Multiple Myeloma
Conditions
Keywords
newly diagnosed MM (NDMM) patients in post-autologous stem cell transplant (ASCT) setting
Brief summary
This phase II trial tests daratumumab given at a reduced frequency with lenalidomide for maintenance therapy for the cost effective treatment of patients with multiple myeloma post stem cell transplant. Darzalex Faspor (also known as Daratumumab-hyaluronidase) is a combination of two drugs used alone or with other drugs to treat adults with certain types of multiple myeloma or light chain amyloidosis. Daratumumab binds to a protein called CD38, which is found on some types of immune cells and cancer cells, including myeloma cells. Daratumumab may block CD38 and help the immune system kill cancer cells. Hyaluronidase allows daratumumab to be given by injection under the skin. Daratumumab and hyaluronidase can be given in less time than daratumumab alone, which is given as an infusion. Lenalidomide may stop or slow cancer cells by blocking the growth of new blood vessels necessary for tumor growth. Daratumumab-hyaluronidase is typically given every 4 weeks per standard of care. Giving it every 8 weeks for the first year followed by every 16 weeks for years 2 through 4 in combination with lenalidomide may be equally as effective and reduce costs and treatment visits for patients with multiple myeloma post stem cell transplant.
Interventions
Daratumumab- will be administered at a dose of 1800 mg/30,000 units subcutaneously, every 8 weeks throughout Year 1 (injection to occur on day 1 of every other 28-day cycle for Cycle 1 through Cycle 11); throughout years 2 through 4 (beginning at Cycle 15, ending at Cycle 47), Daratumumab injections will occur every fourth cycle.
DRUGLenalidomide
Patients are scheduled to take an oral dose of Lenalidomide once each day (QD), starting at 10 mg per day for the first 3 months with an increase to 15 mg per day subsequently, if tolerated. Patients will do this continuously, until progressive disease or unacceptable adverse event
Sponsors
Eden Biltibo
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Signed and dated written informed consent * Male or female newly diagnosed multiple myeloma (NDMM) patients 18 to 70 years old on the day of signing informed consent who had ASCT with post-ASCT response of partial response (PR) or better as defined by International Myeloma Working Group (IMWG). The induction regimen should include a proteasome inhibitors (PI), immunomodulatory drugs (IMiD) and anti-CD38 monoclonal antibody * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 * Patients with high-risk and international staging system (ISS) stage-III disease in 15% of the intent to treat population. Patients with 1q gain, 1p deletion, del17p, t\[4;14\], or t\[14;16\] by fluorescence in situ hybridization \[FISH\] will be categorized as having high risk disease * Absolute neutrophil count, ≥ 1.0 × 10\^9/L * Platelets ≥ 75,000/μL * Hemoglobin level ≥ 7.5 g/dL * Total bilirubin \< 1.5 times institutional upper limit of normal (ULN) (if patient has known history of Gilbert's syndrome, total bilirubin will not be used as an
Exclusion criteria
) * Corrected serum calcium, ≤ 14.0 mg/dL (≤ 3.5 mmol/L) * Platelet count, ≥ 50 × 10\^9/L (≥ 50 × 10\^9/L if ≥ 50% of the bone marrow was infiltrated with multiple myeloma \[MM\] cells) * Alanine aminotransferase and aspartate aminotransferase levels \< 2.5 times the upper limit of normal * Creatinine clearance ≥ 30 mL/min (per institutional standard) * All ASCT-related toxicities must have recovered to ≤ grade 1 (except for alopecia, fatigue and amenorrhea) prior to first randomization * Mucositis and gastrointestinal symptoms must have resolved to ≤ grade 1 * Patients must not be pregnant due to potential harm to the fetus from daratumumab and lenalidomide. All patients of childbearing potential must have a negative test result via blood test or urine study with a sensitivity of at least 50 mIU/mL within 10-14 days prior to the first dose of lenalidomide and again within 24 hours prior to the first dose of lenalidomide. Patients of childbearing potential must also agree to ongoing pregnancy testing while on treatment. A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: \* 1) has achieved menarche at some point, \* 2) has not undergone a hysterectomy or bilateral oophorectomy, or \* 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). Patients of childbearing potential must either abstain from sexual intercourse for the duration of their participation in the study or agree to use TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME for \* 1) at least 28 days before starting study treatment; \* 2) while participating in the study; \* 3) during dose interruptions; and \* 4) for at least 3 months after the last dose of protocol treatment. Patients must also agree to not breastfeed during this same time period. Men must agree to either abstain from sexual intercourse for the duration of their participation in the study or use a latex condom during sexual contact with a partner of childbearing potential while participating in the study and for 3 months after the last dose of lenalidomide even if they have had a successful vasectomy. Patients must also agree to abstain from donating sperm, even if they have had a successful vasectomy, or eggs while on study treatment and for 3 months after the last dose of protocol. Patients must agree to abstain from donating blood during study participation and for at least 28 days after last dose of lenalidomide
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants with minimal residual disease (MRD) negative status | 2 years | Determined by next generation sequencing or color flow cytometry per Euroflow standard procedure at sensitivity threshold of 10\^-5. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess MRD dynamics at enrollment, day + 365 and at 2 years, including rate of sustained MRD negativity. | At enrollment, day + 365 and at 2 years | — |
| Progression-free Survival (PFS) measured from day + 100 post-ASCT. | From day + 100 post-autologous stem cell transplant, up to 6 months post treatment | Noninferiority will be assessed by estimating the two-sided 95% confidence interval for the between-group difference in crude rates of 2-year progression-free survival and checking that the lower bound was not lower than -10%. Will conduct the analysis of progression-free survival by using Kaplan-Meier survival curves. |
| Assess patient satisfaction on treatment arm using Functional Assessment of Cancer Therapy (FACT)-G item. | At baseline, cycle 13 day 1, cycle 25 day 1, cycle 37 day 1 and at day 28 follow up (cycle length = 28 days) | Using Functional Assessment of Cancer Therapy-G item. Descriptive analysis will be used to summarize the changes. |
Countries
United States
Contacts
CONTACTVanderbilt-Ingram Service Information Program
PRINCIPAL_INVESTIGATOREden Biltibo, MD, PhD
Vanderbilt-Ingram Cancer Center
Outcome results
None listed