DVRd in the Treatment of Patients With Newly Diagnosed Double-hit Multiple Myeloma

NCT06158269 | Recruiting Phase 2

• 1 other identifier: MMY2094
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Evaluate the efficacy of DVRd in patients with newly diagnosed double-hit multiple myeloma (MM) and the feasibility of minimal residual disease (MRD) guided maintenance therapy

Conditions

Multiple Myeloma

Keywords

double-hit; daratumumab; bortezomib; lenalidomide; minimal residual disease; tailored maintenance therapy

Outcome Measures

Primary Outcomes (1)

• MRD negative rate

  MRD detected by next generation sequencing

  through study completion, an average of 3 year

Secondary Outcomes (7)

• Duration of negative MRD

  through study completion, an average of 3 year

• stringent complete response (sCR)

  through study completion, an average of 3 year

• ORR

  through study completion, an average of 3 year

• Duration of response (DOR)

  through study completion, an average of 3 year

• Mobilization success rate

  after all patients accepted stem cell mobilization, an average of 1.5 year

Study Arms (1)

DVRd group

EXPERIMENTAL

Daratumumab combined with bortezomib, lenalidomide and dexamethasone

Drug: DVRd

Interventions

DVRd DRUG

The patients will receive 4 cycles of DVRd induction therapy. After achieving PR or better response, they will receive stem cell mobilization, collection and the following ASCT. Then, the patients will accept 4 cycles of DVRd consolidation and DVR maintenance therapy. Once they sustain MRD negative condition for at least 12 months, the patients will enter the maintenance stage of lenalidomide monotherapy. Otherwise, the triple drug maintenance therapy will be continued for a total of 24 cycles or until disease progression, death, intolerance, withdrawal due to other reasons, or termination/end of the study.

DVRd group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily signing the Informed Consent Form (ICF).
• Age: ≥ 18 years old and \< 70 years old.
• Newly diagnosed MM according to International Myeloma Working Group (IMWG) criteria, with at least one measurable disease: The serum M protein detected by serum protein electrophoresis (SPEP) is ≥ 1g/dL (≥ 10 g/L), or if it is immunoglobulin A (IgA) or immunoglobulin D (IgD) subtype, quantitative levels of total IgA or IgD can be used as a substitute; Or urine M-protein level ≥ 200 mg/24 h; Or if only the serum free light chain (FLC) ratio is abnormal, the affected serum FLC ≥ 100 mg/L (normal FLC ratio: 0.26 to 1.65).
• At least two high-risk cytogenetic abnormalities: t(4;14), t(14;16), t(14;20), del(17p), gain/amp(1q) (the threshold for copy number variation is 20%, and the threshold for translocation is 10%.
• The Eastern Cooperative Oncology Group (ECOG) score is 0, 1, or 2 points. The ECOG score of 3 points due to myeloma bone disease can be included.
• Subjects had not received any anti-MM chemotherapy, extensive pelvic irradiation (more than half of the pelvic area), or anti-MM glucocorticoids, except those who used glucocorticoids for no more than 14 days to control symptoms.
• Total bilirubin \< 1.5 × upper limit of normal (ULN) (total bilirubin in patients with Gilbert's syndrome can be restricted to \<3 × ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN.
• Creatinine clearance rate ≥ 30 mL/min (calculated by cockcroft and Gault formulas).
• Routine blood test within 7 days before the first day of cycle 1 meets the following criteria: white blood cell (WBC) count ≥ 1.5×10\^9/L, absolute neutrophil count ≥ 1.0×10\^9/L, hemoglobin ≥ 75 g/L, and platelet count ≥ 75×10\^9/L (if bone marrow plasmacytes \< 50%) or platelet count ≥ 50×10\^9/L (if bone marrow plasmacytes ≥ 50%).
• Patients receiving erythropoietin, granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), platelet agonists (for example, eltrombopag, thrombopoietin, interleukin-11), must have a 2-week interval between receiving growth factor support and screening assessment.
• Patients receiving blood product transfusions: at least 2 weeks between hemoglobin assessment and the last red blood cell (RBC) transfusion; at least one week between platelet assessment and the last platelet transfusion.
• The subjects have no contraindications of receiving prophylactic anticoagulant drug recommended by the study.
• Female subjects of childbearing age must meet the following two criteria: agree to take effective contraceptive measures from the date of signing the ICF to 3 months after the last administration of the drug; negative serum pregnancy test during screening.

You may not qualify if:

• Primary plasma cell leukemia.
• Secondary amyloidosis.
• Central nervous system (CNS) involvement.
• Patients planning to receive allogeneic hematopoietic stem cell transplantation.
• Patients with \> grade 2 peripheral neuropathy or ≥ grade 2 peripheral neuropathy with pain, regardless of receiving therapy or not.
• Intolerance, allergy or contraindication to glucocorticoids, bortezomib, lenalidomide or daratumumab.
• Clinically significant heart diseases: myocardial infarction before screening, or unstable or uncontrollable diseases related to or affecting cardiac function (such as unstable angina, congestive heart failure, New York Heart Association classification III-IV). Uncontrolled arrhythmia or clinically significant electrocardiogram (ECG) abnormalities. During screening, the 12-lead ECG showed a corrected QT interval (QTc) of \> 470 msec.
• Uncontrolled diabetes mellitus and hypertension.
• Patients with a history of other malignant tumors within 5 years.
• Active human immunodeficiency virus (HIV) infection or positive serum HIV.
• Active hepatitis B or C infection. Hepatitis serological test should be performed during screening. If hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) of patients are positive, DNA polymerase chain reaction (PCR) test should be confirmed as negative before enrollment (After anti hepatitis B virus treatment, DNA PCR test should be confirmed as negative before enrollment). If hepatitis C antibody is positive, RNA PCR test should be performed, and the results should be confirmed as negative before enrollment.
• Pregnant or lactating women.
• Expected life \< 6 months.
• Any uncontrolled gastrointestinal dysfunction that affects the capacity to ingest or absorb the tablets.
• A major surgery history within 2 weeks prior to the start of screening, or will not fully recover from the surgery, or are scheduled for surgery during the study period. Kyphoplasty or vertebroplasty is not considered as a major surgery. Notes: Subjects who plan to undergo surgery under local anesthesia can participate in the study.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences

Tianjin, China

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma; Neoplasm, Residual

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Lugui Qiu

  Institute of Hematology & Blood Diseases Hospital, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lugui Qiu

CONTACT

0086-022-23909171; qiulg@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: September 21, 2023
• First Posted: December 6, 2023
• Study Start: December 1, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 6, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)