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

Sun Yat-sen University

Status and phase

Unknown

Phase 2

Phase 1

Conditions

Relapsed, Refractory, Multiple Myeloma

Treatments

Drug: Bendamustine

Drug: Pomalidomide

Drug: Dexamethasone

Study type

Interventional

Funder types

Other

Identifiers

NCT04762745

RRMM-01

Details and patient eligibility

About

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

Full 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.

Enrollment

56 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Single Group Assignment

Masking

None (Open label)

56 participants in 4 patient groups

Phase I, Cohort 1

Experimental group

Description:

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).

Treatment:

Drug: Pomalidomide

Drug: Dexamethasone

Drug: Bendamustine

Drug: Pomalidomide

Drug: Dexamethasone

Drug: Bendamustine

Drug: Pomalidomide

Drug: Bendamustine

Drug: Dexamethasone

Drug: Pomalidomide

Drug: Bendamustine

Phase I, Cohort 2

Experimental group

Description:

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).

Treatment:

Drug: Pomalidomide

Drug: Dexamethasone

Drug: Bendamustine

Drug: Pomalidomide

Drug: Dexamethasone

Drug: Bendamustine

Drug: Pomalidomide

Drug: Bendamustine

Drug: Dexamethasone

Drug: Pomalidomide

Drug: Bendamustine

Phase I, Cohort 3

Experimental group

Description:

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).

Treatment:

Drug: Pomalidomide

Drug: Dexamethasone

Drug: Bendamustine

Drug: Pomalidomide

Drug: Dexamethasone

Drug: Bendamustine

Drug: Pomalidomide

Drug: Bendamustine

Drug: Dexamethasone

Drug: Pomalidomide

Drug: Bendamustine

Phase II

Experimental group

Description:

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.

Treatment:

Drug: Pomalidomide

Drug: Dexamethasone

Drug: Bendamustine

Drug: Pomalidomide

Drug: Dexamethasone

Drug: Bendamustine

Drug: Pomalidomide

Drug: Bendamustine

Drug: Dexamethasone

Drug: Pomalidomide

Drug: Bendamustine