Study to Determine the Maximum Tolerated Dose for the Combination of Pomalidomide, Bortezomib and Low-Dose Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Celgene Corporation
Sponsor:
Collaborator:
Multiple Myeloma Research Consortium
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01497093
First received: December 20, 2011
Last updated: April 17, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to determine the maximum tolerated dose (MTD) of pomalidomide in combination with bortezomib and low-dose dexamethasone in subjects with relapsed or refractory multiple myeloma


Condition Intervention Phase
Multiple Myeloma
Drug: Pomalidomide
Drug: Bortezomib
Drug: Dexamethasone
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1, Multicenter, Open-Label, Dose-escalation Study to Determine the Maximum Tolerated Dose for the Combination of Pomalidomide, Bortezomib and Low-Dose Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Maximum Tolerated Dose [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    To determine the maximum tolerated dose (MTD)


Secondary Outcome Measures:
  • Adverse events [ Time Frame: Up to 7 years ] [ Designated as safety issue: Yes ]
    Number of participants with adverse events (AEs)

  • Overall Survival [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    Number of patients alive

  • Response Rate [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    Overall response rate based on the International Myeloma Working Group (IMWG) Uniform response criteria

  • Duration of response [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    Time from the initial documented response to confirmed disease progression

  • Time to response [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    Time from enrollment to the first documented response


Estimated Enrollment: 48
Study Start Date: December 2011
Estimated Study Completion Date: September 2019
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pomalidomide/Bortezomib/Dexamethasone
1, 2, 3 or 4 mg of pomalidomide will be taken orally on Days 1-14 of a 21-day cycle along with 1 or 1.3 mg/m2 of bortezomib administered intravenously or subcutaneously on Days 1, 4, 8 and 11 of 21 days for cycles 1 -8 and on days 1, 8 of 21 days for cycle 9 and onward until disease progression, and dexamethasone 20 mg/day [≤ 75 years old] or 10 mg/day [> 75 years old] orally on days 1, 2, 4, 5, 8, 9, 11, 12 of 21 days for cycles 1-8 and on days 1, 2, 8, 9 of 21 days for cycles 9 and onward until disease progression
Drug: Pomalidomide
Pomalidomide 1, 2, 3, or 4 mg will be taken orally on Days 1-14 of a 21-day cycle
Other Names:
  • CC-4047
  • Oral Pomalidomide
Drug: Bortezomib
Bortezomib 1 or 1.3 mg/m2 will be administered intravenously or subcutaneously on Days 1, 4, 8 and 11 of 21 days for cycles 1 -8 and on days 1, 8 of 21 days for cycle 9 and onward until disease progression
Other Name: Velcade
Drug: Dexamethasone
Dexamethasone 20 mg/day [≤ 75 years old] or 10 mg/day [> 75 years old] will be taken orally on days 1, 2, 4, 5, 8, 9, 11, 12 of 21 days for cycles 1-8 and on days 1, 2, 8, 9 of 21 days for cycles 9 and onward until disease progression

Detailed Description:

A 3 + 3 design will be utilized to determine the MTD for POM + IV BTZ + LD-DEX combination treatment in a 21-day treatment cycle. DLT will be assessed to determine MTD during the first treatment cycle. Once the MTD is determined or the maximum planned dose (MPD) is reached without reaching MTD for POM + IV BTZ + LD-DEX, a cohort of 6 additional subjects will be treated at this MTD/MPD level to further confirm the safety and assess preliminary efficacy. An additional cohort of subjects will be enrolled to explore the safety for the combination of POM + BTZ + LD-DEX when using SQ BTZ. Subject in this cohort will receive POM + BTZ + LD-DEX at the MTD/MPD level per the MTD determination part of the study, except, the BTZ will be administered subcutaneously (SQ) instead of intravenously (IV). In, Protocol Amendment #4, the number of subject enrolled to be enrolled into the exploratory SQ BTZ cohort was increased from 6 to 12.

  Eligibility

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

Inclusion criteria:

  1. Must be ≥ 18 years at the time of signing the informed consent form.
  2. Subjects must have documented diagnosis of multiple myeloma and have measurable disease (serum M-protein ≥ 0.5 g/dL or urine M-protein ≥ 200 mg/24 hours).
  3. Subjects must have had at least 1 but no greater than 4 prior anti-myeloma therapies.
  4. Subjects must have received at least 2 consecutive cycles of prior treatment with lenalidomide and must be refractory to their last lenalidomide-containing regimen (either as a single agent or in combination).
  5. Subjects must have received at least 2 consecutive cycles of prior treatment with a proteasome inhibitor-containing regimen, but must not be refractory to bortezomib (either as a single agent or in combination).
  6. Subjects must have documented progression during or after their last anti-myeloma therapy.
  7. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.

Exclusion criteria:

  1. Subjects who are refractory to bortezomib either as single agent or in combination.
  2. Subjects with peripheral neuropathy ≥ Grade 2
  3. Subjects with non-secretory multiple myeloma
  4. Subjects with any of the following laboratory abnormalities:

    • Absolute neutrophil count (ANC) < 1,000/µL
    • Platelet count < 75,000/µL for subjects in whom < 50% of bone marrow nucleated cells are plasma cells; or a platelet count < 30,000/ µL for subjects in whom ≥ 50% of bone marrow nucleated cells are plasma cells
    • Creatinine Clearance < 45 mL/min according to Cockcroft-Gault formula
    • Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L)
    • Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior RBC transfusion or recombinant human erythropoietin use is permitted)
    • Serum glutamic oxaloacetic transaminase (SGOT)/ aspartate aminotransferase (AST) or Transaminase, serum glutamic pyruvic (SGPT)/ alanine aminotransferase (ALT) > 3.0 x upper limit of normal (ULN)
    • Serum total bilirubin > 1.5 x ULN
  5. Subjects with prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years. Except the following: Basal cell carcinoma of the skin, Squamous cell carcinoma of the skin, Carcinoma in situ of the cervix, Carcinoma in situ of the breast, Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is curative.
  6. Subjects with previous therapy with Pomalidomide
  7. Subjects with hypersensitivity to thalidomide, lenalidomide, bortezomib, boron, mannitol, or dexamethasone
  8. Subjects with ≥ Grade 3 rash during prior thalidomide or lenalidomide therapy
  9. Subjects who had any of the following within the last 14 days of initiation of study treatment: Plasmapheresis, Major surgery (kyphoplasty is not considered major surgery), Radiation therapy, Any anti-myeloma drug therapy
  10. Subjects who have received any investigational agents within 28 days or 5 half-lives (whichever is longer) of treatment
  11. Pregnant or breastfeeding females
  12. Men or women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception.
  13. Subjects with known Human immunodeficiency virus (HIV) positivity or active infectious hepatitis A, B, or C
  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: NCT01497093

Contacts
Contact: Tomoko Mays 908-673-2238 tsmays@celgene.com
Contact: Associate Director, Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com

Locations
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
United States, New Jersey
John Theurer Cancer Center - Hackensack University Recruiting
Hackensack, New Jersey, United States, 07602
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Celgene Corporation
Multiple Myeloma Research Consortium
Investigators
Study Director: Mohamed Zaki, MD, PhD Celgene Corporation
  More Information

No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01497093     History of Changes
Other Study ID Numbers: CC-4047-MM-005
Study First Received: December 20, 2011
Last Updated: April 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Celgene Corporation:
Myeloma
Multiple Myeloma
Relapsed Multiple Myeloma
Relapsed and Refractory Multiple Myeloma
Refractory Myeloma
Resistant Multiple Myeloma
Treatment-resistant Multiple Myeloma
Pomalidomide
Lenalidomide-resistant

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
Bortezomib
Pomalidomide
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 August 28, 2014