating its efficacy as an initial treatment.

Despite the high response rate, the treatment was associated with significant side effects, including grade 3 to 4 neutropenia in 52% of treatment courses and a notable incidence of infections, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. Keating, MJ., O'Brien, S., Albitar, M., et al.[2021]

In a study involving 561 patients with chronic lymphocytic leukaemia, the standard treatment of fludarabine, cyclophosphamide, and rituximab showed a longer median progression-free survival of 55.2 months compared to 41.7 months for the bendamustine and rituximab combination, indicating that the standard therapy is more effective.

However, the bendamustine and rituximab combination was associated with significantly fewer severe side effects, such as neutropenia and infections, making it a potentially safer alternative for patients, especially those over 65 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial. Eichhorst, B., Fink, AM., Bahlo, J., et al.[2022]

References

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

Chemoimmunotherapy with low-dose fludarabine and cyclophosphamide and high dose rituximab in previously untreated patients with chronic lymphocytic leukemia. [2015]

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

Phase III trial of fludarabine plus cyclophosphamide compared with fludarabine for patients with previously untreated chronic lymphocytic leukemia: US Intergroup Trial E2997. [2013]

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

Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia. [2023]

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

Cost-Effectiveness Analysis of Rituximab for Chronic Lymphocytic Leukemia Using a Semi-Markovian Model Approach in R. [2023]

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

Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. [2021]

6. India pubmed.ncbi.nlm.nih.gov

Bendamustine-Rituximab in Young CLL: Relevance in the Era of Small Molecule Inhibitors. [2023]

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

Fludarabine plus cyclophosphamide and rituximab in Waldenstrom macroglobulinemia: an effective but myelosuppressive regimen to be offered to patients with advanced disease. [2022]

8. England pubmed.ncbi.nlm.nih.gov

First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial. [2022]

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

How applicable is fludarabine, cyclophosphamide and rituximab to the elderly? [2019]

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

Myelosuppression after frontline fludarabine, cyclophosphamide, and rituximab in patients with chronic lymphocytic leukemia: analysis of persistent and new-onset cytopenia. [2021]

11. China pubmed.ncbi.nlm.nih.gov

[Clinical analysis of fludarabine and cyclophosphamide combined with rituximab in the first-line treatment of 43 cases of chronic lymphoblastic leukemia]. [2021]

12. China pubmed.ncbi.nlm.nih.gov

[Treatment of chronic lymphocytic leukemia with regimen of fludarabine, cyclophosphamide and rituximab]. [2016]