Relapse and / or Refractory Myeloma Clinical Trial
Official title:
Phase 2 Study of Daratumumab in Combination With Thalidomide and Dexamethasone in Relapse and / or Refractory Myeloma
| NCT number | NCT03143036 |
| Other study ID # | AMN004 |
| Secondary ID | |
| Status | Recruiting |
| Phase | Phase 2 |
| First received | |
| Last updated | |
| Start date | May 1, 2018 |
| Est. completion date | July 1, 2022 |
Myeloma patients who relapse after prior treatment with bortezomib and lenalidomide have
survival of less than 1 year. A number of new drugs have been approved for the treatment of
relapse myeloma in the last couple of years, including, Elotuzumab, Panobinostat, Ixazomib,
carfilzomib and Pomalidomide. However, most of these drugs either do not have good single
agent activity or still belongs to the category of immunomodulatory drugs or proteasome
inhibitors. Daratumumab is a monoclonal antibody against CD38 that is highly expressed on
myeloma plasma cells. In phase ½ studies, it has impressive single agent activity in relapse
and refractory myeloma with a very acceptable toxicity profile. This set the stage for
combinations with daratumumab to increase efficacy and improve outcome of patients with
myeloma. The use of immunomodulatory drugs, such as thalidomide and lenalidomide, has been
shown to augment NK cell activity. NK cells are important mediator of antibody dependent
cellular cytotoxicity. We therefore hypothesize that the combination of Daratumumab with
thalidomide may therefore improve the efficacy of the treatment.
In this study, we will plan to perform a phase II trial using the Daratumumab, Thalidomide,
Dexamethasone combination in 100 myeloma patients with relapse myeloma in Asia.
| Status | Recruiting |
| Enrollment | 100 |
| Est. completion date | July 1, 2022 |
| Est. primary completion date | July 1, 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 21 Years to 99 Years |
| Eligibility |
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. Must receive at least 1 line of prior treatment. (Induction therapy followed by stem cell transplantation and consolidation/maintenance therapy will be considered as one line of treatment) 4. Must have relapsed disease and/or be refractory to prior treatment except for thalidomide or lenalidomide. 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. 8. Written informed consent in accordance with federal, local and institutional guidelines 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. Existing peripheral neuropathy of grade 2 or higher or presence of neuropathic pain 8. Patients with known amyloidosis 9. Chemotherapy with approved or investigation anticancer therapeutics within 21 days prior to starting Dara-TD treatment 10. Focal radiation therapy within 7 days prior to start of Dara-TD. Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to start of pomalidomide 11. Immunotherapy (excluding steroids) 21 days prior to start of Dara-TD 12. Major surgery (excluding kyphoplasty) within 28 days prior to start of Dara-TD 13. 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 14. 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) 15. Patients with known cirrhosis 16. Patients with creatinine clearance <30m/min 17. 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 18. Patients with myelodysplastic syndrome 19. Patients with steroid or thalidomide hypersensitivity 20. Patients previously treated with daratumumab or other anti-CD38 antibodies. 21. Ongoing graft-versus-host disease 22. Patients with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to starting Dara-TD treatment 23. Disease refractory to thalidomide or lenalidomide 24. Contraindication to any of the required concomitant drugs or supportive treatments 25. 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. |
| Country | Name | City | State |
|---|---|---|---|
| Hong Kong | Queen Mary Hospital | Hong Kong | |
| Korea, Republic of | Samsung Medical Center | South Korea | |
| Singapore | National University Hospital | Singapore | |
| Singapore | Singapore General Hospital | Singapore | |
| Taiwan | National Taiwan University | Taipei |
| Lead Sponsor | Collaborator |
|---|---|
| National University Hospital, Singapore | International Myeloma Foundation, Janssen, LP |
Hong Kong, Korea, Republic of, Singapore, Taiwan,
3. Palumbo A, Chanan-Khan A, Weisel K, et al. Phase III randomized controlled study of daratumumab, bortezomib and dexamethasone (DVd) versus bortezomib and dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma (RRMM): CASTOR study. J Clin Oncol 2016; 34 (Suppl abstr LBA4)
4. Dimopoulos MA, Oriol A, Nahi H, et al. An open-label, randomised phase 3 study of daratumumab, lenalidomide, dexamethasone (DRD) versus lenalidomide and dexamethasone (RD) in relapsed or refractory multiple myeloma (RRMM): POLLUX. EHA 2016 Abstract LB2238
Lokhorst HM, Plesner T, Laubach JP, Nahi H, Gimsing P, Hansson M, Minnema MC, Lassen U, Krejcik J, Palumbo A, van de Donk NW, Ahmadi T, Khan I, Uhlar CM, Wang J, Sasser AK, Losic N, Lisby S, Basse L, Brun N, Richardson PG. Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma. N Engl J Med. 2015 Sep 24;373(13):1207-19. doi: 10.1056/NEJMoa1506348. Epub 2015 Aug 26. — View Citation
Lonial S, Weiss BM, Usmani SZ, Singhal S, Chari A, Bahlis NJ, Belch A, Krishnan A, Vescio RA, Mateos MV, Mazumder A, Orlowski RZ, Sutherland HJ, Bladé J, Scott EC, Oriol A, Berdeja J, Gharibo M, Stevens DA, LeBlanc R, Sebag M, Callander N, Jakubowiak A, White D, de la Rubia J, Richardson PG, Lisby S, Feng H, Uhlar CM, Khan I, Ahmadi T, Voorhees PM. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet. 2016 Apr 9;387(10027):1551-60. doi: 10.1016/S0140-6736(15)01120-4. Epub 2016 Jan 7. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Progression free survival (PFS) | To assess the progression free survival (PFS) for daratumumab in combination with thalidomide and dexamethasone in Asian patients with relapsed myeloma. | Time from commencement of treatment to disease progression or death, whichever occurs first, assessed up to 100 months | |
| Secondary | Overall Response Rate (ORR) | 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 with daratumumab, thalidomide and dexamethasone to the end of studyaseline until disease progression, unmanageable adverse event or death, whichever occurs first, approximately up to 3 years | |
| Secondary | Overall survival (OS) | Time from commencement of treatment with daratumumab, thalidomide and dexamethasone to the date of death. | Up to approximately 5 years (anticipated) after the last participant is enrolled | |
| Secondary | Duration of response (DOR) | the time from first evidence of PR or VGPR, or CR, or sCR to confirmation of disease progression or death due to any cause. | the time from first evidence of PR or VGPR, or CR, or sCR to confirmation of disease progression or death due to any cause, assessed up to 100 months | |
| Secondary | Number of Participants affected by Adverse Events | assessed on the basis of the frequency and severity of adverse events | from the time of enrolment into study till 3 years from the date of the last patient randomized |