Ibrutinib + Stem Cell Transplant for Lymphoma

Recruiting at 307 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Strong CYP3A inhibitors, Strong CYP3A inducers, HIV protease inhibitors, Zidovudine

Disqualifiers: Active CNS involvement, Hepatic impairment, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

92 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized phase III trial studies ibrutinib to see how well it works compared to placebo when given before and after stem cell transplant in treating patients with diffuse large B-cell lymphoma that has returned after a period of improvement (relapsed) or does not respond to treatment (refractory). Before transplant, stem cells are taken from patients and stored. Patients then receive high doses of chemotherapy to kill cancer cells and make room for healthy cells. After treatment, the stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Ibrutinib is a drug that may stop the growth of cancer cells by blocking a protein that is needed for cell growth. It is not yet known whether adding ibrutinib to chemotherapy before and after stem cell transplant may help the transplant work better in patients with relapsed or refractory diffuse large B-cell lymphoma.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you should not require chronic use of strong CYP3A inhibitors or inducers, and you should not need therapeutic doses of steroids unless necessary. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Ibrutinib in treating lymphoma?

Ibrutinib has been shown to be effective in treating certain types of blood cancers, like chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), by improving survival rates and response to treatment. It works by blocking signals that help cancer cells grow, and has been approved for use in these conditions due to its positive results in clinical trials. ^{1 2 3 4 5}

Is the combination of Ibrutinib and Stem Cell Transplant generally safe for humans?

Ibrutinib (Imbruvica) has been used in various treatments and is generally considered to have an acceptable safety profile, but it can cause side effects like bleeding, infections, and heart issues. The most common side effects include muscle pain, fever, pneumonia, stomach pain, mouth sores, diarrhea, and headache. While these findings are from studies on different conditions, they provide some insight into the safety of Ibrutinib in humans. ^{1 2 4 5 6}

How is the drug Ibrutinib unique for treating lymphoma?

Ibrutinib is unique because it is an oral medication that specifically targets Bruton's tyrosine kinase, a key player in B-cell receptor signaling, which helps reduce the growth of cancerous B cells. This mechanism makes it a novel option compared to traditional chemotherapy, and it is particularly effective in patients with certain genetic mutations like del(17p) or TP53 mutation. ^{1 2 4 5 7}

Research Team

Charalambos B Andreadis

Principal Investigator

Alliance for Clinical Trials in Oncology

Eligibility Criteria

Adults with relapsed or refractory diffuse large B-cell lymphoma eligible for stem cell transplant can join. They must have responded at least partially to prior chemotherapy, be in good physical condition, and not have severe heart, lung, liver issues or active infections like hepatitis B/C or HIV with complications. Pregnant/nursing individuals and those on certain drugs are excluded.

Inclusion Criteria

I am not on high doses of steroids, or can stop them 14 days before treatment.

I am not using HIV protease inhibitors for my HIV treatment.

Patients cannot have:

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Regimen

Patients receive either the BEAMi or CBVi regimen, including ibrutinib or placebo, followed by high-dose chemotherapy to prepare for stem cell transplant

1 week

Daily visits for chemotherapy administration

Transplant

Patients undergo autologous hematopoietic progenitor cell or bone marrow transplant

1 day

Inpatient procedure

Continuation Regimen

Patients receive ibrutinib or placebo for 12 cycles, starting 30-60 days post-transplant, in the absence of disease progression or unacceptable toxicity

12 months

Monthly visits for treatment cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 60 months

Every 6 months

Treatment Details

Interventions

• Autologous Bone Marrow Transplantation
• Autologous Hematopoietic Stem Cell Transplantation
• Ibrutinib

Trial Overview The trial is testing if adding the drug Ibrutinib to standard high-dose chemotherapy before and after a stem cell transplant can improve outcomes in patients with difficult-to-treat lymphoma compared to a placebo.

Participant Groups

Group I: Arm I (ibrutinib, chemotherapy, autoHCT) Experimental Treatment 10 Interventions

CONDITIONING REGIMEN: Investigators may choose to use either the BEAMi or CBVi regimen. BEAMi: Patients receive ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, carmustine IV over 2 hours on day -6, etoposide IV BID over 1-2 hours and cytarabine IV BID over 1-2 hours on days -5 to -2, and melphalan IV over 20-30 minutes on day -1. CBVi: Patients receive ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, carmustine IV over 2 hours on day -6, etoposide IV over 4 hours on day -4, and cyclophosphamide IV on day -2. TRANSPLANT: In both arms, patients undergo autologous hematopoietic progenitor cell or bone marrow transplant on day 0. CONTINUATION REGIMEN: Beginning 30-60 days after transplant, patients receive ibrutinib PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm II (placebo, chemotherapy, autoHCT) Placebo Group 10 Interventions

CONDITIONING REGIMEN: Patients receive placebo PO on days -6 to -1 and receive 1 of the 2 conditioning regimens as in Arm I. TRANSPLANT: Patients undergo autologous hematopoietic progenitor cell or bone marrow transplant on day 0. CONTINUATION REGIMEN: Beginning 30-60 days after transplant, patients receive placebo PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may crossover Arm I.

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

Approved in European Union as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in United States as Imbruvica for:

• Chronic lymphocytic leukemia/small lymphocytic lymphoma
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in Canada as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma

Approved in Japan as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Ibrutinib is an effective treatment for chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL), showing better outcomes than traditional therapies like chlorambucil and ofatumumab in phase III trials involving elderly and previously-treated patients.

The drug has a good safety profile, although it can cause some adverse effects like bleeding and atrial fibrillation; it is recommended in treatment guidelines for patients with high-risk disease, including those with specific genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: A Review in Chronic Lymphocytic Leukaemia. Deeks, ED.[2021]

Ibrutinib is a first-in-class oral Bruton's tyrosine kinase inhibitor that effectively blocks B-cell signaling, leading to reduced proliferation and increased cell death in B cell malignancies, including chronic lymphocytic leukaemia (CLL) and mantle cell lymphoma (MCL).

It has received FDA approval for treating MCL in previously treated patients based on phase Ib/II study results and is currently undergoing further phase III trials for CLL, diffuse large B cell lymphoma (DLBCL), and other B cell cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: first global approval. Cameron, F., Sanford, M.[2022]

Ibrutinib is a targeted therapy specifically designed for treating chronic lymphocytic leukemia (CLL), which is a type of cancer that affects the blood and bone marrow.

This novel treatment works by inhibiting Bruton's tyrosine kinase (BTK), a key enzyme that helps cancer cells survive and proliferate, leading to improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. Parmar, S., Patel, K., Pinilla-Ibarz, J.[2021]

Ibrutinib is an effective oral treatment for patients with relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukaemia (CLL), showing a 68% overall response rate in MCL and significant improvements in progression-free survival and overall survival in CLL patients, including those with specific genetic mutations.

The drug has a good safety profile, with less than 10% of patients discontinuing treatment due to adverse effects, making it a promising option for patients with various B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ibrutinib: A new drug of B-cell malignancies]. Thieblemont, C.[2021]

Ibrutinib (Imbruvica) is now approved for treating graft-versus-host disease in pediatric patients aged one year and older who have not responded to other systemic therapies, highlighting its efficacy in a challenging patient population.

The treatment carries significant risks, including severe side effects like hemorrhage, infections, and cardiac issues, necessitating careful monitoring and education for patients and caregivers about these potential adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Receives New Indication for Pediatric Graft-Versus-Host Disease. Aschenbrenner, DS.[2023]

Ibrutinib is a powerful oral medication that effectively treats relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukaemia (CLL), showing high response rates and significantly improving survival outcomes, especially in patients with poor prognostic factors like chromosome 17 deletion (del 17p).

The drug has a good safety profile, with less than 10% of patients discontinuing treatment due to side effects, making it a promising option for patients with these types of blood cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: a review of its use in patients with mantle cell lymphoma or chronic lymphocytic leukaemia. Kim, ES., Dhillon, S.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Ibrutinib: A Review in Chronic Lymphocytic Leukaemia. [2021]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Ibrutinib: first global approval. [2022]

3. England pubmed.ncbi.nlm.nih.gov

The iR2 regimen (ibrutinib plus lenalidomide and rituximab) for relapsed/refractory DLBCL: A multicentre, non-randomised, open-label phase 2 study. [2023]

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

Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. [2021]

5. France pubmed.ncbi.nlm.nih.gov

[Ibrutinib: A new drug of B-cell malignancies]. [2021]

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

Drug Receives New Indication for Pediatric Graft-Versus-Host Disease. [2023]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Ibrutinib: a review of its use in patients with mantle cell lymphoma or chronic lymphocytic leukaemia. [2022]