A Study to Evaluate Efficacy & Safety of Obinutuzumab, Ibrutinib, and Venetoclax in Richter's Syndrome;

Plain-language summary

This study evaluates the effectiveness and safety of combining the drugs Obinutuzumab, Ibrutinib, and Venetoclax in people with Richter's syndrome, a transformation into diffuse large B-cell lymphoma (DLBCL). Patients aged 18 and over with a histologically confirmed diagnosis and at least one measurable site of disease could take part. It was carried out as a Phase 2 study and has been completed.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

Phase 2

Status

Completed

Sponsor

Bnai Zion Medical Center

Intervention

Obinutuzumab with Ibrutinib and Venetoclax

Start date

8/8/2021

Estimated completion

12/4/2024

Countries

Israel

Related genes

Locations

• Haifa, Israel
• Jerusalem, Israel
• Tel Aviv, Israel
• Tel Litwinsky, Israel

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

Inclusion Criteria:

1. Subject must be 18 years of age or older.
2. Patients with histopathological confirmation of Richter's transformation into diffuse large B-cell lymphoma (DLBCL).
3. Subjects must have at least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma. The site of disease must be greater than 1.5 cm in the long axis regardless of short axis measurement or greater than 1.0 cm in the short axis regardless of long axis measurement, and clearly measurable in 2 perpendicular dimensions.
4. Eastern Cooperative Oncology Group (ECOG) status 0 to 2; ECOG 3 is only permitted if related to RS.
5. Adequate renal function, as indicated by an estimated creatinine clearance higher than 30 ml/min, adequate platelet count \> 25 x 109/L, adequate liver function as indicated by total bilirubin \< x 2 and Alanine transaminase (ALT) \< x 2.5 of the institutional upper normal levels, unless directly attributable to the RS or to Gilbert's Syndrome.
6. Negative serological testing for hepatitis B (anti-hepatitis Bc negative, patients positive for anti-hepatitis Bc may be included if Polymerase chain reaction (PCR) for HBV DNA is negative) and negative HIV test performed within 6 weeks prior to enrollment.
7. Ability and agreement to provide written informed consent and to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

1. Diagnosed or treated for malignancy other than DLBCL-RS or CLL/Small Lymphocytic Lymphoma (SLL) , except:

   1. Malignancy treated with curative intent and with no known active disease present at enrollment.
   2. Adequately treated non-melanoma skin cancer or lentigo maligna melanoma without evidence of disease.
   3. Adequately treated carcinoma in situ without evidence of disease.
2. Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of enrollment, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification.
3. Requires anticoagulation with coumadin or equivalent vitamin K antagonists (e.g., phenprocoumon).
4. Requirement of therapy with strong CYP3A4 and CYP3A5 inhibitors/inducers.
5. Documented resistance to Ibrutinib and/or Venetoclax.
6. Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment; further pregnancy testing will be performed regularly).
7. Fertile men or women of childbearing potential unless:

   1. surgically sterile or ≥ 2 years after the onset of menopause
   2. Willing to use two methods of reliable contraception including one highly effective contraceptive method (Pearl Index \<1) and one additional effective (barrier) method during study treatment and for 18 months after the end of study treatment.
8. Positive serological test for human immunodeficiency virus (HIV) or active Hepatitis C Virus (HCV; RNA polymerase chain reaction \[PCR\]-positive) or active Hepatitis B Virus (HBV; DNA PCR-positive) infection or any uncontrolled active systemic infection. Subjects with PCR-negative HBV and HCV are permitted in the study.
9. Legal incapacity.
10. Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of Ibrutinib capsules, or put the study outcomes at undue risk.
11. Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial.