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

NCT00558896 | Completed Phase 2 Results DMC

• 5 other identifiers: CDR0000574742P30CA01508307-003064NCI-2009-01283MC0789
• Study Type: interventional
• Target: 378
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

stage II multiple myeloma; stage III multiple myeloma; refractory multiple myeloma

Outcome Measures

Primary Outcomes (1)

• The Number of Confirmed Hematologic Responses (Complete, Partial, or Very Good Partial Response)

  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.

  Duration of study (up to 3 years)

Secondary Outcomes (2)

• Progression Free Survival (PFS)

  Duration of study (up to 5 years)

• Duration of Response

  Duration of study (up to 5 years)

Study Arms (7)

Relapsed Myeloma (<4 Prior Regimens)

EXPERIMENTAL

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; Drug: pomalidomide

Lenalidomide Refractory Myeloma

EXPERIMENTAL

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; Drug: pomalidomide

Bortezomib/Lenalidomide Refractory/Relapsed Myeloma

EXPERIMENTAL

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; Drug: pomalidomide

Bortezomib/Lenalidomide Relapsed/Refractory Myeloma

EXPERIMENTAL

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; Drug: pomalidomide

Relapsed Myeloma (< 4 Prior Regimens)

EXPERIMENTAL

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; Drug: pomalidomide

Relapsed/Refractory Myeloma

EXPERIMENTAL

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; Drug: pomalidomide

Relapsed Amyloidosis

EXPERIMENTAL

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; Drug: pomalidomide

Interventions

dexamethasone DRUG

40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.

Bortezomib/Lenalidomide Refractory/Relapsed Myeloma; Bortezomib/Lenalidomide Relapsed/Refractory Myeloma; Lenalidomide Refractory Myeloma; Relapsed Amyloidosis; Relapsed Myeloma (< 4 Prior Regimens); Relapsed Myeloma (<4 Prior Regimens); Relapsed/Refractory Myeloma

pomalidomide DRUG

2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).

Also known as: CC-4047

Bortezomib/Lenalidomide Refractory/Relapsed Myeloma; Bortezomib/Lenalidomide Relapsed/Refractory Myeloma; Lenalidomide Refractory Myeloma; Relapsed Amyloidosis; Relapsed Myeloma (< 4 Prior Regimens); Relapsed Myeloma (<4 Prior Regimens); Relapsed/Refractory Myeloma

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259-5499, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (2)

• Dispenzieri A, Buadi F, Laumann K, LaPlant B, Hayman SR, Kumar SK, Dingli D, Zeldenrust SR, Mikhael JR, Hall R, Rajkumar SV, Reeder C, Fonseca R, Bergsagel PL, Stewart AK, Roy V, Witzig TE, Lust JA, Russell SJ, Gertz MA, Lacy MQ. Activity of pomalidomide in patients with immunoglobulin light-chain amyloidosis. Blood. 2012 Jun 7;119(23):5397-404. doi: 10.1182/blood-2012-02-413161. Epub 2012 Apr 4.

  PMID: 22493299 DERIVED

• Lacy MQ, Allred JB, Gertz MA, Hayman SR, Short KD, Buadi F, Dispenzieri A, Kumar S, Greipp PR, Lust JA, Russell SJ, Dingli D, Zeldenrust S, Fonseca R, Bergsagel PL, Roy V, Stewart AK, Laumann K, Mandrekar SJ, Reeder C, Rajkumar SV, Mikhael JR. Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease. Blood. 2011 Sep 15;118(11):2970-5. doi: 10.1182/blood-2011-04-348896. Epub 2011 Jun 20.

  PMID: 21690557 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Dexamethasone; pomalidomide

Condition Hierarchy (Ancestors)

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)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Dr. Martha Lacy
• Organization: Mayo Clinic

lacy.martha@mayo.edu

Study Officials

• Martha Q. Lacy, MD

  Mayo Clinic

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2007
• First Posted: November 15, 2007
• Study Start: November 1, 2007
• Primary Completion: September 1, 2012
• Study Completion: October 25, 2017
• Last Updated: April 18, 2018
• Results First Posted: June 5, 2014

Record last verified: 2018-03

Locations

US (3)