Daratumumab, Thalidomide and Dexamethasone in Relapse and/or Refractory Myeloma

• Status: Recruiting
• Trial end date: 2022-07-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National University Hospital, Singapore
• Collaborators: International Myeloma Foundation; Janssen, LP
• Treatments: Antibodies, Monoclonal; BB 1101; Daratumumab; Dexamethasone; Dexamethasone acetate; Thalidomide

Criteria

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.