This phase II trial studies how well daratumumab works in treating participants with multiple myeloma that has come back after stem cell transplant. Immunotherapy with daratumumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread.
Recruiting
Phase 2
| Drug | Synonyms | Arms |
|---|---|---|
| Daratumumab | Anti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414 | Treatment (daratumumab) |
PRIMARY OBJECTIVES:
I. To estimate the complete remission rate (CRR) by the International Myeloma Working Group
(IMWG) criteria within 9 months post salvage auto-transplant with daratumumab maintenance
therapy starting approximately 3 months post salvage auto-transplant in patients with
relapsed myeloma.
SECONDARY OBJECTIVES:
I. To evaluate progression-free survival (PFS).
EXPLORATORY OBJECTIVES:
I. To discover the impact of daratumumab on graft function and immune reconstitution.
OUTLINE:
Beginning 60-120 days after transplant, participants receive daratumumab intravenously (IV)
over 4-8 hours on days 1, 8, 15 and 22 of courses 1 and 2 and days 1 and 15 of courses 3-6,
then on day 1 of subsequent courses. Courses repeat every 28 days for 2 years in the absence
of disease progression or unacceptable toxicity.
After completion of study treatment, participants are followed up at 30 and 90 days, then
every 4-12 weeks thereafter.
| Name | Type | Description | Interventions |
|---|---|---|---|
| Treatment (daratumumab) | Experimental | Beginning 60-120 days after transplant, participants receive daratumumab IV over 4-8 hours on days 1, 8, 15 and 22 of courses 1 and 2 and days 1 and 15 of courses 3-6, then on day 1 of subsequent courses. Courses repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. |
|
Inclusion Criteria:
- Patient must have had relapsed disease prior to transplant, or undergone previous
autologous stem cell transplant (ASCT), followed by relapse and at least a partial
response to salvage therapy
- Patients must have an Eastern Cooperative Oncology Group (ECOG) status of 0 to 2
- Platelet count >= 50,000/mm^3 (within 5 days before the first dose of the study drug)
- Absolute neutrophil count >= 1000/ mm^3 (no growth factors within 5 days) (within 5
days before the first dose of the study drug)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x upper limit
of normal (ULN) (within 5 days before the first dose of the study drug)
- Creatinine =< 2.5 mg/dL (within 5 days before the first dose of the study drug)
- Recovered (i.e., =< grade 2 toxicity) from the reversible effects of autologous stem
cell transplant (within 5 days before the first dose of the study drug)
- Voluntary written informed consent before performance of any study-related procedure
not part of normal medical care must be obtained, with the understanding that consent
may be withdrawn by the subject at any time without any prejudice to future medical
care
- Left ventricular ejection fraction >= 40%. No uncontrolled arrhythmias
Exclusion Criteria:
- Major surgery within 14 days before the first dose of study drug
- Radiotherapy within 14 days before enrollment
- Non-secretory disease, plasma cell leukemia, or previous allogeneic transplant
- Already achieved CR at time of enrollment
- Known active central nervous system involvement
- Inability or unwillingness to comply with the drug administration requirements
- Female subject is pregnant or lactating
- Seropositive for human immunodeficiency virus (HIV)
- 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)
deoxyribonucleic acid (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
- Seropositive for hepatitis C (except in the setting of a sustained virologic response
[SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy)
- Known severe chronic obstructive pulmonary disease or asthma defined as forced
expiratory volume in 1 second (FEV1) less than 60% of expected
- Infection requiring IV systemic antibiotic therapy within 7 days before cycle 1 day 1
of therapy
- Known allergy to any of the study medications, their analogues, or excipients in the
various formulations
- Failure to have fully recovered (i.e., =< grade 2 toxicity) from the effects of prior
chemotherapy regardless of the interval since last treatment
- Patient is refractory or resistant to daratumumab
- Co-morbid systemic illnesses or other severe concurrent disease that, in the judgment
of the investigator, would make the patient inappropriate for entry into this study or
interfere significantly with the proper assessment of safety and toxicity of the
prescribed regimens
- If patient was unable to tolerate daratumumab in the past
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Complete remission rate (CRR) defined as achieving a negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas, and < 5% plasma cells in bone marrow |
| Time Frame: | At course 6 of therapy |
| Safety Issue: | |
| Description: | The student t-test/Wilcoxon rank test and analysis of variance (ANOVA)/Kruskal-Wallis test, or chi-squared test/Fisher's exact test will be used to test associations between the response and the prognostic factors. Complete remission will be estimated along with a 95% credible interval. |
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | M.D. Anderson Cancer Center |
June 30, 2020
