Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03143049
Recruitment Status : Recruiting
First Posted : May 8, 2017
Last Update Posted : November 6, 2017
Sponsor:
Collaborators:
Celgene
International Myeloma Foundation
Information provided by (Responsible Party):
National University Hospital, Singapore

Tracking Information
First Submitted Date  ICMJE April 13, 2017
First Posted Date  ICMJE May 8, 2017
Last Update Posted Date November 6, 2017
Actual Study Start Date  ICMJE September 13, 2017
Estimated Primary Completion Date June 1, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 3, 2017)
Progression free survival (PFS) [ Time Frame: Assessed up to 100 months ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 3, 2017)
  • Overall response rate (ORR) [ Time Frame: Assessed up to 100 months ]
    Defined as the percentage of patients enrolled that achieve a complete response (CR), or stringent complete response (sCR), or very good partial response (VGPR), or partial response (PR) based on the International Myeloma Working Group criteria anytime from commencement of treatment to the end of study.
  • Overall survival (OS) [ Time Frame: An average of 5 years ]
    Defined as the time from commencement of treatment to the date of death
  • Duration of response (DOR) [ Time Frame: Assessed up to 100 months ]
    Defined as the time from first evidence of PR or VGPR, or CR, or sCR to confirmation of disease progression or death due to any cause.
  • Number of Participants affected by Adverse Events [ Time Frame: From the time of enrolment into study till 3 years from the date of the last patient randomized ]
    Assessed on the basis of the frequency and severity of adverse events
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pomalidomide-Cyclophosphamide-Dexamethasone (PCD) Versus Pomalidomide-Dexamethasone (PD) in Relapse or Refractory Myeloma
Official Title  ICMJE Randomized Phase 3 Study of Pomalidomide-Cyclophosphamide-Dexamethasone (PCD) Versus Pomalidomide-Dexamethasone (PD) in Relapse or Refractory Myeloma. An AMN Study
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.
Detailed Description

In this study, we will prospectively enrol 120 Asian patients with relapsed myeloma after prior treatment with bortezomib and lenalidomide, and randomised them between PCD and PD (60 in each arms). Centers in Singapore, Korea, Taiwan, and Hong Kong will participate in this study.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

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.

Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Relapse Multiple Myeloma
Intervention  ICMJE
  • Drug: 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).

  • Drug: 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).

Study Arms  ICMJE
  • Experimental: Pomalidomide, Cyclophosphamide, Dex (PCD)
    Intervention: Drug: PCD
  • Active Comparator: Pomalidomide, Dex (PD)
    Intervention: Drug: PD
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 3, 2017)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 1, 2022
Estimated Primary Completion Date June 1, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Multiple myeloma, diagnosed according to standard criteria, with relapsing and refractory disease at study entry
  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:

  1. Female patients who are lactating or pregnant
  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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Wee Joo Chng 6779 5555 mdccwj@nus.edu.sg
Contact: Adeline Lin adeline_hf_lin@nuhs.edu.sg
Listed Location Countries  ICMJE Japan,   Hong Kong,   Korea, Republic of,   Singapore,   Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03143049
Other Study ID Numbers  ICMJE AMN003
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National University Hospital, Singapore
Study Sponsor  ICMJE National University Hospital, Singapore
Collaborators  ICMJE
  • Celgene
  • International Myeloma Foundation
Investigators  ICMJE
Principal Investigator: Wee Joo Chng National University Hospital, Singapore
PRS Account National University Hospital, Singapore
Verification Date March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP