Study of DTP3 in patients with relapsed or refractory multiple myeloma or diffuse large B-cell lymphoma
- Conditions
- Multiple myeloma and diffuse large B cell lymphomaCancerMultiple myeloma, Diffuse large B-cell lymphoma
- Registration Number
- ISRCTN13777452
- Lead Sponsor
- Imperial College London
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 72
Disease-specific inclusion criteria (MM):
1. Documented diagnosis of multiple myeloma (IMWG 2014 criteria)
2. Any R-ISS stage
3. Measurable disease as determined by at least one of:
3.1. Serum M-protein =500 mg/dL
3.2. Urine M-protein =200 mg/24 hour
3.3. Involved serum free light chain (sFLC) level =10 mg/dL, provided that serum sFLC ratio is abnormal
4. Has previously been treated with an ImiD, a proteasome inhibitor and an anti-CD38 antibody
5. Previous treatment with at least two prior regimens
6. Relapsed (after most recent regimen) or refractory disease [refractory defined as either best response of progression on previous regimen or progression within 6 months of achieving PR (or better) on previous regimen]
7. Requires active therapeutic intervention (in the judgement of the investigator)
8. Not currently a candidate for stem cell transplantation or CAR T-cell therapy
Disease-specific inclusion criteria [DLBCL]:
9. Documented diagnosis of DLBCL [WHO 2016 criteria]
9.1. Diffuse large B-cell lymphoma – de novo or transformed (from follicular lymphoma only)
9.2. High-grade B-cell lymphoma (MYC with BCL2 and/or BCL6); High-grade B-cell lymphoma (NOS)
9.3. Primary mediastinal B-cell lymphoma
10. Non-GCB by local IHC [Dose Expansion Only]
11. Measurable disease as determined by CT (or MRI) documentation of two or more clearly demarcated lesions/nodes with a long axis >1.5 cm and short axis >1.0 cm or one clearly demarcated lesion/node with a long axis >2.0 cm and short-axis =1.0 cm AND baseline FDG-PET scans must demonstrate positive lesion compatibility with CT (or MRI) defined anatomical tumour sites
12. No available standard of care therapeutic regimens in the opinion of the investigator
13. Relapsed (after most recent regimen) or refractory disease [refractory defined as either best response of progression on previous regimen or progression within 6 months of achieving PR (or better) on previous regimen]
14. Requires active therapeutic intervention (in the judgement of the investigator)
15. Not currently a candidate for stem cell transplantation or CAR T-cell therapy
General inclusion criteria:
16. Adequate hematologic function:
16.1. ANC = 1 x 10e9/l (no restriction on prior growth factor support)
16.2. Platelet count =50 x 10e9/l (no platelet transfusions permitted in 7 last days prior to assessment). Platelet counts of <50 x 10e9/l may be considered, on a case by case basis, for patients with significant malignant bone marrow involvement, after discussion with the medical monitor
16.3. Hb =8 g/dl (no RBC transfusions permitted in 7 last days prior to assessment)
16.4. aPTT and PT within institutional normal range (unless the patient is on full-dose warfarin, in which case INR within normal institutional therapeutic range is acceptable)
17. No evidence of bleeding diathesis or coagulopathy
18. Adequate laboratory biochemical function:
18.1. Serum creatinine =1.5 x ULN OR creatinine clearance =30 ml/min (Cockcroft-Gault calculation)
18.2. Bilirubin level <1.5 X ULN
18.3. AST and ALT <2.5 X ULN
19. ECOG performance status 0-2
20. Age >16 years
21. Written informed consent prior to admission into the study
1. Primary or secondary CNS lymphoma
2. T-cell rich B-cell lymphoma
3. Plasma cell leukaemia
4. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
5. Primary amyloidosis
6. Clinically significant (in the opinion of the investigator) cardiovascular disease, such as:
• History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty/stenting/bypass grafting within the past 6 months prior to the date of consent
• Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system
• Severe cardiac arrhythmia requiring medication or severe conduction abnormalities
• Poorly controlled hypertension (resting diastolic blood pressure >100 mmHg)
• Clinically significant valvular disease, cardiomegaly, ventricular hypertrophy, or cardiomyopathy, QTc prolongation [defined as a QTc interval >450 msec (males) or >470 msec (females)] or other significant ECG abnormalities including 2nd degree (type II) or 3rd degree AV block or bradycardia (ventricular rate <50 beats/min)
7. Clinically significant (in the opinion of the investigator) cerebrovascular disorders or vascular dementia
8. Clinically significant (in the opinion of the investigator) intercurrent medical or psychiatric illness, including serious active infection
9. Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain)
10. Concurrent treatment with other experimental drugs
11. A daily requirement for prednisone at a dose of >10 mg/day (or steroid equivalent) at time of starting the first dose of study drug. Higher doses are permitted for primary disease symptomatic control during the screening period, after discussion with the medical monitor, but this must have been tapered to a dose of =10 mg/day by the time treatment with DTP3 starts
12. Sem cell transplant (autologous/allogeneic) or CAR T-cell regimen within 12 weeks of the date of consent
13. Participation in another clinical trial with any investigational drug within 28 days prior to the date of consent
14. Prior (non-experimental) MM or DLBCL therapy within 28 days of the date of consent. Concomitant bisphosphonate therapy is permitted
15. Prior radiotherapy within 28 days of the date of consent. Localised palliative radiation therapy to a single site for symptomatic control is acceptable within this period
16. Anticipated need for concurrent radiotherapy during the study
17. Past or current history of other neoplasms, except for:
17.1. Curatively treated non-melanoma skin cancer
17.2. Adequately treated in situ carcinoma of the cervix
17.3. Prostate adenocarcinoma with documented PSA value of <0.1 ng/ml within 6 weeks of the date of consent
17.4. Other cancer curatively treated and with no evidence of disease for at least 3 years before the date of consent.
18. Known HIV infection
19. Active hepatitis C virus (HCV) or hepatitis B virus (HBV). Patients who are positive for hepatitis B core antibody, hepatitis B surface antigen or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result
20. Ability to become pregnant (or already pregnant or lactating). However, those female patients who have a negative serum or urine pregnancy test before enrolment and agree to use two highly effective forms of contraception:
20.1. Oral, injected or implanted hormonal contraception and condom
20.2. Have an intra-uterine device and condom
20.3. Vasectomised partner
20.4. Sexual abstine
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method