| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| PRIMARY PLASMA CELL LEUKEMIA |
|
| E.1.1.1 | Medical condition in easily understood language |
| PRIMARY PLASMA CELL LEUKEMIA |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10035223 |
| E.1.2 | Term | Plasma cell leukemia |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective is to determine the best overall Response rate at completion of induction phase (very good partial response or better) |
|
| E.2.2 | Secondary objectives of the trial |
The main secondary objective is to evaluate progression-free survival
The other secondary objectives are:
- to assess overall hematological response rates
- to evaluate overall survival
- to assess safety and toxicity according to NCI CTCAE
- to assess cytogenetic abnormalities of tumoral plasma cell
- to analyze the prognostic value of minimal-residual disease (MRD) by sequencing (NGS), after completion of induction, before second transplant, before second consolidation, before Len consolidation and at the end of treatment.
- to evaluate quality of life (EORTC QLQ-C30 domain scores) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or female patients 18 to 69 years old.
2. Patient with primary plasma cell leukemia disease as defined by the International Myeloma Working Group -IMWG (Annexe I)
3. Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care
4. Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2.
5. Eligible for high dose Melphalan therapy with ASCT
6. Total bilirubin <or= 2 x the upper limit of the normal range (ULN).
7. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <or= 3 x ULN.
8. Calculated creatinine clearance > or= 20 mL/min MDRD formula should be used for calculating creatinine clearance values
9. Female patients who:
- Have been postmenopausal for at least 2 years before the screening visit, OR
- are surgically sterile, OR If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR
- Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal and post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
10. Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following:
- Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
- Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal and post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
11. Patients agree
- not to share study medication with any other person and to return all unused study drugs to the investigator.
- to abstain from donating blood while taking the study drug therapy and for one week following discontinuation of the study drug therapy.
12. Must be able to adhere to the study visit schedule and other protocol requirements
13. Affiliated with an appropriate social security system |
|
| E.4 | Principal exclusion criteria |
1. Male or female patients <18 or > 69 years old
2. Prior history of malignancies, unless free of the disease for ≥ 5 years.
3. Prior history of symptomatic myeloma; did not received any previous chemotherapy for myeloma except corticotherapy (dexamethasone 40 mg/d for 4 days max).
4. Any other uncontrolled medical condition or comorbidity that might interfere with subject’s participation.
5. Pregnant or breast feeding females
6. Known positive for HIV
7. Known seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as a viremia at least 12 weeks after completion of antiviral therapy)
8. Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti- HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
9. Patient with severe renal failure that require dialysis and clearance creatinine < 20 ml/min
10. Prior local irradiation within two weeks before first dose. However, an exception (that is patients allowed to remain in the treatment phase of the study) is made for radiation therapy to a pathological fracture site to enhance bone healing or to treat post-fracture pain that is refractory to narcotic analgesics because pathologic bone fractures do not by themselves fulfil a criterion for disease progression.)
11. Evidence of central nervous system (CNS) involvement
12. Unable to take corticosteroid therapy, daratumumab, bortezomib and or lenalidomide at study entry.
13. Ongoing active infection, especially ongoing pneumonitis
14. Ongoing Cardiac dysfunction: specify e.g. uncontrolled hypertension, MI within 6 months, unstable Angina pectoris, Cardiac arrhythmia Grade 2 or higher, NYHA class III/IV
15. Patients with a left ventricular ejection fraction under to 40 % (LVEF <40%).
16. Use of any other experimental drug or therapy within 15 days of screening.
17. Any >grade 2 toxicity unresolved
18. Inability or unwillingness to comply with birth control requirements
19. Unable to take antithrombotic medicines at study entry
20. Major surgery within 14 days before enrollment
21. Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol.
22. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
23. Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of daratumumab and lenalidomide including difficulty swallowing. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is the VGPR or better rate at the completion of induction phase (according to the IMWG response criteria) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| At the completion of induction phase |
|
| E.5.2 | Secondary end point(s) |
- Progression-free Survival, Overall Survival, Time to progression and Duration of Response.
- overall hematological response rates
- Assess safety by type, frequency, severity, relationship of adverse events to study treatment and changes in vital signs, physical exams. Incidence of Treatment Emergent Adverse Event (TEAE), Serious Adverse Event (SAE) and laboratory abnormalities using National Cancer Institute (NCI) common toxicity criteria (CCTAE V4).
- Evaluate response according to chromosomal structural abnormalities such as del(17p), t(4;14), t(11;14), t(14;16), t(14;20), amp(1q) and del(1p).
- Minimal residual disease (MRD) assessed by NGS
- Quality of life (EORTC QLQ-C30 domain scores) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | No |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 16 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
Print
