Primary Plasma Cell Leukemia: a Prospective Phase 2 Study Incorporating Daratumumab to Chemotherapy and Stem Cell Transplantation

NCT05054478 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: APHP1902052019-004170-26
• Study Type: interventional
• Target: 29
• Locations: 0 countries
• Sites: N/A

Brief Summary

Single-Arm phase 2 trial evaluating efficacy of incorporating Daratumumab to treatment of newly diagnosed primary plasma cell leukemia. Treatment will be based on Dara-VRd induction followed by first ASCT, Dara-VRd for first consolidation, second ASCT, Dara-VRd for 1 year as second consolidation and Lenalidomide for 1 year.

Conditions

Plasma Cell Leukemia

Outcome Measures

Primary Outcomes (1)

• VGPR or better at the completion of induction phase

  The VGPR or better rate (as determined by the reviewer) is defined as the proportion of patients with confirmed IMWG criteria for VGPR, CR or stringent CRrelative to the total number of patients in the ITT population

  completion of induction phase [4 Months]

Secondary Outcomes (20)

• Progression Free Survival

  3 years

• Response rates (sCR, CR, VGPR, PR, SD):

  after induction [4 months]

• Response rates (sCR, CR, VGPR, PR, SD):

  after ASCT n°2 [10 months]

• Response rates (sCR, CR, VGPR, PR, SD):

  after second consolidation phase [22 months]

• Response rates (sCR, CR, VGPR, PR, SD):

  end of treatment [34 months]

Study Arms (1)

Experimental Arm

EXPERIMENTAL

4 days of dexamethasone. According to local practice, one dose of doxorubicine (30 mg/m2 IV) or cyclophosphamide (750 mg/m2 IV) may also be added Induction Treatment (4 months): Subject will receive 4 x 28 days cycles of Dara-VRD induction: Daratumumab sc 1800 mg on D1 D8 D15 D22 for cycle1 \& 2 and D1 D15 for cycle 3 \& 4 Bortezomib sc 1.3 mg/m2 on D1 D4 D8 D11 for each cycle Lenalidomide po 25 mg on D1 to D21 for each cycle Dexamethasone po 20 mg on D1 D2 D8 D9 D15 D16 D22 D23 for each cycle High dose melphalan 200mg/m2 as conditioning therapy and first ASCT First consolidation : 2 cycles of Dara-VRd * Daratumumab 1800 mg s.c D1 D15 * Bortezomib 1.3 mg/m2 s.c D1 D8 D15 D22 * Lenalidomide 25 mg p.o from D1 to D21 * Dexa 20 mg p.o D1 D8 D15 D22 High dose melphalan 200mg/m2 as conditioning therapy and second ASCT Second consolidation : 6 cycles of Dara-VRd (every 2 months for 2 years) Then maintenance: Lenalidomide every 28 days (25 mg from D1 to D21) for 1 year

Drug: Daratumumab

Interventions

Daratumumab DRUG

Daratumumab added to induction, first consolidation and second consolidation

Experimental Arm

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients 18 to 69 years old.
• Patient with primary plasma cell leukemia disease as defined by the International Myeloma Working Group -IMWG (Annexe I)
• 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
• Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2.
• Eligible for high dose Melphalan therapy with ASCT
• Total bilirubin \<= 2 X the upper limit of the normal range (ULN).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<= 3 ULN.
• Calculated creatinine clearance \>= 20 mL/min
• 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.)
• 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.)

You may not qualify if:

• Male or female patients \<18 or \> 69 years old
• Prior history of malignancies, unless free of the disease for ≥ 5 years.
• Prior history of symptomatic myeloma; did not received any previous chemotherapy for myeloma except corticotherapy (dexamethasone 40 mg/d for 4 days max).
• Any other uncontrolled medical condition or comorbidity that might interfere with subject's participation.
• Pregnant or breast feeding females
• Known positive for HIV
• 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)
• 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.
• Patient with severe renal failure that require dialysis and clearance creatinine \< 20 ml/min
• 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.)
• Evidence of central nervous system (CNS) involvement
• Unable to take corticosteroid therapy, daratumumab, bortezomib and or lenalidomide at study entry.
• Ongoing active infection, especially ongoing pneumonitis
• 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
• Patients with a left ventricular ejection fraction under to 40 % (LVEF \<40%).

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

MeSH Terms

Conditions

Leukemia, Plasma Cell

Interventions

daratumumab

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Multiple Myeloma; Neoplasms, Plasma Cell; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Bruno Royer, MD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bruno Royer, MD

CONTACT

01 42 49 96 92; bruno.royer@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single-arm phase 2 trial

Study Record Dates

• First Submitted: July 31, 2021
• First Posted: September 23, 2021
• Study Start: October 1, 2021
• Primary Completion: June 1, 2024
• Study Completion (Estimated): February 1, 2028
• Last Updated: September 23, 2021

Record last verified: 2021-05