Bendamustine + Pomalidomide + Dex in R/R Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Duke University
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Cristina Gasparetto, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT01754402
First received: November 27, 2012
Last updated: August 4, 2014
Last verified: August 2014
  Purpose

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 4 milligrams (mg) on day 1-21, every 28 days and dexamethasone 20 (or 40) mg on days 1, 8, 15, and 22 every 28 days until time of progression.


Condition Intervention Phase
Multiple Myeloma
Drug: Bendamustine
Drug: Pomalidomide
Drug: Dexamethasone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I-II Study of the Combination of Bendamustine and Pomalidomide With Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Maximum tolerated dose level [ Time Frame: 4 weeks after starting the study drug ] [ Designated as safety issue: Yes ]
    In the phase I dose escalation portion, patients will be sequentially enrolled in 4 cohorts at dose levels defined in section 3.1 in a standard 3+3 design until the maximum tolerated dose (MTD) is reached. 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). Up to 24 patients will be enrolled in phase I portion.

  • Response Rate [ Time Frame: best response with up to a minimum of 2 cycles of therapy ] [ Designated as safety issue: No ]
    Response rate (complete response + partial response) - number of patients achieving a complete response or partial response


Secondary Outcome Measures:
  • Overall response rate [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
    the number of patients achieving stable disease (SD), minimal response/minor response (MR), partial response (PR), very good partial response (VGPR), complete response (CR) or stringent complete response (sCR)

  • Time to progression [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
    Time to progression - defined as time elapsed in patients between achievement of response and disease progression

  • Time to next therapy [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
    Time to next Therapy - defined as the time elapsed for patients from initiation of study therapy until initiation of next therapy

  • Progression free survival [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
    The time elapsed for patients between initiation of study therapy and either disease progression or death


Estimated Enrollment: 56
Study Start Date: January 2013
Estimated Study Completion Date: January 2023
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bendamustine+Pomalidomide+Dexamethasone

Study treatment:

  • 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

After 6 cycles of treatment, dexamethasone may be decreased to 20mg. After total 12 cycles of treatment, subjects will proceed to the maintenance phase until time of progression:

  • Pomalidomide 4 mg on day 1-21, every 28 days
  • Dexamethasone 20 (or 40) mg on days 1, 8, 15, and 22 every 28 days .

Study treatment will be administered starting at Cohort 1 for up to four sequential cohorts, with 3-6 patients in each cohort. Once the maximum tolerated dose (MTD) is reached, any additional patients will be enrolled at the MTD level.

Drug: Bendamustine
Bendamustine will be administered intravenously over one hour on day 1, every 28 days for 12 cycles.
Other Name: Treanda
Drug: Pomalidomide
Pomalidomide will be administered once daily orally (PO) on days 1-21, every 28 days until disease progression or death.
Other Names:
  • CC-4047
  • Pomalyst
Drug: Dexamethasone
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.
Other Name: Dexamethasone

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

Patients must meet all of the following inclusion criteria to be eligible to enroll in this study.

  1. Cytopathologically or histologically confirmed diagnosis of multiple myeloma
  2. Relapsed or refractory to most recent therapy (i.e. < 25% response, progression during therapy or within 60 days after completion).
  3. Refractory to prior lenalidomide therapy (i.e. history of progression on therapy using full or maximally tolerated dose of lenalidomide for >/= two cycles).
  4. 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
  5. Evidence of progression/relapse
  6. Over 18
  7. Life expectancy of more than 3 months
  8. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
  9. Total bilirubin < 2 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times ULN
  10. Serum creatinine <3 mg/dL
  11. • 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
    • Platelet count >75.0 x 109/L or < 75.0 x 109/L but >50.0 x 109/L due to >30%* marrow involvement (without platelet transfusions for >1 week)
    • Transfusions allowed if clinically indicated
  12. Agree to take enteric coated aspirin 81 mg daily
  13. Consent
  14. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test and abstain from sex or begin TWO acceptable methods of birth control >28 days before pomalidomide dose, and agree to ongoing pregnancy testing.
  15. Male patients must abstain from sex or use a latex condom and not donate sperm while taking pomalidomide and for 1 week after stopping drug.
  16. Register with POMALYST REMS™ and comply with their requirements.

EXCLUSION CRITERIA:

  1. Patients with known sensitivity to immunomodulatory drugs (IMiDs)
  2. Use of experimental drugs or therapy within 21 days of study-related drug therapy.
  3. Exposure to chemotherapy or steroids within 14 days of study-related drug therapy.
  4. Prior use of pomalidomide.
  5. Radiation therapy within 14 days of screening.
  6. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
  7. Plasma cell leukemia.
  8. Waldenström's macroglobulinemia.
  9. Major surgery within 21 days prior to first dose.
  10. Pregnant or lactating females.
  11. Congestive heart failure, symptomatic ischemia, conduction abnormalities uncontrolled or myocardial infarction in the last six months.
  12. Uncontrolled hypertension
  13. Acute active infection requiring systemic antibiotics, antivirals, or antifungals within 14 days prior to first dose.
  14. Active treatment or intervention for other malignancy or need active treatment within 8 months of starting study treatment.
  15. Serious psychiatric or medical conditions that interfere with treatment
  16. Significant neuropathy (Grade 3, Grade 4) at first dose and/or within 14 days before enrollment
  17. Contraindication to required concomitant drugs
  18. Patients with primary systemic amyloidosis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01754402

Contacts
Contact: Cristina Gasparetto, MD 919-668-1017 gaspa001@mc.duke.edu
Contact: Kimberly Oates, RN 919-668-6524 kimberly.bartlett@duke.edu

Locations
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Principal Investigator: Cristina Gasparetto, MD         
Sponsors and Collaborators
Cristina Gasparetto
Celgene Corporation
Investigators
Principal Investigator: Cristina Gasparetto, MD Duke University
  More Information

No publications provided

Responsible Party: Cristina Gasparetto, Sponsor Investigator, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT01754402     History of Changes
Other Study ID Numbers: Pro00040206, PO-MM-PI-0045
Study First Received: November 27, 2012
Last Updated: August 4, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Duke University:
Multiple Myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Bendamustine
Pomalidomide
Nitrogen Mustard Compounds
Thalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 28, 2014