Ibrutinib + FCR for Chronic Lymphocytic Leukemia

(iFCR Trial)

Not currently recruiting at 8 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of medications, including ibrutinib, to determine its effectiveness in treating Chronic Lymphocytic Leukemia (CLL). Ibrutinib, a type of targeted therapy, will be used alongside standard drugs fludarabine, cyclophosphamide, and rituximab. The goal is to assess whether this combination is more effective than the standard treatment alone. The trial seeks participants diagnosed with CLL who experience symptoms like severe fatigue or night sweats and have not received previous treatment for CLL. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those on certain immunosuppressants, warfarin, or strong CYP3A inhibitors or inducers. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining ibrutinib with fludarabine, cyclophosphamide, and rituximab (FCR) is generally safe. In earlier studies, patients who took ibrutinib and rituximab experienced fewer serious side effects than those who only received the standard FCR treatment.

Early results suggest that ibrutinib with FCR is usually well-tolerated. Most side effects are manageable and similar to those from standard treatments. Common side effects include mild nausea, tiredness, and low blood cell counts, which are typical in cancer treatments and can often be managed with additional care.

These findings are promising for those considering joining the trial, as the treatments have been tested for safety and many patients have tolerated them well. However, discussing personal health and potential risks with a healthcare provider before participating is important.12345

Why do researchers think this study treatment might be promising for CLL?

Researchers are excited about the combination treatment of Ibrutinib with FCR (Fludarabine, Cyclophosphamide, and Rituximab) for Chronic Lymphocytic Leukemia because it offers a new mechanism of action. Ibrutinib works by inhibiting Bruton's tyrosine kinase, an enzyme crucial for the survival and proliferation of leukemia cells, which is different from traditional chemotherapy approaches that broadly target rapidly dividing cells. This targeted approach has the potential to improve efficacy and reduce side effects compared to conventional treatments like chemotherapy alone. Additionally, the oral administration of Ibrutinib provides greater convenience for patients compared to intravenous therapies. Researchers are hopeful that this combination will lead to better outcomes for patients.

What evidence suggests that ibrutinib in combination with FCR could be an effective treatment for Chronic Lymphocytic Leukemia?

This trial will evaluate the combination of Ibrutinib with FCR (Fludarabine, Cyclophosphamide, and Rituximab) for treating Chronic Lymphocytic Leukemia (CLL). Studies have shown that combining Ibrutinib with Rituximab helps people with CLL live longer without disease progression compared to traditional treatments like FCR. Research indicates that this combination is effective for patients, regardless of specific gene mutations. Additionally, studies on combining Ibrutinib with FCR show promise in treating CLL. This treatment stops cancer cells from growing and surviving, which may explain its effectiveness. Overall, evidence supports optimism for Ibrutinib's role in improving CLL treatment.34678

Who Is on the Research Team?

Matthew S. Davids, MD, MMSc - Dana ...

Matthew S. Davids

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

Adults aged 18-65 with confirmed chronic lymphocytic leukemia or small lymphocytic lymphoma who need treatment based on specific criteria like worsening anemia, significant weight loss, fatigue, fevers without infection, and night sweats. They should not have had previous CLL therapy and must be able to perform daily activities (ECOG ≤1). Adequate blood counts and liver/renal function are required. Participants must use effective contraception.

Inclusion Criteria

I am too tired to work or do my usual activities.
Bilirubin ≤ 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
My liver and kidney functions are within normal ranges.
See 22 more

Exclusion Criteria

I have not received any live vaccines in the last 4 weeks.
I am not on warfarin or vitamin K antagonists for blood thinning.
I am on preventive antibiotics with no active infection and my medication is not prohibited.
See 23 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ibrutinib in combination with fludarabine, cyclophosphamide, and rituximab (FCR) for up to 6 cycles

24 weeks
6 cycles (28 days each)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including bone marrow biopsies and PET CT scans

2 months
Bone marrow biopsy and PET CT scan

Ibrutinib Maintenance

Participants continue with ibrutinib maintenance therapy to assess long-term response

24 months

Long-term Follow-up

Participants are monitored for progression-free survival and overall survival

63.24 months (median follow-up)

What Are the Treatments Tested in This Trial?

Interventions

  • Cyclophosphamide
  • Fludarabine
  • Ibrutinib
  • Rituximab
Trial Overview The trial is testing a new drug combination for treating Chronic Lymphocytic Leukemia (CLL). It involves adding the drug Ibrutinib to the standard FCR regimen (Fludarabine, Cyclophosphamide, Rituximab) to see if it improves outcomes in younger patients who haven't been treated before.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: IbrutinibExperimental Treatment4 Interventions

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

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Approved in United States as Cytoxan for:
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Approved in European Union as Endoxan for:
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Approved in Canada as Neosar for:
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Approved in Japan as Endoxan for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials
1,128
Recruited
382,000+

Pharmacyclics LLC.

Industry Sponsor

Trials
114
Recruited
13,800+

Dr. Maky Zanganeh

Pharmacyclics LLC.

Chief Executive Officer

Degree from Louis Pasteur University in Strasbourg, France; MBA from Schiller International University in France

Dr. Ellie Im

Pharmacyclics LLC.

Chief Medical Officer

MD from an unspecified institution

The Leukemia and Lymphoma Society

Collaborator

Trials
87
Recruited
26,200+

Blood Cancer Research Partnership

Collaborator

Trials
5
Recruited
230+

Published Research Related to This Trial

In the phase 3 HELIOS trial involving 578 patients with previously treated chronic lymphocytic leukemia (CLL), the combination of ibrutinib and bendamustine-rituximab (BR) significantly improved progression-free survival (PFS) compared to placebo+BR, with a median PFS not reached for ibrutinib+BR versus 14.3 months for placebo+BR.
The treatment with ibrutinib+BR also resulted in a higher rate of minimal residual disease (MRD)-negative responses (26.3% vs. 6.2% for placebo+BR), indicating a deeper response to therapy, while the safety profile remained consistent with earlier reports.
Updated results from the phase 3 HELIOS study of ibrutinib, bendamustine, and rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma.Fraser, G., Cramer, P., Demirkan, F., et al.[2023]
In a phase 1b study involving patients with relapsed/refractory chronic lymphocytic leukemia, the combination of ibrutinib with bendamustine and rituximab (BR) showed a high overall response rate of 93.3%, with significant improvements in complete responses over time.
The study demonstrated that ibrutinib can enhance the efficacy of chemoimmunotherapy without adding prolonged hematologic toxicity, suggesting a promising treatment strategy for patients with this type of leukemia.
The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia.Brown, JR., Barrientos, JC., Barr, PM., et al.[2021]
In the HELIOS trial involving 578 subjects, the combination of bendamustine/rituximab and ibrutinib (BR-I) resulted in significantly higher systemic exposure to rituximab compared to bendamustine/rituximab with placebo (BR), particularly in the initial treatment cycles.
The study found no significant safety differences between the BR-I and BR groups, suggesting that the enhanced efficacy of BR-I may be achieved without compromising patient safety.
Systemic Exposure of Rituximab Increased by Ibrutinib: Pharmacokinetic Results and Modeling Based on the HELIOS Trial.Lavezzi, SM., de Jong, J., Neyens, M., et al.[2021]

Citations

1.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/35427411/
updated results of the E1912 trial - PubMed - NIHHerein, we present the long-term follow-up of the randomized E1912 trial comparing the long-term efficacy of ibrutinib-rituximab (IR) therapy to ...
Long-term outcomes for ibrutinib–rituximab and ...After a median follow-up of 6 years, IR led to superior PFS relative to FCR in patients with both IGHV muted and IGHV unmutated CLL.
Ibrutinib and rituximab versus fludarabine ...The National Cancer Research Institute (NCRI) FLAIR trial compared efficacy and toxicity of ibrutinib and rituximab with fludarabine, cyclophosphamide, and ...
NCT02251548 | A Phase II Study of Ibrutinib Plus FCR in ...This research study is evaluating a new drug called ibrutinib in combination with the standard drugs fludarabine, cyclophosphamide, and rituximab (FCR)
Ibrutinib–Rituximab or Chemoimmunotherapy for Chronic ...The ibrutinib–rituximab regimen resulted in progression-free survival and overall survival that were superior to those with a standard chemoimmunotherapy ...
6.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/37142374/
Ibrutinib and rituximab versus fludarabine ...We aimed to assess whether ibrutinib and rituximab is superior to fludarabine, cyclophosphamide, and rituximab in terms of progression-free survival.
Study Details | NCT02048813 | Ibrutinib and Rituximab ...This phase III trial studies ibrutinib and rituximab to see how well they work compared to fludarabine phosphate, cyclophosphamide, and rituximab in treating ...
Ibrutinib plus fludarabine, cyclophosphamide, and ...Previously, high rates of undetectable minimal residual disease were observed after ibrutinib plus fludarabine, cyclophosphamide, and rituximab ...
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