Bendamustine + Pomalidomide + Dex in R/R Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 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: January 9, 2014
Last verified: January 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 will be decreased to 20mg. 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 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 will be as follows, in 28 day cycles:

  • Pomalidomide: once daily PO dosing on days 1-21, every 28 days
  • Bendamustine: once 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 will be decreased to 20mg. After completing 12 cycles of treatment, patients will proceed to the maintenance phase of the study. Patients will receive Pomalidomide 4 mg on day 1-21, every 28 days and dexamethasone 20 mg on days 1, 8, 15, and 22 every 28 days until time of progression. Study treatment will be administered starting at Cohort 1 for up to four sequential cohorts, with 3-6 patients in each cohort. A standard 3+ 3 dose escalation schedule will be used. Once the MTD is reached, any additional patients will be enrolled at the MTD level, up to a total of 30 patients.

Drug: Bendamustine
Bendamustine will be Aadministered intravenously over one hour.
Other Name: Treanda
Drug: Pomalidomide
Other Names:
  • CC-4047
  • Pomalyst
Drug: Dexamethasone
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

  Eligibility

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

Inclusion Criteria:

  1. Cytopathologically or histologically confirmed diagnosis of multiple myeloma
  2. Relapsed or refractory to the most recently received therapy. Refractory disease is defined as < 25% response or progression during therapy or within 60 days after completion.
  3. All patients must have received prior lenalidomide therapy and been determined to be refractory. Refractory will be defined as a history of progression on a regimen containing full or maximally tolerated dose of lenalidomide administered for a minimum of at least two completed cycles of therapy.
  4. Measurable disease as specified in the protocol
  5. Prior to enrollment, sites must provide evidence of myeloma progression/relapse and evidence of being refractory to lenalidomide, with start and stop dates of lenalidomide therapy and the most recent treatment regimen, as well as best tumor response to all prior treatment regimens.
  6. Males and females 18 years of age or older
  7. Life expectancy of more than 3 months
  8. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
  9. Adequate hepatic function, with 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. Laboratory tests meet the levels specified in the protocol
  12. Patients must agree to take enteric coated aspirin 81 mg orally daily, or if history of prior thrombotic disease, must be fully anticoagulated with warfarin (INR 2-3) or be treated with full dose, low molecular weight heparin, as if to treat deep venous thrombosis (DVT)/pulmonary embolism (PE)
  13. Written informed consent in accordance with federal, local, and institutional guidelines
  14. Females of Child Bearing Potential (FCBP) must meet requirements for pregnancy testing and use approved methods of contraception.
  15. Male patients must use approved methods of contraception.
  16. All study participants must be registered into the mandatory POMALYST REMS™ program, and be willing and able to comply with the requirements of the POMALYST REMS™ program.

Exclusion Criteria:

  1. Patients with known sensitivity to any immunomodulatory drugs (IMiDs)
  2. Use of any other experimental drugs or therapy within 21 days of study-related drug therapy.
  3. Exposure to any prior chemotherapy or steroids use within 14 days of screening assessment. (steroids use allowed if necessary to treat spinal cord compression).
  4. Any prior use of bendamustine.
  5. Any prior use of pomalidomide.
  6. Radiation therapy within 14 days of screening.
  7. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
  8. Plasma cell leukemia.
  9. Waldenström's macroglobulinemia.
  10. Major surgery within 21 days prior to first dose.
  11. Pregnant or lactating females.
  12. Congestive heart failure (New York Heart Association class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention or myocardial infarction in the previous six months.
  13. Uncontrolled hypertension
  14. Acute active infection requiring systemic antibiotics, antivirals, or antifungals within 14 days prior to first dose.
  15. Patients receiving active treatment or intervention for any other malignancy or patients who, at the investigator's discretion, may require active treatment or intervention for any other malignancy within 8 months of starting study treatment.
  16. Serious psychiatric or medical conditions that could interfere with treatment
  17. Significant neuropathy (Grade 3, Grade 4) at the time of the first dose and/or within 14 days before enrollment
  18. Contraindication to any of the required concomitant drugs, including, including proton pump inhibitor (e.g. lansoprazole), enteric coated aspirin or if a history of prior thrombotic disease, warfarin or low molecular weight heparin
  19. 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: January 9, 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
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
Gastrointestinal Agents

ClinicalTrials.gov processed this record on July 26, 2014