Title
Phase III Study of Daratumumab/rHuPH20 (NSC-810307) + Lenalidomide or Lenalidomide as Post-Autologous Stem Cell Transplant Maintenance Therapy in Patients With Multiple Myeloma (MM) Using Minimal Residual Disease to Direct Therapy Duration (DRAMMATIC Study)

Description
Phase III Study of Daratumumab/rHuPH20 (NSC-810307) + Lenalidomide or Lenalidomide as Post-Autologous Stem Cell Transplant Maintenance Therapy in Patients with Multiple Myeloma (MM) Using Minimal Residual Disease to Direct Therapy Duration

Objective
The purpose of this study is to compare the usual maintenance treatment alone (lenalidomide until the disease progresses or you cannot tolerate it) to using the drug daratumumab/rHuPH20 plus the usual treatment. The addition of daratumumab/rHuPH20 to the usual treatment could help you live longer after your stem cell transplant. But, it could also cause side effects

Treatment Lenalidomide alone after your stem cell transplant or lenalidomide and daratumumab/rHuPH20

Key Eligibility
Must have had a confirmed diagnosis of symptomatic multiple myeloma that required systemic induction therapy prior to autologous stem cell transplantation (ASCT)

Patients with smoldering myeloma are not eligible. Patients with purely non-secretory MM as measured by electrophoresis and immunofixation and the absence of Bence Jones proteins in the urine are not eligible. Patients must have measurable M protein in the serum (defined as greater than or equal to 0.5g/dL) or urine (defined as greater than or eqal to 200 mg/24h). Patients with plasma cell leukemia are not eligible

Patients with disease measurable by serum light chain assay alone are eligible

Must not have any organ involvement by amyloidosis or evidence of amyloidosis related organ dysfunction

Must not have progressive disease at any time prior to registration

Must not be refractory or intolerant to either lenalidomide or daratumumab/rHuPH20

Must have initiated induction therapy within 12 months prior to registration Step 1 and have received at least two cycles of induction therapy

Must be registered to Step 1 prior to registration to Step 2. Registration to Step 1 may take place prior to or after autologous stem cell transplant (ASCT), but after completion of induction therapy

Must be willing and able to take DVT prophylaxis (aspirin, low molecular weight heparin, warfarin, or equivalent oral anticoagulation)

Zubrod Performance Status 0-2

Must be 18 years of age and less than or equal to 75

Must have adequate renal and hepatic function as defined by the protocol

Must not have chronic obstructive pulmonary disease as defined by the protocol

Must not have moderate or severe persistent asthma within the past 2 years and must not have currently uncontrolled asthma of any classification

Must meet one of the following criteria: Be acceptable for transplant per institutional guidelines OR completed autologous stem cell transplant within 180 days prior to registration

Must not have had prior autograft or allograft, or prior organ transplant requiring immunosuppressive therapy

Human immunodeficiency virus (HIV) are eligible providing they are on effective antiretroviral therapy and have undetectable viral load at their most previous viral load test and within 6 months prior to registration

Uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment are not eligible

Must not have known central nervous system (CNS) involvement with multiple myeloma, defined as CSF positivity for plasma cells at any time or a parenchymal CNS plasmacytoma at time of enrollment. Lumbar puncture is not required

Must not be seropositive for hepatitis C (except in the setting of sustained virologic response, defined as undetectable viral load at least 12 weeks after completion of antiviral therapy). HCV testing is only required if clinically indicated or if the patient has a history of HCV

Must be able to take and swallow oral medication (capsules) whole

Must not have any uncontrolled intercurrent illness including (not limited to): Symptomatic CHF (NYHA III/IV), unstable angina pectoris or coronary angioplasty, or stenting within 6 months prior to registration, Unstable cardiac arrhythmia (ongoing cardiac dysrhythmias of NCI CTCAE v5.0 Grade greater than or equal to 2), intra-cardiac defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (greater than or equal to Grade 3), or known psychiatric illness that would limit study compliance

Patients who have not yet received transplant: Patients must be willing and able to return to the transplant center for their assigned treatment after randomization. Note that patients need not have a direct relationship with the transplant center in order to register

Step 2 and 3 have eligibility requirements as defined by the protocol

Applicable Disease Sites
Multiple Myeloma

Participating Institutions
Bellin Memorial Hospital/Cancer Team at Bellin Health; Mercy Health Systems, Janesville ; Oconomowoc Memorial Hospital, Waukesha Memorial; UW Health 1 S. Park Medical Center; UW Health University Hospital