Pomalidomide-Cyclophosphamide-Dexamethasone (PCD) Versus Pomalidomide-Dexamethasone (PD) in Relapse or Refractory Myeloma

NCT03143049 | Unknown Phase 3

• 1 other identifier: AMN003
• Study Type: interventional
• Target: 120
• Locations: 5 countries
• Sites: 5

Brief Summary

Myeloma patients who relapse after prior treatment with bortezomib and lenalidomide have survival of less than 1 year. Recently, a randomized study of Pomalidomide and dexamethasone conducted in compared with placebo and dexamethasone showed that pomalidomide can improve survival of this group of patients. As a result, pomalidomide is now approved by the FDA and EMA for use in patients with relapsed/refractory myeloma previously treated with bortezomib and lenalidomide. We have conducted a study using Pomalidomide plus Dexamethasone (PD) in Asian patients, which showed good efficacy and safety profile. More important for patients with suboptimal response to PD will achieve a clinically meaningful response with the addition of oral cyclophosphamide (PCD). In the United States, a small randomised phase 2 study of PCD versus PD showed that PCD have a higher response rates, produce deeper response and correspondingly longer progression free survival. There is till date no randomised phase 3 study between these regimens. This will be important to determine what is the best combination including pomalidomide for use in relapse myeloma.

Conditions

Relapse Multiple Myeloma

Keywords

Pomalidomide

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  Defined as the time from commencement of treatment with either PCD or PD to disease progression or death due to any cause, whichever occurs first.

  Assessed up to 100 months

Secondary Outcomes (4)

• Overall response rate (ORR)

  Assessed up to 100 months

• Overall survival (OS)

  An average of 5 years

• Duration of response (DOR)

  Assessed up to 100 months

• Number of Participants affected by Adverse Events

  From the time of enrolment into study till 3 years from the date of the last patient randomized

Study Arms (2)

Pomalidomide, Cyclophosphamide, Dex (PCD)

EXPERIMENTAL

Drug: PCD

Pomalidomide, Dex (PD)

ACTIVE COMPARATOR

Drug: PD

Interventions

PCD DRUG

For PCD, patients will be treated as follows: PO pomalidomide 4mg from D1-21, PO cyclophosphamide 400mg on D1, 8 and 15, and PO or IV dexamethasone 40mg D1, 8, 15 and 22 in a 28-day cycle. Patients will be assessed every 28 days (+/- 10 days). Patients shall receive the treatment until disease progression, unacceptable toxicity as determined by treating physician, withdrawal of consent or mortality (whichever occurs first).

Pomalidomide, Cyclophosphamide, Dex (PCD)

PD DRUG

For PD, Patients will be treated as follows: PO pomalidomide 4mg from D1-21 and PO or IV dexamethasone 40mg D1, 8, 15 and 22 in a 28-day cycle. Patients will be assessed every 28 days (+/- 10 days). Patients shall receive the treatment until disease progression, unacceptable toxicity as determined by treating physician, withdrawal of consent or mortality (whichever occurs first).

Pomalidomide, Dex (PD)

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Multiple myeloma, diagnosed according to standard criteria, with relapsing and refractory disease at study entry
• Patients must have evaluable multiple myeloma with at least one of the following (within 21 days of starting treatment)
• Serum M-protein ≥ 0.5g/dL, or
• In subjects without detectable serum M-protein, Urine M-protein ≥ 200mg/24 hour, or serum free light chai (sFLC) \> 100mg/L (involved light chain) and an abnormal kappa/Lambda ratio
• Can receive up to 6 lines of prior treatment. (Induction therapy followed by stem cell transplantation and consolidation/maintenance therapy will be considered as one line of treatment)
• Must be relapse refractory to prior lenalidomide and bortezomib. Refractoriness is defined as disease progression on treatment or progression within 6 months after the last dose of a given therapy. Relapse is defined according to the criteria of IMWG
• Males and females ≥ 18 years of age or \> country's legal age for adult consent
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
• Patients must meet the following clinical laboratory criteria with 21 days of starting treatment:
• Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet ≥ 50,000/mm3 (≥ 30,000/mm3 if myeloma involvement in the bone marrow is \>50%)
• Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN.
• Calculated creatinine clearance ≥ 30mL/min or creatinine \< 3mg/dL.
• Female patients who:
• Are naturally postmenopausal for at least 2 year before enrolment
• Are surgically sterile

You may not qualify if:

• Female patients who are lactating or pregnant
• Multiple Myeloma of IgM subtype
• Glucocorticoid therapy (prednisolone \> 30mg/day or equivalent) within 14 days prior to informed consent obtained
• POEMS syndrome
• Plasma cell leukemia or circulating plasma cells ≥ 2 x 109/L
• Waldenstrom's Macroglobulinaemia
• Patients with known amyloidosis
• Chemotherapy with approved or investigation anticancer therapeutics within 21 days prior to starting pomalidomide treatment
• Focal radiation therapy within 7 days prior to start of pomalidomide. Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to start of pomalidomide
• Immunotherapy (excluding steroids) 21 days prior to start of pomalidomide
• Major surgery (excluding kyphoplasty) within 28 days prior to start of pomalidomide
• Active congestive heart failure (New York Heart Association \[NYHA\] Class III or IV), symptomatic ischaemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within 4 months prior to informed consent obtained
• Known HIV seropositive, hepatitis C infection, and/or hepatitis B (except for patients with hepatitis B surface antigen or core antibody receiving and responding to antiviral therapy directed at hepatitis B: these patients are allowed)
• Patients with known cirrhosis
• Second malignancy within the past 3 years except:

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• Celgene: collaborator
• International Myeloma Foundation: collaborator

Study Sites (5)

Queen Mary Hospital

Hong Kong, Hong Kong

NOT YET RECRUITING

Unknown Facility

Japan, Japan

NOT YET RECRUITING

National University Hospital

Singapore, Singapore

RECRUITING

Unknown Facility

South Korea, South Korea

NOT YET RECRUITING

National Taiwan University

Taipei, Taiwan

NOT YET RECRUITING

Related Publications (3)

• Miguel JS, Weisel K, Moreau P, Lacy M, Song K, Delforge M, Karlin L, Goldschmidt H, Banos A, Oriol A, Alegre A, Chen C, Cavo M, Garderet L, Ivanova V, Martinez-Lopez J, Belch A, Palumbo A, Schey S, Sonneveld P, Yu X, Sternas L, Jacques C, Zaki M, Dimopoulos M. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013 Oct;14(11):1055-1066. doi: 10.1016/S1470-2045(13)70380-2. Epub 2013 Sep 3.

  PMID: 24007748 BACKGROUND

• Larocca A, Montefusco V, Bringhen S, Rossi D, Crippa C, Mina R, Galli M, Marcatti M, La Verde G, Giuliani N, Magarotto V, Guglielmelli T, Rota-Scalabrini D, Omede P, Santagostino A, Baldi I, Carella AM, Boccadoro M, Corradini P, Palumbo A. Pomalidomide, cyclophosphamide, and prednisone for relapsed/refractory multiple myeloma: a multicenter phase 1/2 open-label study. Blood. 2013 Oct 17;122(16):2799-806. doi: 10.1182/blood-2013-03-488676. Epub 2013 Aug 16.

  PMID: 23954889 BACKGROUND

• Kim JS, Song Y, Jen WY, Chim CS, Lee JJ, Yoon SS, Ng SC, Gan GG, Handa H, Lee JH, Kim K, Ito S, Huang JS, Min CK, Ooi Gaik Ming M, de Mel S, Soekojo C, Li X, Awasthi N, Pokharkar Y, Durie BG, Chng WJ. Randomized Phase 3 study of pomalidomide cyclophosphamide dexamethasone versus pomalidomide dexamethasone in relapse or refractory myeloma: an Asian Myeloma Network study (AMN003). Blood Cancer J. 2025 Oct 6;15(1):155. doi: 10.1038/s41408-025-01356-z.

  PMID: 41052983 DERIVED

Study Officials

• Wee Joo Chng

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wee Joo Chng

CONTACT

6779 5555; mdccwj@nus.edu.sg

Adeline Lin

CONTACT

adeline_hf_lin@nuhs.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a randomised phase 3 study in Asian patients with relapse multiple myeloma after prior bortezomib and lenalidomide who will be treated by PD or PCD. Randomisation will be 1:1 using a computer algorithm. There will be no blinding. The patient in the 2 arms will be stratified according to ISS stage 1 or 2 versus stage 3. Cross-over for patients randomised to Pomalidomide and Dexamethasone at progression: Upon progression, patients randomized to pomalidomide and dexamethasone (PD) can cross-over to the PCD arm and have cyclophosphamide added to their regimen according to the PCD regimen. Cyclophosphamide should be added at the beginning of a cycle. They can continue on PCD until further progression. However for these PD patients that cross-over to PCD, the primary endpoint for analysis will be based on response and progression on PD.

Study Record Dates

• First Submitted: April 13, 2017
• First Posted: May 8, 2017
• Study Start: September 13, 2017
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2022
• Last Updated: November 6, 2017

Record last verified: 2017-03

Locations

SG (1); TW (1); JP (1); KR (1); HK (1)