CC-4047 and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma or Amyloidosis

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00558896
First received: November 14, 2007
Last updated: May 28, 2014
Last verified: May 2014
  Purpose

RATIONALE: Biological therapies, such as CC-4047, may stimulate the immune system in different ways and stop cancer cells from growing. Dexamethasone and CC-4047 may stop the growth of cancer cells by blocking blood flow to the cancer. Giving CC-4047 together with dexamethasone may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving CC-4047 together with dexamethasone works in treating patients with relapsed or refractory multiple myeloma or amyloidosis.


Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Drug: dexamethasone
Drug: pomalidomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of CC-4047 Plus Dexamethasone in Patients With Relapsed of Refractory Multiple Myeloma or Amyloidosis

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • The Number of Confirmed Hematologic Responses (Complete, Partial, or Very Good Partial Response) [ Time Frame: Duration of study (up to 3 years) ] [ Designated as safety issue: No ]

    Response that was confirmed on 2 consecutive evaluations

    • Complete Response(CR): Complete disappearance of M-protein from serum and urine on immunofixation, normalization of Free Light Chain (FLC) ratio and <5% plasma cells in bone marrow.
    • Very Good Partial Response(VGPR): >=90% reduction in serum M-component; Urine M-Component <100mg per 24hours; <=5% plasma cells in bone marrow.
    • Partial Response(PR): >=50% reduction in serum M-component and/or Urine M-Component >=90% reduction or <200mg per 24hours; or >=50% decrease in difference between involved and uninvolved FLC levels.


Secondary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: Duration of study (up to 5 years) ] [ Designated as safety issue: No ]

    PFS was defined as the time from registration to progression or death due to any cause. PFS was analyzed using Kaplan Meier method.

    Progression was defined as any one or more of the following:

    • 25% increase in serum M-component (absolute increase >= 0.5g/dl)
    • 25% increase in urine M-component (absolute increase >= 200mg/24hour
    • 25% increase in the difference between involved and uninvolved Free Light Chain levels (absolute increase >= 10mg/dl)
    • 25% increase in bone marrow plasma cell percentage (absolute increase of >=10%)
    • Definite development of new bone lesion or soft tissue plasmacytomas

  • Duration of Response [ Time Frame: Duration of study (up to 5 years) ] [ Designated as safety issue: No ]
    Duration of response was calculated from the documentation (date) of first response (CR, VGPR, or PR) until the date of progression or last follow-up in the subset of patients who responded. Kaplan Meier method was used to compute this outcome.


Enrollment: 378
Study Start Date: November 2007
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Relapsed Myeloma (<4 Prior Regimens)

Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle

Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

Drug: dexamethasone
40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.
Drug: pomalidomide
2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
Other Name: CC-4047
Experimental: Lenalidomide Refractory Myeloma

Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle

Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

Drug: dexamethasone
40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.
Drug: pomalidomide
2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
Other Name: CC-4047
Experimental: Bortezomib/Lenalidomide Refractory/Relapsed Myeloma

Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle

Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

Drug: dexamethasone
40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.
Drug: pomalidomide
2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
Other Name: CC-4047
Experimental: Bortezomib/Lenalidomide Relapsed/Refractory Myeloma

Pomalidomide: 4 mg orally once daily, days 1-28 of 28 day cycle

Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

Drug: dexamethasone
40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.
Drug: pomalidomide
2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
Other Name: CC-4047
Experimental: Relapsed Myeloma (< 4 Prior Regimens)

Pomalidomide: 4 mg orally once daily, days 1-28 of 28 day cycle

Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

Drug: dexamethasone
40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.
Drug: pomalidomide
2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
Other Name: CC-4047
Experimental: Relapsed/Refractory Myeloma

Pomalidomide: 4 mg orally once daily, days 1-21 of 28 day cycle

Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

Drug: dexamethasone
40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.
Drug: pomalidomide
2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
Other Name: CC-4047
Experimental: Relapsed Amyloidosis

Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle

Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

Drug: dexamethasone
40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.
Drug: pomalidomide
2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
Other Name: CC-4047

Detailed Description:

OBJECTIVES:

  • To assess the response rate and duration of remission with low-dose CC-4047 plus dexamethasone in patients with relapsed or refractory multiple myeloma or amyloidosis.
  • To assess the toxicity of CC-4047 plus dexamethasone in this patient population.
  • To assess in an expansion cohort the response rate with an increase in CC-4047 dose among patients who fail to respond adequately to the initial starting dose following the first 2 courses of treatment.
  • To assess the response rate and duration of remission with CC-4047 plus dexamethasone in patients with lenalidomide resistant or refractory multiple myeloma.
  • To assess the response rate and duration of remission with CC-4047 plus dexamethasone in patients with previously treated light chain amyloidosis.
  • To assess the response rate and duration of remission with low- and high-dose CC-4047 plus dexamethasone in patients with lenalidomide and bortezomib refractory multiple myeloma.
  • To assess the response rate and duration of remission with high-dose CC-4047 plus dexamethasone in patients with relapsed or refractory myeloma who received ≤ 3 treatment regimens.

OUTLINE: Patients are grouped according to disease status (relapsed/refractory myeloma [closed to accrual as of 8/5/2008] vs lenalidomide resistant/refractory myeloma [closed to accrual as of 4/2/2009] vs previously treated light chain amyloidosis vs lenalidomide and bortezomib resistant/refractory myeloma {low-dose/day}[closed to accrual as of 11/20/09] vs lenalidomide and bortezomib resistant/refractory myeloma (high-dose/day) vs relapsed/refractory myeloma {high-dose/day}).

Patients receive oral CC-4047 on days 1-28 and oral dexamethasone on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 4 weeks and then at 6 months.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Symptomatic multiple myeloma
  • Previously treated disease meeting one of the following criteria:

    • Have light-chain amyloidosis that has been treated with at least one prior regimen
    • Symptomatic (relapsed or refractory) multiple myeloma

      • Patients must have received 1-3 treatment regimens
      • Induction therapy followed by autologous stem cell transplantation and consolidation considered one regimen
  • Measurable disease, as defined by 1 of the following:

    • Serum monoclonal protein ≥ 1.0 g by protein electrophoresis
    • More than 200 mg of monoclonal protein in the urine on 24-hour electrophoresis
    • Serum immunoglobulin free light chain (FLC) > 10 mg/dL and an abnormal FLC ratio
    • Measurable soft tissue plasmacytoma, not previously irradiated
    • More than 30% plasma cells in bone marrow
  • At least 10% plasma cells as measured by bone marrow aspirate, bone marrow biopsy, or labeling index
  • No monoclonal gammopathy of undetermined significance (not applicable for patients with amyloid)
  • No smoldering myeloma (not applicable for patients with amyloid)

PATIENT CHARACTERISTICS:

  • ECOG performance status 0, 1, or 2
  • ANC ≥ 1,000/μL
  • Platelet count ≥ 75,000/μL
  • Creatinine ≤ 2.5 mg/dL
  • Not pregnant or nursing

    • Women must refrain from breastfeeding during study participation and for at least 28 days after discontinuation of study drug
  • Negative pregnancy test
  • Fertile female patients must use two reliable forms of contraception simultaneously at least 28 days before beginning, during, and at least 28 days after completion of study drug

    • The two methods of reliable contraception must include one highly effective method (i.e., intrauterine device [IUD], hormonal [birth control pills, injections, or implants], tubal ligation, or partner's vasectomy) and one additional effective (barrier) method (i.e., latex condom, diaphragm, or cervical cap)
  • Fertile male patients must use a latex condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 28 days after stopping treatment
  • Men must agree to abstain from donating semen or sperm during study participation and for 28 days after discontinuation of study drug
  • Willing to abstain from donating blood during study participation and for 28 days after discontinuation of study drug
  • No uncontrolled infection
  • No other active malignancy
  • No New York Heart Association class III or IV cardiac disease (all patients)

    • Serum troponin T > 0.10 ng/mL (amyloid patients only)
  • No known positivity for HIV or active hepatitis infection
  • No active deep vein thrombosis or pulmonary embolism that has not been therapeutically anticoagulated
  • No condition, including the presence of laboratory abnormalities, that places the patient at unacceptable risk for participating in the study or confounds the ability to interpret data from the study
  • No known hypersensitivity to thalidomide or lenalidomide including development of erythema nodosum if characterized by a desquamating rash
  • No peripheral neuropathy > grade 2

PRIOR CONCURRENT THERAPY:

  • All previous cancer therapy, including chemotherapy and investigational agents, must have been discontinued ≥ 2 weeks prior to study registration
  • No radiotherapy ≤ 14 days prior to study registration
  • No other concurrent anti-myeloma therapy
  • No concurrent radiotherapy, except for palliation of a single painful bone lesion or fracture
  • Routine concurrent bisphosphonate therapy allowed for patients with myeloma bone disease
  • Willing and able to take aspirin or alternate prophylactic anticoagulation
  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: NCT00558896

Locations
United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259-5499
United States, Florida
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Martha Q. Lacy, MD Mayo Clinic
  More Information

Additional Information:
No publications provided by Mayo Clinic

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT00558896     History of Changes
Obsolete Identifiers: NCT01219634
Other Study ID Numbers: CDR0000574742, P30CA015083, 07-003064, NCI-2009-01283, MC0789
Study First Received: November 14, 2007
Results First Received: January 22, 2014
Last Updated: May 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
stage II multiple myeloma
stage III multiple myeloma
refractory multiple myeloma

Additional relevant MeSH terms:
Amyloidosis
Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Proteostasis Deficiencies
Metabolic Diseases
Neoplasms by Histologic Type
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
Pomalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2014