Pomalidomide Combined With Obinutuzumab in the Treatment of Patients With Relapsed/Refractory Indolent Lymphoma

Official title

A Prospective, Multicenter, Phase I/II Clinical Study of Pomalidomide Combined With Obinutuzumab in the Treatment of Patients With Relapsed/Refractory Indolent Lymphoma.

Overview

To explore the maximum tolerated dose (MTD) of pomalidomide in combination with obinutuzumab in patients with relapsed/refractory indolent lymphomas (including follicular lymphoma, marginal zone lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma) treated with the pomalidomide plus obinutuzumab combination regimen, and to determine the recommended phase II dose (RP2D); concurrently evaluating the efficacy and safety of pomalidomide combined with obinutuzumab in patients with relapsed/refractory indolent lymphomas.

Detailed description

Most indolent B-cell lymphomas have a prolonged natural course with frequent disease relapses, requiring multiple lines of therapy. There is currently no unified standard regimen for relapsed indolent lymphomas, and treatment options are limited for patients who develop resistance to the R2 regimen. Obinutuzumab is a next-generation CD20 monoclonal antibody, while pomalidomide, as a third-generation immunomodulatory drug (IMiDs), exhibits stronger immunomodulatory activity compared to lenalidomide.The Phase I trial evaluated the maximum tolerated dose（MTD） and recommended Phase II dose（RP2D） of the GP regimen (obinutuzumab combined with pomalidomide) in treating relapsed/refractory indolent lymphoma. The Phase II trial assessed the GP regimen, including both induction and maintenance therapy phases, aiming to enhance treatment efficacy, survival rates, and tolerability, thereby providing a novel therapeutic approach for this disease category.

Interventions

• Drug Induction therapy of GP(Pomalidomide+Obinutuzumab）
  Phase 1: Dose Escalation Phase. Obinutuzumab administered at 1000 mg on days 1, 8, and 15 (Cycle 1), and day 1 (Cycles 2-6), with a 28-day cycle. Pomalidomide is administered in three dose groups (2 mg, 3 mg, 4 mg) on days 1-21. Dose-limiting toxicity (DLT) is observed during the first cycle to determine the recommended Phase II dose (RP2D). 2、Phase 2: Dose Expansion Phase. Induction Therapy: Obinutuzumab administered at 1000 mg on days 1, 8, and 15 (Cycle 1), and day 1 (Cycles 2-6), with pomal
• Drug maintenance therapy of GP(Pomalidomide+Obinutuzumab）
  Maintenance Therapy ：Pomalidomide: For complete response (CR) patients, half of the RP2D dose; for PR patients, full RP2D dose, on days 1-21 (Cycles 7-18). Obinutuzumab: 1000 mg administered on day 1 of every 2 cycles

Primary outcome measures

• Recommended Phase II Dose (RP2D) [Time frame: day 28 (each cycle is 28 days)]
• Phase 2 : Objective response rate，ORR [Time frame: Up to the end of 6 cycles of treatment(each cycle is 28 days)]

Secondary outcome measures (4)

• complete response rate，CRR [Time frame: Up to 24 weeks (each cycle is 28 days)]
• progression-free survival，PFS [Time frame: through study completion, an average of 5 year]
• Overall survival，OS [Time frame: through study completion, an average of 5 year]
• Adverse event rate [Time frame: through maintenance therapy completion, an average of 2 years (each cycle is 28 days)]

Eligibility criteria

Inclusion criteria

• Age ≥18 years old, regardless of gender;
• Histopathologically confirmed CD20+ indolent lymphoma (FL, MZL, or SLL), WHO grade 1-3a;.
• Relapsed or refractory disease after at least one prior line of therapy;.
• ECOG-PS 0-2;
• At least one measurable lesion;
• Bone marrow hematopoietic function is basically normal. Complete blood count: white blood cell count >3000/uL, absolute neutrophil count ≥1.5×10\^9/L (use of granulocyte colony-stimulating factor is permitted), platelet count ≥75×10\^9/L (transfusion is allowed to achieve this minimum platelet count), hemoglobin ≥9.0g/dL (prior red blood cell transfusion or use of recombinant human erythropoietin is permitted). If abnormal peripheral blood indices are caused by lymphoma infiltration of bone marrow or spleen, the investigator may exercise discretion in determining eligibility for enrollment.
• Normal function of major organs: Liver function: serum bilirubin ≤2.0×ULN, serum ALT and AST ≤2.5×ULN; Renal function: creatinine clearance >30mL/min;.
• The investigator judged that the expected survival period was ≥3 months;
• The patient was fully informed and signed the informed consent form;.
• Female subjects must use effective contraception, not be pregnant, and agree to practice contraception during the trial and after the study ends. Male subjects must agree to practice contraception during the trial and for 30 days after the last treatment.

Exclusion criteria

• Any other type of lymphoma, including Burkitt lymphoma;
• The investigator confirms that the patient may progress to aggressive lymphoma.
• Patients with contraindications or allergies to the investigational drug.
• History of VTE or cerebral infarction prior to treatment;.
• Patients who have undergone major surgery within 30 days prior to enrollment that may significantly impair physical condition or increase the risk of thrombosis, or who have scheduled surgery during the study period. Subjects planning to undergo minor surgical procedures under local anesthesia that do not significantly affect physical condition or markedly increase thrombosis risk may participate in the study.
• Patients with uncontrolled or severe cardiovascular diseases, including myocardial infarction within 3 months prior to enrollment, unstable coronary artery disease, uncontrolled chronic congestive heart failure, Class III-IV heart failure as defined by the New York Heart Association (NYHA), or clinically significant pericardial disease;.
• Uncontrolled hypertension.
• Uncontrolled diabetes.
• Uncontrolled active infection, or acute active infection, requiring systemic use of antibiotics, antiviral or antifungal medications within two weeks prior to the first dose.
• HIV-positive.
• Active hepatitis B or C.
• History of other malignancies within 3 years prior to the first study drug administration.
• Any clinically significant medical condition or disorder that the investigator considers may affect compliance with the experimental protocol or the subject's ability to provide informed consent.
• The subject is a pregnant or lactating female.
• Patients with severe physical or mental illnesses that may interfere with participation in this clinical study as determined by the protocol or investigator's judgment; or conditions such as drug abuse, medical, psychological, or social circumstances that may affect the subject's participation or evaluation of study results.
• Patients currently receiving other investigational drug treatments.
• Participants who have taken part in other clinical trials within one month.
• Any other patients deemed ineligible for inclusion by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07441954 · IIT2025083

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗