Bendamustine + Pomalidomide + Dex in R/R Multiple Myeloma

NCT01754402 | Unknown Phase 1 Results FDA Drug

• 2 other identifiers: Pro00040206PO-MM-PI-0045
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed as a phase I-II, open label, dose finding study. Study treatment will be as follows, in 28 day cycles:

• Pomalidomide: once daily orally (PO) dosing on days 1-21, every 28 days
• Bendamustine: once intravenously (IV) dosing on day 1, every 28 days
• Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22. After completing 6 cycles of treatment, dexamethasone may be decreased to 20mg per investigator discretion. After completing 12 cycles of treatment, patients will proceed to the maintenance phase of the study. Patients will receive Pomalidomide on day 1-21, every 28 days and dexamethasone on days 1, 8, 15, and 22 every 28 days until time of progression.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose of Pomalidomide and Bendamustine

  In the phase I dose escalation portion, patients will be sequentially enrolled in 4 cohorts at dose levels in a standard 3+3 design until the maximum tolerated dose (MTD) is reached. Cohort 1 (bendamustine 120mg/m2 + pomalidomide 3mg); Cohort 2 (bendamustine 120mg/m2 + pomalidomide 4mg); Cohort 3 (bendamustine 150mg/m2 + pomalidomide 4mg); Cohort 4 (bendamustine 180mg/m2 + pomalidomide 4mg) 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).

  2 cycles (approximately 2 months)

• Initial Response Rate

  The number of patients achieving a complete response (CR) or partial response (PR). Response is defined by the International Myeloma Working Group as: CR- Negative immunofixation on serum and urine and disappearance of soft tissue plasmacytomas and \< 5% plasma cells in bone marrow 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 VGPR - Serum and urine M-protein detectable by immunofixation but n

  2 cycles (approximately 2 months)

Secondary Outcomes (4)

• Overall Response Rate

  2 years after last dose of study drug

• Time to Progression

  2 years after last dose of study drug

• Time to Next Therapy

  2 years after last dose of study drug

• Progression Free Survival

  2 years after last dose of study drug

Study Arms (3)

Cohort 1: benda 120mg + pom 3mg

EXPERIMENTAL

* Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days * Bendamustine: once intravenous (IV) dosing on day 1, every 28 days * Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days

Drug: Bendamustine; Drug: Pomalidomide; Drug: Dexamethasone

Cohort 2: benda 120mg + pom 4mg

EXPERIMENTAL

* Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days * Bendamustine: once intravenous (IV) dosing on day 1, every 28 days * Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days

Drug: Bendamustine; Drug: Pomalidomide; Drug: Dexamethasone

Expansion

EXPERIMENTAL

* Pomalidomide 3mg: once daily oral (PO) dosing on days 1-21, every 28 days * Bendamustine 120 mg: once intravenous (IV) dosing on day 1, every 28 days * Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days

Drug: Bendamustine; Drug: Pomalidomide; Drug: Dexamethasone

Interventions

Bendamustine DRUG

Bendamustine will be administered intravenously over 1 hour (if using Treanda) or over 10 minutes (if using Bendeka) on day 1, every 28 days for 12 cycles.

Also known as: Treanda, Bendeka

Cohort 1: benda 120mg + pom 3mg; Cohort 2: benda 120mg + pom 4mg; Expansion

Pomalidomide DRUG

Pomalidomide will be administered once daily orally (PO) on days 1-21, every 28 days until disease progression or death.

Also known as: CC-4047, Pomalyst

Cohort 1: benda 120mg + pom 3mg; Cohort 2: benda 120mg + pom 4mg; Expansion

Dexamethasone DRUG

Dexamethasone will be administered weekly orally or intravenously on days 1, 8, 15, and 22 every 28 days until disease progression or death. After 6 cycles of treatment, the dose may be reduced to 20mg at investigator's discretion. For subjects ≥ 75 years of age, the starting dose of dexamethasone is 20 mg/day on Days 1, 8, 15 and 22 of each 28-day treatment cycle.

Cohort 1: benda 120mg + pom 3mg; Cohort 2: benda 120mg + pom 4mg; Expansion

Eligibility Criteria

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

You may qualify if:

• Cytopathologically or histologically confirmed diagnosis of multiple myeloma
• Relapsed or refractory to most recent therapy (i.e. \< 25% response, progression during therapy or within 60 days after completion).
• Refractory to prior lenalidomide therapy (i.e. history of progression on therapy using full or maximally tolerated dose of lenalidomide for \>/= two cycles).
• Measurable disease:
• Serum M protein \> 0.5 g/dL or
• Urine Bence Jones protein \>200 mg/24 hr or
• Elevated Free Light Chain per International Myeloma Working Group (IMWG) criteria, and abnormal ratio
• Evidence of progression/relapse
• Over 18
• Life expectancy of more than 3 months
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
• Total bilirubin \< 2 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 times ULN
• Serum creatinine \<3 mg/dL
• Absolute neutrophil count (ANC) \>1.0 x 109/L or \<1.0 x 109/L but \> 0.75 due to \>30%\* marrow involvement (without granulocyte and granulocyte/macrophage colony stimulating factor (GCSF and GMCSF) for \>1 week and of pegylated GCSF for \>2 weeks)
• Hemoglobin \>8 g/dL

You may not qualify if:

• Patients with known sensitivity to immunomodulatory drugs (IMiDs)
• Use of experimental drugs or therapy within 21 days of study-related drug therapy.
• Exposure to chemotherapy or steroids within 14 days of study-related drug therapy.
• Prior use of pomalidomide.
• Radiation therapy within 14 days of screening.
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
• Plasma cell leukemia.
• Waldenström's macroglobulinemia.
• Major surgery within 21 days prior to first dose.
• Pregnant or lactating females.
• Congestive heart failure, symptomatic ischemia, conduction abnormalities uncontrolled or myocardial infarction in the last six months.
• Uncontrolled hypertension
• Acute active infection requiring systemic antibiotics, antivirals, or antifungals within 14 days prior to first dose.
• Active treatment or intervention for other malignancy or need active treatment within 8 months of starting study treatment.
• Serious psychiatric or medical conditions that interfere with treatment

Sponsors & Collaborators

• Cristina Gasparetto: lead
• Celgene: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bendamustine Hydrochloride; pomalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Cristina Gasparetto, MD
• Organization: Duke University Medical Center

cristina.gasparetto@duke.edu

919-668-1017

Study Officials

• Gwynn Long, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Model Details: Dose escalation with 3+3 cohort design plus Dose expansion at the Maximum tolerated dose.

Study Record Dates

• First Submitted: November 27, 2012
• First Posted: December 21, 2012
• Study Start: January 7, 2013
• Primary Completion: December 6, 2016
• Study Completion: January 1, 2025
• Last Updated: February 20, 2024
• Results First Posted: February 27, 2017

Record last verified: 2024-01

Locations

US (1)