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Bruton's Tyrosine Kinase (BTK) Inhibitor

Ibrutinib + Stem Cell Transplant for Lymphoma

Phase 3

Waitlist Available

Led By Charalambos B Andreadis

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients should not require concurrent therapeutic doses of steroids (> 20 mg of prednisone/day or equivalent) unless they need them for the indications; steroids should be discontinued for 14 days before starting protocol treatment

Use of HIV protease inhibitors as part of the anti-HIV regimen OR as a pharmacologic booster is not allowed

Timeline

Screening 3 weeks

Treatment Varies

Follow Up the time between randomization and death from any cause, assessed up to 5 years (60 months)

Awards & highlights

Pivotal Trial

Summary

This trial is studying whether adding ibrutinib to chemotherapy before and after stem cell transplant helps the transplant work better in patients with relapsed or refractory diffuse large B-cell lymphoma.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Ibrutinib may cause side effects such as diarrhea, bleeding problems, high blood pressure, fatigue, muscle and bone pain. It might also increase the risk of infections due to its effect on cancer cells' growth pathways.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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

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I can take care of myself and am up and about more than half of my waking hours.

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My heart functions well during normal activities and I'm over 60 with an LVEF of 40% or more.

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My condition worsened or didn't respond to previous chemotherapy that included anthracyclines.

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I am using or willing to use effective birth control during and for one month after the study.

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I don't use strong medication that affects liver enzyme levels regularly.

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I am not taking Zidovudine.

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I have a bleeding disorder.

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I have hepatitis B or C but my PCR test for the virus is negative.

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I am not taking HIV medication that includes a booster like cobicistat.

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I do not have multi-drug resistant HIV.

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My tests show early signs of a bone marrow disorder before starting treatment.

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I have not taken warfarin or similar drugs in the last 28 days.

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I have significant liver problems (Child-Pugh class B or C).

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My lung function, measured by FEV1, is at least 40% of the expected value.

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My lymphoma is confirmed as non-GCB diffuse large B-cell type.

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My kidney function, measured by creatinine levels or clearance, is within the required range.

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I am 18 years old or older.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ the time between randomization and death from any cause, assessed up to 5 years (60 months)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~the time between randomization and death from any cause, assessed up to 5 years (60 months)

This trial's timeline: 3 weeks for screening, Varies for treatment, and the time between randomization and death from any cause, assessed up to 5 years (60 months) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

24-month progression-free survival (PFS), defined as the proportion of patients who are alive and progression-free 2 years from randomization

Secondary study objectives

Incidence of hematologic toxicity of ibrutinib therapy

Incidence of secondary malignancies

Overall survival (OS)

+4 more

Other study objectives

Body tissue

BCR pathway mutations

Fludeoxyglucose positron emission tomography (FDG-PET) imaging results

+3 more

Side effects data

From 2022 Phase 3 trial • 665 Patients • NCT00567567

84%

58300-Neutrophil count decreased

70%

65800-Platelet count decreased

20%

43100-Hypokalemia

18%

44800-Infections and infestations - Other specify

18%

33300-Febrile neutropenia

17%

88500-White blood cell decreased

13%

13200-Anemia

55600-Mucositis oral

42700-Hypocalcemia

13500-Anorexia

11600-Alanine aminotransferase increased

41400-Hyperglycemia

15000-Aspartate aminotransferase increased

43300-Hyponatremia

73700-Sepsis

53700-Lymphocyte count decreased

25700-Diarrhea

65900-Pleural effusion

57600-Nausea

37500-GGT increased

41600-Hyperkalemia

10300-Abdominal pain

20500-Catheter related infection

59700-Oral pain

38900-Hearing impaired

43900-Hypoxia

17200-Blood and lymphatic system disorders - Other specify

14900-Ascites

75700-Small intestinal obstruction

87900-Vomiting

43600-Hypotension

45800-INR increased

34000-Fibrinogen decreased

23000-Confusion

42600-Hypoalbuminemia

69700-Rash maculo-papular

71500-Respiratory failure

73900-Serum amylase increased

26600-Duodenal obstruction

66300-Pneumonitis

58000-Neoplasms benign malignant and unspecified (incl cysts and polyps) - Other specify

56600-Myelitis

75600-Small intestinal mucositis

66800-Postoperative hemorrhage

43500-Hypophosphatemia

37300-Generalized muscle weakness

81200-Treatment related secondary malignancy

31200-Esophagitis

83100-Urinary tract infection

24100-Creatinine increased

11100-Acute kidney injury

62600-Pelvic pain

65300-Pharyngolaryngeal pain

31900-Eye disorders - Other specify

10900-Activated partial thromboplastin time prolonged

11800-Alkaline phosphatase increased

42500-Hyperuricemia

17400-Blood bilirubin increased

63100-Pericardial effusion

72700-Right ventricular dysfunction

37200-General disorders and administration site conditions - Other specify

40000-Hepatic failure

88200-Weight gain

41300-Hypercalcemia

54900-Metabolism and nutrition disorders - Other specify

71000-Renal and urinary disorders - Other specify

69000-Pulmonary hypertension

20100-Cardiac disorders - Other specify

22100-Colitis

44200-Ileal obstruction

81900-Typhlitis

33900-Fever

35500-Gallbladder pain

40600-Hepatobiliary disorders - Other specify

66500-Portal hypertension

12000-Allergic reaction

13100-Anaphylaxis

44700-Immune system disorders - Other specify

13400-Anorectal infection

25600-Device related infection

29500-Enterocolitis infectious

53100-Lung infection

62500-Pelvic infection

75200-Skin infection

82300-Upper respiratory infection

14500-Arterial injury

15300-Ataxia

38800-Headache

63900-Peripheral motor neuropathy

11300-Adult respiratory distress syndrome

29700-Epistaxis

78100-Stridor

68400-Pruritus

51700-Left ventricular systolic dysfunction

27800-Dyspnea

58100-Nervous system disorders - Other specify

29000-Encephalopathy

42100-Hypertension

24700-Dehydration

43200-Hypomagnesemia

31800-Extrapyramidal disorder

52600-Lipase increased

10700-Acidosis

100%

80%

60%

40%

20%

Study treatment Arm

Tandem HST (CEM), Randomly Assigned

Single HST (CEM)

Not Assigned

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Arm I (ibrutinib, chemotherapy, autoHCT)Experimental Treatment10 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 Group10 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Autologous Hematopoietic Stem Cell Transplantation

2017

Completed Phase 3

~2090

Cyclophosphamide

2010

Completed Phase 4

~2310