The Efficacy and Safety of Pomalidomide and Bendamustine With Dexamethasone in Relapsed or Refractory Multiple Myeloma

NCT ID: NCT04762745

Last Updated: 2021-02-21

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-28
• Study Completion Date: 2023-02-28

Brief Summary

To explore the efficacy and safety of pomalidomide and bendamustine with dexamethasone in relapsed or refractory multiple myeloma

Detailed Description

The trial has two parts: firstly, to explore the maximum tolerated dosage(MTD) of bendamustine in the combination of pomalidomide and dexamethasone in relapsed or refractory multiple myeloma; secondly, to find out efficacy and safety of pomalidomide and bendamustine with dexamethasone in relapsed or refractory multiple myeloma in an expanded cohort.

Conditions

Relapsed, Refractory, Multiple Myeloma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase I, Cohort 1

The combination of bendamustine, 60mg/m2, with pomalidomide and dexamethasone will be administrated in 6 relapsed or refractory multiple myeloma patients for 1 cycle. If dose limiting toxicity (DLT) is observed in 2 or more of the six patients at the same dosing level while DLT is observed in only 1 or none of the 6 patients at the dosing level immediately below it, then the lower dosing level will be defined as the maximum tolerated dose (MTD).

Group Type: EXPERIMENTAL

Pomalidomide

Intervention Type: DRUG

Pomalidomide( Anyue®, Chia Tai TIANQING, China), 4mg, orally(PO), d1-21, 28d/cycle, 1cycle.

Bendamustine

Intervention Type: DRUG

Bendamustine( Leweixin®, Chia Tai TIANQING, China), 60mg/m2/d, intravenously(IV), d1-2, 28d/cycle, 1 cycle.

Dexamethasone

Intervention Type: DRUG

Dexamethasone, 40mg, PO or IV, d1, 8, 15, 22, 28d/cycle, 1 cycle.

Phase I, Cohort 2

The combination of bendamustine, 70mg/m2, with pomalidomide and dexamethasone will be administrated in 6 relapsed or refractory multiple myeloma patients for 1 cycle. If dose limiting toxicity (DLT) is observed in 2 or more of the six patients at the same dosing level while DLT is observed in only 1 or none of the 6 patients at the dosing level immediately below it, then the lower dosing level will be defined as the maximum tolerated dose (MTD).

Group Type: EXPERIMENTAL

Pomalidomide

Intervention Type: DRUG

Pomalidomide( Anyue®, Chia Tai TIANQING, China), 4mg, orally(PO), d1-21, 28d/cycle, 1cycle.

Bendamustine

Intervention Type: DRUG

Bendamustine( Leweixin®, Chia Tai TIANQING, China), 70mg/m2/d, intravenously(IV), d1-2, 28d/cycle, 1 cycle.

Dexamethasone

Intervention Type: DRUG

Dexamethasone, 40mg, PO or IV, d1, 8, 15, 22, 28d/cycle, 1 cycle.

Phase I, Cohort 3

The combination of bendamustine, 80mg/m2, with pomalidomide and dexamethasone will be administrated in 6 relapsed or refractory multiple myeloma patients for 1 cycle. If dose limiting toxicity (DLT) is observed in 2 or more of the six patients at the same dosing level while DLT is observed in only 1 or none of the 6 patients at the dosing level immediately below it, then the lower dosing level will be defined as the maximum tolerated dose (MTD).

Group Type: EXPERIMENTAL

Pomalidomide

Intervention Type: DRUG

Pomalidomide( Anyue®, Chia Tai TIANQING, China), 4mg, orally(PO), d1-21, 28d/cycle, 1cycle.

Bendamustine

Intervention Type: DRUG

Bendamustine( Leweixin®, Chia Tai TIANQING, China), 70mg/m2/d, intravenously(IV), d1-2, 28d/cycle, 1 cycle.

Dexamethasone

Intervention Type: DRUG

Dexamethasone, 40mg, PO or IV, d1, 8, 15, 22, 28d/cycle, 1 cycle.

Phase II

The combination of MTD dosage of bendamustine with pomalidomide and dexamethasone will be administrated in an expanded relapsed or refractory multiple myeloma cohorts for 8 cycles, then under the combination of pomalidomide and dexamethasone as maintenance therapy until progression or intolerable toxicities.

Group Type: EXPERIMENTAL

Pomalidomide

Intervention Type: DRUG

Pomalidomide( Anyue®, Chia Tai TIANQING, China), 4mg, orally(PO), d1-21, 28d/cycle, 8 cycles. Then pomalidomide( Anyue®, Chia Tai TIANQING, China), 4mg, orally(PO), d1-21, 28d/cycle until progression or intolerable toxicities.

Bendamustine

Intervention Type: DRUG

Bendamustine( Leweixin®, Chia Tai TIANQING, China), 70mg/m2/d, intravenously(IV), d1-2, 28d/cycle, 8 cycles.

Dexamethasone

Intervention Type: DRUG

Dexamethasone, 40mg, PO or IV, d1, 8, 15, 22, 28d/cycle, 8 cycles. Then dexamethasone, 40mg, PO or IV, d1, 8, 15, 22, 28d/cycle until progression or intolerable toxicities.

Interventions

Pomalidomide

Pomalidomide( Anyue®, Chia Tai TIANQING, China), 4mg, orally(PO), d1-21, 28d/cycle, 1cycle.

Intervention Type: DRUG

Bendamustine

Bendamustine( Leweixin®, Chia Tai TIANQING, China), 60mg/m2/d, intravenously(IV), d1-2, 28d/cycle, 1 cycle.

Intervention Type: DRUG

Dexamethasone

Dexamethasone, 40mg, PO or IV, d1, 8, 15, 22, 28d/cycle, 1 cycle.

Intervention Type: DRUG

Pomalidomide

Pomalidomide( Anyue®, Chia Tai TIANQING, China), 4mg, orally(PO), d1-21, 28d/cycle, 1cycle.

Intervention Type: DRUG

Bendamustine

Bendamustine( Leweixin®, Chia Tai TIANQING, China), 70mg/m2/d, intravenously(IV), d1-2, 28d/cycle, 1 cycle.

Intervention Type: DRUG

Dexamethasone

Dexamethasone, 40mg, PO or IV, d1, 8, 15, 22, 28d/cycle, 1 cycle.

Intervention Type: DRUG

Pomalidomide

Pomalidomide( Anyue®, Chia Tai TIANQING, China), 4mg, orally(PO), d1-21, 28d/cycle, 1cycle.

Intervention Type: DRUG

Bendamustine

Bendamustine( Leweixin®, Chia Tai TIANQING, China), 70mg/m2/d, intravenously(IV), d1-2, 28d/cycle, 1 cycle.

Intervention Type: DRUG

Dexamethasone

Dexamethasone, 40mg, PO or IV, d1, 8, 15, 22, 28d/cycle, 1 cycle.

Intervention Type: DRUG

Pomalidomide

Pomalidomide( Anyue®, Chia Tai TIANQING, China), 4mg, orally(PO), d1-21, 28d/cycle, 8 cycles. Then pomalidomide( Anyue®, Chia Tai TIANQING, China), 4mg, orally(PO), d1-21, 28d/cycle until progression or intolerable toxicities.

Intervention Type: DRUG

Bendamustine

Bendamustine( Leweixin®, Chia Tai TIANQING, China), 70mg/m2/d, intravenously(IV), d1-2, 28d/cycle, 8 cycles.

Intervention Type: DRUG

Dexamethasone

Dexamethasone, 40mg, PO or IV, d1, 8, 15, 22, 28d/cycle, 8 cycles. Then dexamethasone, 40mg, PO or IV, d1, 8, 15, 22, 28d/cycle until progression or intolerable toxicities.

Intervention Type: DRUG

Other Intervention Names

Pomalidomide( Anyue®, Chia Tai TIANQING, China); Bendamustine( Leweixin®, Chia Tai TIANQING, China); Pomalidomide( Anyue®, Chia Tai TIANQING, China); Bendamustine( Leweixin®, Chia Tai TIANQING, China); Pomalidomide( Anyue®, Chia Tai TIANQING, China); Bendamustine( Leweixin®, Chia Tai TIANQING, China); Pomalidomide( Anyue®, Chia Tai TIANQING, China); Bendamustine( Leweixin®, Chia Tai TIANQING, China)

Eligibility Criteria

Inclusion Criteria

• Age of 18-75, no gender limitations.
• Ability of contraception during the experiment, no matter if they have suffered from infertility.
• Relapsed or refractory to prior lenalidomide or/and bortezomib(either in combination or sequential)therapy (i.e. history of progression on therapy or within 60 days after completion)
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2, life expectancy of more than 6 months.
• Measurable disease:

Serum M protein > 10 g/L or Urine M protein ≥200 mg/24 hr or Elevated Free Light Chain per International Myeloma Working Group (IMWG) criteria, and abnormal ratio.

• Absolute neutrophil count (ANC) >1.0 x 109/L or >1.0 x 109/L due to granulocyte/macrophage colony stimulating factor (GCSF and GMCSF), or if >50% marrow involvement, there is no limitations
• Platelet count >50.0 x 109/L or if >50% marrow involvement, there is no limitations.
• Total bilirubin ≤ 2.0mg/dL, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times the upper limit of normal.
• Serum creatinine ≤2.0 mg/dL or creatinine clearance ≥60ml/min.
• Agree to take anticoagulant drugs, included but not limited to aspirin.
• Agree to sign the informed consent form.

Exclusion Criteria

• Patients with known sensitivity to pomalidomide or bendamustine or dexamethasone and their accessories.
• Patients with primary systemic amyloidosis or monoclonal gammopathy of undetermined significance or smoldering multiple myeloma.
• Patients with active new thrombosis or disagree to take anticoagulant drugs, included but not limited to aspirin.
• Active treatment or intervention for other malignancy or need active treatment within 4 weeks of starting study treatment. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• Central nervous system involvement.
• Systemic treatment with immunodepressants or steroids.
• Ongoing or active systemic infection, active hepatitis B virus infect, active hepatitis C infection, or known human immunodeficiency virus (HIV) positive
• Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure(NT-Pro-BNP≥1800pg/mL), unstable angina, or myocardial infarction within the past 6 months.
• Infection requiring systemic antibiotic therapy or other serious infection.
• Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens. Psychiatric illness/social situation that would limit compliance with study requirements.
• Under other clinical trial procedures.
• Female patients who are lactating or pregnant.
• Other patients not appropriate for the trial in the judgment of the investigator.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Hua Wang

Associate professor of Department of Hematological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Sun Yat-sen University Cancer Center

Guangzhou, Please Select, China

Countries

China

Other Identifiers

RRMM-01

Identifier Type: -

Identifier Source: org_study_id