DARATUMUMAB for Primary plasma cell leukemia | Plasma cell leukemia

Inclusion criteria

• {"criterion_text":"- Male or female patients 18 to 69 years old."}
• {"criterion_text":"- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 X ULN."}
• {"criterion_text":"- Calculated creatinine clearance ≥ 20 mL/min (MDRD formulashould be used for calculating creatinine clearance values)"}
• {"criterion_text":"- Female patients who: -Have been postmenopausal for at least 2 years before thescreening visit, OR -Are surgically sterile, OR If they are of childbearingpotential, agree to practice 2 effective methods ofcontraception, at the same time, from the time of signing theinformed consent form through 90 days after the last doseof study drug, OR -Agree to practice true abstinence when this is in line withthe preferred and usual lifestyle of the subject. (Periodicabstinence [e.g., calendar, ovulation, symptothermal andpost-ovulation methods] and withdrawal are not acceptablemethods of contraception.)"}
• {"criterion_text":"- Affiliated with an appropriate social security system."}
• {"criterion_text":"- 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.)"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Must be able to adhere to the study visit schedule and other protocol requirements"}
• {"criterion_text":"- Patient with primary plasma cell leukemia disease as definedby the recent International Myeloma Working Group (IMWG2021): ≥ 5% circulating plasma cells in peripheral blood smears"}
• {"criterion_text":"- Voluntary written consent must be given before performance ofany study related procedure not part of standard medical care,with the understanding that consent may be withdrawn by thepatient at any time without prejudice to future medical care"}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performancestatus and/or other performance status 0, 1, or 2."}
• {"criterion_text":"- Eligible for high dose Melphalan therapy with ASCT"}
• {"criterion_text":"- Total bilirubin ≤ 2 x the upper limit of the normal range (ULN)."}

Exclusion criteria

• {"criterion_text":"- Male or female patients <18 or >69 years old"}
• {"criterion_text":"- 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.)"}
• {"criterion_text":"- Evidence of central nervous system (CNS) involvement"}
• {"criterion_text":"- Unable to take corticotherapy, daratumumab, bortezomib and or lenalidomide at study entry."}
• {"criterion_text":"- Ongoing active infection, especially ongoing pneumonitis"}
• {"criterion_text":"- Ongoing Cardiac dysfunction: specify e.g. uncontrolled hypertension, MI within 6 months, unstable Angina pectoris, Cardiac arrhythmia Grade 2 or higher"}
• {"criterion_text":"- Patients with a left ventricular ejection fraction under to 40 % (LVEF <40%)."}
• {"criterion_text":"- Use of any other experimental drug or therapy within 15 days of screening."}
• {"criterion_text":"- Any >grade 2 toxicity unresolved"}
• {"criterion_text":"- Inability or unwillingness to comply with birth control requirements"}
• {"criterion_text":"- Unable to take antithrombotic medicines at study entry"}
• {"criterion_text":"- History of malignancy within 3 years before the date of inclusion (exceptions are squamous and basal cell carcinomas of the skin, carcinoma of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion that in the opinion of the investigator, with concurrence with the coordinating Investigatior, is considered cured with minimal risk of recurrence within 3 years)"}
• {"criterion_text":"- Major surgery within 14 days before enrolment."}
• {"criterion_text":"- Prior history of symptomatic myeloma with previous chemotherapy for myeloma except corticotherapy (dexamethasone 40 mg/d for 4 days max)."}
• {"criterion_text":"- Any other uncontrolled medical condition or comorbidity that might interfere with subject’s participation."}
• {"criterion_text":"- Pregnant or breast feeding females"}
• {"criterion_text":"- Known positive for HIV"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Patient with severe renal failure that require dialysis and clairance creatinine < 20 ml/min"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint is the VGPR or better rate at the completion of induction phase (according to the IMWG response criteria)","definition_or_measurement_approach":"VGPR or better rate at completion of induction phase measured according to the International Myeloma Working Group (IMWG) response criteria."}

Secondary endpoints

• {"endpoint_text":"- Progression-free Survival, Overall Survival, Time to progression and Duration of Response","definition_or_measurement_approach":"Endpoints listed as Progression-free Survival, Overall Survival, Time to progression and Duration of Response (no further measurement detail provided in source)."}
• {"endpoint_text":"- overall hematological response rates","definition_or_measurement_approach":"Overall hematological response rates (no additional measurement details provided)."}
• {"endpoint_text":"- 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).","definition_or_measurement_approach":"Safety assessed using NCI Common Toxicity Criteria (CTCAE) v4; incidence of TEAE, SAE and laboratory abnormalities, changes in vital signs and physical exams."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Response evaluated stratified by specified chromosomal structural abnormalities (del(17p), t(4;14), t(11;14), t(14;16), t(14;20), amp(1q), del(1p))."}
• {"endpoint_text":"- Minimal residual disease (MRD) assessed by NGS","definition_or_measurement_approach":"MRD measured by next-generation sequencing (NGS)."}
• {"endpoint_text":"- Quality of life (EORTC QLQ-C30 domain scores)","definition_or_measurement_approach":"Quality of life measured using EORTC QLQ-C30 domain scores."}

France

Earliest CTIS Part Ii Submission Date

21-10-2024

Latest Decision Or Authorization Date

26-01-2026

Processing Time Days

462

Number Of Sites

16

Number Of Participants

29

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France