Pomalidomide-Cyclophosphamide-Dexamethasone (PCD) Versus Pomalidomide-Dexamethasone (PD) in Relapse or Refractory Myeloma
NCT ID: NCT03143049
Last Updated: 2017-11-06
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE3
120 participants
INTERVENTIONAL
2017-09-13
2022-06-01
Brief Summary
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Detailed Description
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Pomalidomide is a new immunomodulatory drug, which has been shown to be active in myeloma patients who relapse after bortezomib and lenalidomide. A recent phase III study comparing pomalidomide plus dexamethasone with placebo plus high dose dexamethasone in patients with prior exposure to bortezomib and lenalidomide, showed that the use of pomalidomide significantly improve the overall survival of these patients. In an Asian study, it appears that the addition of cyclophosphamide can induce further response in patients without a response to PD. 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. Our hypothesis is therefore that PCD will be better than PD and should be the standard pomalidomide containing regimen for relapse myeloma patients. This combination will also be highly relevant to Asian patients because cyclophosphamide is a relatively cheap drug and the combination will be cost effective if proven to be better than PD.
Rationale for the Study Purpose There is a relative lack of data on the efficacy and tolerability of PCD in Asian Patients. The current study will also allow us to test if PCD is better than PD in the treatment of relapse myeloma patients.
Rationale for Study Population The study population will be myeloma patients who have relapsed following prior treatment with bortezomib and lenalidomide. Pomalidomide is the current approved treatment choice for this group of patients and a common indication for us in Asia.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
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.
TREATMENT
NONE
Study Groups
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Pomalidomide, Cyclophosphamide, Dex (PCD)
PCD
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, Dex (PD)
PD
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).
Interventions
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PCD
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).
PD
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).
Eligibility Criteria
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Inclusion Criteria
2. Patients must have evaluable multiple myeloma with at least one of the following (within 21 days of starting treatment)
1. Serum M-protein ≥ 0.5g/dL, or
2. 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
3. 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)
4. 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
5. Males and females ≥ 18 years of age or \> country's legal age for adult consent
6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
7. Patients must meet the following clinical laboratory criteria with 21 days of starting treatment:
1. Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet ≥ 50,000/mm3 (≥ 30,000/mm3 if myeloma involvement in the bone marrow is \>50%)
2. Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN.
3. Calculated creatinine clearance ≥ 30mL/min or creatinine \< 3mg/dL.
8. Female patients who:
1. Are naturally postmenopausal for at least 2 year before enrolment
2. Are surgically sterile
3. If they are of childbearing potential\*\*, agree to
* adhere to the pomalidomide pregnancy prevention risk management program in Appendix 8 :
* All women of childbearing potential must agree to have two negative pregnancy test within 10-14 days and 24hrs before commencing pomalidomide and use two reliable methods of contraception simultaneously or practice complete abstinence from any heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting study; 2) while participating in the study; 3) dose interruptions; and 4) for at least 28 days after study treatment discontinuation. The two methods of reliable contraception must include one highly effective method and one additional effective method to prevent pregnancy, not plan on conceiving children during or within 6 months following pomalidomide. (See Appendix 8 Pregnancy Prevention and Risk Management Program)
9. Male patients, even if surgically sterilized (i.e. status post-vasectomy), who:
1. Agree to practice effective barrier contraception during the entire study treatment period and through 28 days after the last dose of study treatment, OR
2. Agree to completely abstain from heterosexual intercourse, AND
3. Must also adhere to the guidelines of the pomalidomide pregnancy prevention and risk management program
10. Written informed consent in accordance with federal, local and institutional guidelines
* A female of childbearing potential (FCBP) is defined as a sexually mature woman who: 1 has not undergone a hysterectomy or bilateral oophorectomy or 2, has not been naturally post-menopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (I.E, has had menses at any time in the preceding 24 consecutive months).
Exclusion Criteria
2. Multiple Myeloma of IgM subtype
3. Glucocorticoid therapy (prednisolone \> 30mg/day or equivalent) within 14 days prior to informed consent obtained
4. POEMS syndrome
5. Plasma cell leukemia or circulating plasma cells ≥ 2 x 109/L
6. Waldenstrom's Macroglobulinaemia
7. Patients with known amyloidosis
8. Chemotherapy with approved or investigation anticancer therapeutics within 21 days prior to starting pomalidomide treatment
9. 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
10. Immunotherapy (excluding steroids) 21 days prior to start of pomalidomide
11. Major surgery (excluding kyphoplasty) within 28 days prior to start of pomalidomide
12. 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
13. 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)
14. Patients with known cirrhosis
15. Second malignancy within the past 3 years except:
1. Adequately treated basal cell or squamous cell skin cancer
2. Carcinoma in situ of the cervix
3. Breast carcinoma in situ with full surgical resection
16. Patients with myelodysplastic syndrome
17. Patients with steroid or lenalidomide hypersensitivity
18. Prior treatment with pomalidomide
19. Ongoing graft-versus-host disease
20. Patients with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to starting pomalidomide treatment
21. Contraindication to any of the required concomitant drugs or supportive treatments
22. Any clinically significant medical disease or psychiatric condition that, in the investigator's opinion, may interfere with protocol adherence or a patient's ability to give informed consent.
21 Years
99 Years
ALL
No
Sponsors
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Celgene
INDUSTRY
International Myeloma Foundation
OTHER
National University Hospital, Singapore
OTHER
Responsible Party
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Principal Investigators
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Wee Joo Chng
Role: PRINCIPAL_INVESTIGATOR
National University Hospital, Singapore
Locations
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Queen Mary Hospital
Hong Kong, , Hong Kong
Japan, , Japan
National University Hospital
Singapore, , Singapore
South Korea, , South Korea
National Taiwan University
Taipei, , Taiwan
Countries
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Central Contacts
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References
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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.
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.
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.
Other Identifiers
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AMN003
Identifier Type: -
Identifier Source: org_study_id