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

NCT04762745 | Unknown Phase 1

• 1 other identifier: RRMM-01
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Relapsed, Refractory, Multiple Myeloma

Keywords

pomalidomide, bendamustine, multiple myeloma

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  The number of patients achieving partial response (PR), very good partial response (VGPR), complete response (CR) or stringent complete response (sCR) after 8 cycles in phase II. sCR = CR as defined in Primary Outcome measure 2 plus normal free light chain ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. CR- Negative immunofixation on serum and urine and disappearance of soft tissue plasmacytomas and \< 5% plasma cells in bone marrow. VGPR = Serum and urine M-protein detectable by immunofixation but not on electrophoresis or \> 90% reduction in serum M-protein plus urine M-protein level \< 100 mg/24 h. PR- \> 50% reduction of serum M-protein and urine M-protein by \>90% or to \< 200 mg/24 h In addition, if present at baseline, a \> 50% reduction in the size of soft tissue plasmacytomas is also required.

  At the end of Cycle 8 in Phase II (each cycle is 28 days)

Secondary Outcomes (3)

• Complete response(CR) and stringent complete response(sCR) rate

  At the end of Cycle 8 in Phase II (each cycle is 28 days)

• Progression free survival(PFS)

  Through study completion, up to 2 years

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Through study completion, up to 2 years

Study Arms (4)

Phase I, Cohort 1

EXPERIMENTAL

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).

Drug: Pomalidomide; Drug: Bendamustine; Drug: Dexamethasone

Phase I, Cohort 2

EXPERIMENTAL

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).

Drug: Pomalidomide; Drug: Bendamustine; Drug: Dexamethasone

Phase I, Cohort 3

EXPERIMENTAL

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).

Drug: Pomalidomide; Drug: Bendamustine; Drug: Dexamethasone

Phase II

EXPERIMENTAL

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.

Drug: Pomalidomide; Drug: Bendamustine; Drug: Dexamethasone

Interventions

Pomalidomide DRUG

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

Also known as: Pomalidomide( Anyue®, Chia Tai TIANQING, China)

Phase I, Cohort 1

Bendamustine DRUG

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

Also known as: Bendamustine( Leweixin®, Chia Tai TIANQING, China)

Phase I, Cohort 1

Dexamethasone DRUG

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

Phase I, Cohort 1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Please Select, 510060, China

Location

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Interventions

pomalidomide; Bendamustine Hydrochloride; Dexamethasone

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor of Department of Hematological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

Study Record Dates

• First Submitted: February 16, 2021
• First Posted: February 21, 2021
• Study Start: February 1, 2021
• Primary Completion: February 1, 2022
• Study Completion: February 1, 2023
• Last Updated: February 21, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)