Dose Finding Study of Ibrutinib Plus Lenalidomide / Rituximab in Relapsed or Refractory Mantle Cell Lymphoma

• Status: Active, not recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a dose-escalation to determine the MTD and/or RPII for combinations of ibrutinib (PCI-32765) plus lenalidomide/rituximab in patients with relapsed/refractory mantle cell lymphoma.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hackensack Meridian Health; Hackensack University Medical Center
• Treatments: Lenalidomide; Rituximab; Thalidomide

Criteria

Inclusion Criteria:

• Age greater than or equal to 18 years.

• Histologically or cytologically confirmed diagnosis of MCL.

• Relapsed or refractory MCL patients who have received at least one prior therapy are eligible. Patients who have previously received high-dose chemotherapy with peripheral stem cell support are eligible.

• Presence of at least one lymph node evaluable or mass measurable for response.

• Eastern Cooperative Oncology Group Performance Status greater than 2.

• Platelets > 75,000/μL and absolute neutrophils count (ANC) > 1,000/μL within 14 days of study registration (unless the treating physician deems the neutropenia is related to bone marrow involvement, then an ANC of > 750/mm 3 is allowed)

• Normal renal function defined as serum creatinine less than 2.

• Recovery from any previous treatment therapy.

• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test

• All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of the REMS® program.

• Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program.

• Ability to understand, and willingness to sign, a written informed consent document.

• Able to take aspirin (81 or 325 mg) daily as prophylactic anti-coagulation (patients intolerant to ASA may use low molecular weight heparin).

• Normal organ and bone marrow function parameter:

Laboratory tests Required value WBC >3000/μL* Absolute neutrophils count >1,000/μL* Platelets >75,000/μL Total bilirubin < 1.5Within normal institutional limits AST (SGOT) and ALT (SGPT) <3 x institutional upper limit of normal Creatinine or creatinine clearance <1.5 within normal institutional limits >60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal (calculated by Cockcroft-Gault formula)

Exclusion Criteria:

• Concomitant use of warfarin or other Vit K antagonists

• Central nervous system (CNS) involvement by lymphoma at time of enrollment.

• Other medical conditions that would potentially interfere with patient participation in this trial.

• A second malignancy, other than basal cell carcinoma of the skin or in situ carcinoma of the cervix (unless for other tumor type patient was treated with curative intent at least 2 years previously.)

• Known human immunodeficiency virus (HIV-1) infection or chronic hepatitis B, or C (Hep B serology positive without active infection will be eligible)

• Active, clinically serious infection > CTCAE grade 2. Patients may be eligible upon resolution of the infection.

• Major surgery or significant traumatic injury within 28 days of the first dose of study drug.

• Use of any other standard chemotherapy, radiation therapy, or experimental drug therapy for the treatment of MCL within 21 days of starting treatment or 5 half life times (whatever is shorter)

• Patients with grade 3/4 cardiac problems, as defined by the New York Heart Association (NYHA) criteria:

• History of uncontrolled or symptomatic angina

• History of uncontrolled arrhythmias

• Myocardial infarction < 6 months from study entry

• Uncontrolled or symptomatic congestive heart failure

• Ejection fraction below the institutional normal limit

• Any other cardiac condition that, in the opinion of the treatment physician, would make this protocol unreasonably hazardous for the patient

• Patients unwilling or unable to comply with the protocol.