PCL-2 - Primary Plasma Cell Leukemia: a Prospective Phase Ii Study Incorporating Daratumumab to Chemotherapy and Stem Cell Transplantation (PCL-2 Study)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

2 Mar 2022 → ongoing

Decision date (initial)

2024-11-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515037-15-00

EudraCT number

2019-004170-26

ClinicalTrials.gov

NCT05054478

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To determine the best overall Response rate at completion of induction phase (very good partial response or better)

Secondary objectives 7

1. to evaluate progression-free survival
2. to assess overall hematological response rates
3. to evaluate overall survival
4. to assess safety and toxicity according to NCI CTCAE
5. to assess cytogenetic abnormalities of tumoral plasma cell
6. to analyze the prognostic value of minimal-residual disease (MRD) by sequencing (NGS), after completion of induction, before second consolidation, before Len consolidation and at the end of treatment.
7. to evaluate quality of life (EORTC QLQ-C30 domain scores)

Conditions and MedDRA coding

PRIMARY PLASMA CELL LEUKEMIA: A PROSPECTIVE PHASE II STUDY INCORPORATING DARATUMUMAB TO CHEMOTHERAPY AND STEM CELL TRANSPLANTATION

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Male or female patients 18 to 69 years old.
2. 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.)
3. 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.
4. Must be able to adhere to the study visit schedule and other protocol requirements
5. Patient with primary plasma cell leukemia disease as definedby the recent International Myeloma Working Group (IMWG2021): ≥ 5% circulating plasma cells in peripheral blood smears
6. 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
7. Eastern Cooperative Oncology Group (ECOG) performancestatus and/or other performance status 0, 1, or 2.
8. Eligible for high dose Melphalan therapy with ASCT
9. Total bilirubin ≤ 2 x the upper limit of the normal range (ULN).
10. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 X ULN.
11. Calculated creatinine clearance ≥ 20 mL/min (MDRD formulashould be used for calculating creatinine clearance values)
12. 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.)
13. Affiliated with an appropriate social security system.

Exclusion criteria 20

1. Male or female patients <18 or >69 years old
2. 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)
3. Prior history of symptomatic myeloma with 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 clairance 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 corticotherapy, 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
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 enrolment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the VGPR or better rate at the completion of induction phase (according to the IMWG response criteria)

Secondary endpoints 6

1. Progression-free Survival, Overall Survival, Time to progression and Duration of Response
2. overall hematological response rates
3. 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).
4. 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)
5. Minimal residual disease (MRD) assessed by NGS
6. Quality of life (EORTC QLQ-C30 domain scores)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr Bruno ROYER

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr Bruno ROYER

Locations

1 EU/EEA country · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications