S1803, Daratumumab/rHuPh20 +/- Lenalidomide as Post-ASCT Maintenance for MM w/MRD to Direct Therapy Duration

Overview

Patients are enrolled to screening (Reg Step 1) prior to or after ASCT but prior to Reg Step 2. Patients are followed until they will begin Maintenance and then registered to Reg Step 2 (first randomization). Patients are randomized between Lenalidomide for 2 years and Lenalidomide + Daratumumab/rHuPH20. After 2 years of Maintenance, MRD is assessed to guide further therapy. MRD-positive patients will continue with the assigned treatment. MRD-negative patients will be further randomized (Reg Step 3) to either continue or discontinue the assigned treatment. Patients are treated for up to 7 years from Step 2 reg and followed for up to 15 years.

SparkCures ID 1019
Trial Phase Phase 3
Enrollment 1100 Patients
Treatments
Trial Sponsors
  • Southwest Oncology Group
Trial Collaborators
  • National Cancer Institute (NCI)
  • Janssen Research & Development
  • Adaptive Biotechnologies
NCT Identifier

NCT04071457

Am I Eligible?

The following criteria is a partial list of reasons why patients may or may not be eligible to participate in this clinical trial. Further evaluation with a medical professional will be required to determine full eligibility.

The following criteria is provided for health care professionals.

Registration Step 1 Except where otherwise indicated below that test is required in a shorter timeframe, all tests for establishing baseline disease status must be completed within 60 days prior to registration. All test results must be documented on the Baseline Tumor Assessment Form for Multiple Myeloma and the Onstudy Form.

Inclusion Criteria

  • Patients must have had a confirmed diagnosis of symptomatic multiple myeloma (See Section 4.1) that required systemic induction therapy prior to autologous stem cell transplantation (ASCT).
  • Patients with disease measurable by serum light chain assay alone are eligible (defined as >/= 100 mg/L on involved light chain).
  • Patients 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.
  • Patients must have initiated induction therapy within 12 months prior to registration Step 1 and have received at least two cycles of induction therapy.
  • Patients must be willing and able to take DVT prophylaxis (aspirin, low molecular weight heparin, warfarin, or equivalent oral anticoagulation).
  • Patients must be >/= 18 and
  • Patients must have history and physical exam within 28 days prior to registration.
  • Patients must have Zubrod Performance Status
  • Patients must have evidence of adequate renal function, as defined by (1) creatinine clearance (CrCl) >/= 30 mL/min., as measured by a 24-hour urine collection, or estimated by the Cockcroft and Gault formula, or (2) serum creatinine < 2.5 mg/dL. Values must be obtained within 28 days prior to registration.
  • Patients must have adequate hepatic function defined by the following within 42 days prior to registration:
    • Total bilirubin
    • AST and ALT
  • Patients must meet one of the following criteria:
    • Be acceptable for transplant per institutional guidelines and the criteria evidencing this must be documented on the S1803 Onstudy Form. (See Appendix 18.3 for standard transplant eligibility guidelines. Note that these are guidelines and not required criteria.) OR
    • Have completed autologous stem cell transplant within 180 days prior to registration (see also Section 5.2a).
  • Patient's with 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.
  • Patients must be able to take and swallow oral medication (capsules) whole. Patients may not have any known impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
  • For 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.
  • Patients must submit specimens for MRD as outlined in Section 15.1. See Section 15.1 for further information, including specimen submission timepoints. Note that patients are not ineligible based solely on archival specimens being unavailable.
  • Patients must be offered participation in specimen banking for future research. With patient's consent, specimens must be submitted as outlined in Section 15.2.
  • Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.
  • As a part of the OPEN registration process (see Section 13.3 for OPEN access instructions) the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.

Exclusion Criteria

  • 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 >/= 0.5g/dL) or urine (defined as >/= 200 mg/24h). Patients with plasma cell leukemia are not eligible.
  • Patients must not have any organ involvement by amyloidosis or evidence of amyloidosis related organ dysfunction.
  • Patients must not have progressive disease at any time prior to registration.
  • Patients must not be refractory to either lenalidomide or daratumumab/rHuPH20.
  • Patients must not be intolerant to either lenalidomide or daratumumab/rHuPH20.
  • Patients must not have received any investigational agents within 14 days prior to registration.
  • Patients must not have chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) < 50% of predicted normal. FEV1 is required for patients suspected of having chronic obstructive pulmonary disease and are not eligible if FEV1 is < 50% of predicted normal.
  • Patients must not have moderate or severe persistent asthma within the past 2 years and must not have currently uncontrolled asthma of any classification.
  • Patients must not have had prior autograft or allograft, or prior organ transplant requiring immunosuppressive therapy.
  • Patients must not have known allergy to any of the study drugs.
  • Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment are not eligible.
  • Patients 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.
  • Patients 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.
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years.
  • Patients 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 >/= 2), intra-cardiac defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (>/= Grade 3), or known psychiatric illness that would limit study compliance.

Registration Step 2 - First Randomization (Post-ASCT, Pre-Maintenance)

Inclusion Criteria:

  • Patients must have completed ASCT within 180 days prior to registering to Step 2.
  • Patients must have one of the following performed within 60 days prior to registration for disease assessment: diagnostic quality skeletal survey, whole body CT scan, MRI, or PET.
  • Patients must have Zubrod Performance Status
  • Patients must have adequate bone marrow function as evidenced by platelets >/= 75,000/mm3 and ANC >/= 1,000/mm3 within 28 days prior to first randomization:
  • Patients must have adequate hepatic function defined by the following within 28 days prior to first randomization:
  • Total bilirubin
  • Patients must have evidence of adequate renal function, as defined by creatinine clearance (CrCl) >/= 30 mL/min., as measured by a 24-hour urine collection, or estimated by the Cockcroft and Gault formula, or have a serum creatinine < 2.5 mg/dL within 28 days prior to first randomization.
  • All ASCT-related toxicities must have recovered to
  • Mucositis and gastrointestinal symptoms must have resolved to
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to registration.
  • FCBP must agree to have a second pregnancy test within 24 hours prior to starting Cycle 1. Further, FCBP must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide. FCBP must also agree to ongoing pregnancy testing and must agree to not become pregnant for at least 3 months after the last dose of study treatment.
  • Men must agree to use a latex condom during sexual contact with a FCBP, even if they have had a successful vasectomy, during the study treatment and for 3 months after the last dose of study treatment.
  • Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.

Exclusion Criteria:

  • Patients must not have received any other maintenance therapy post-ASCT and prior to Step 2 registration.
  • Patients must not have had progressive disease between induction and registration to Registration Step 2. (See Section 10.1b).

Registration Step 3 - Second Randomization (Post 24 Months Maintenance)

Inclusion Criteria:

  • Patients must have completed 24 cycles of protocol maintenance with either lenalidomide or lenalidomide + daratumumab/rHuPH20.
  • Patients must have 24-month MRD by NGS test results available and must be MRD negative. Patients whose PCR results are indeterminable will be considered to have positive results.
  • Patients must be in very good partial remission (VGPR) or better by IMWG response criteria (see Section 10.1b).

US Trial Locations

Accepting Patients

The following is a listing of trial locations that are open and accepting patients.

St. Edward Mercy Medical Center

Fort Smith, AR

Abbott-Northwestern Hospital

Minneapolis, MN

Saint Louis Cancer and Breast Institute (South City)

St. Louis, MO

Mercy Hospital South

St. Louis, MO

Siteman Cancer Center - South County

St. Louis, MO

Missouri Baptist Medical Cancer Center

St. Louis, MO

Missouri Baptist Sullivan Hospital

Sullivan, MO

Missouri Baptist Outpatient Center (Sunset Hills)

Sunset Hills, MO

Mercy Hospital Washington

Washington, MO

Health Partners Inc.

Minneapolis, MN

Saint John's Hospital - Healtheast

Maplewood, MN

CoxHealth South Hospital

Springfield, MO

Minnesota Oncology and Hematology PA (Maplewood)

Maplewood, MN

Fairview Maple Grove Medical Center

Maple Grove, MN

Fairview Ridges Hospital

Burnsville, MN

Fairview Southdale Hospital

Edina, MN

Mercy Hospital

Coon Rapids, MN

Cambridge Medical Center

Cambridge, MN

Monticello Cancer Center

Monticello, MN

Unity Hospital

Fridley, MN

New Ulm Medical Center

New Ulm, MN

St. Joseph Oncology

St. Joseph, MO

Mercy Hospital Springfield

Springfield, MO

North Memorial Medical Health Center

Robbinsdale, MN

Phelps County Regional Medical Center

Rolla, MO

Saint Francis Hospital Cancer Center

Greenville, SC

Saint Francis Hospital

Greenville, SC

Ralph H Johnson VA Medical Center

Charleston, SC

Oklahoma Cancer Specialists and Research Institute (Tulsa)

Tulsa, OK

Mercy Hospital Oklahoma City

Oklahoma City, OK

University of Oklahoma Health Sciences Center

Oklahoma City, OK

Methodist Hospital - Nebraska Methodist Health System

Omaha, NE

FirstHealth of the Carolinas (Moore Regional Hosiptal)

Pinehurst, NC

Freeman Health System

Joplin, MO

Siteman Cancer Center at Saint Peters Hospital

Saint Peters, MO

Capital Region Medical Center (Goldschmidt Cancer Center)

Jefferson City, MO

Mercy Hospital Saint Louis

Creve Coeur, MO

Siteman Cancer Center at West County Hospital

Creve Coeur, MO

Saint Louis Cancer and Breast Institute

Ballwin, MO

Saint Francis Medical Center (Cape Girardeau)

Cape Girardeau, MO

CoxHealth Cancer Center

Branson, MO

Parkland Health Center (Bonne Terre)

Bonne Terre, MO

Saint John's Clinic-Rolla-Cancer and Hematology

Rolla, MO

Southeast Cancer Center

Cape Girardeau, MO

Sainte Genevieve County Memorial Hospital

Sainte Genevieve, MO

Hennepin County Medical Center

Minneapolis, MN

Fairview Northland Medical Center

Princeton, MN

Illinois CancerCare

Peoria, IL

Good Samaritan Regional Health Center

Mount Vernon, IL

Cancer Care Specialists of Illinois (Swansea)

Swansea, IL

Marjorie Weinberg Cancer Center at Loyola-Gottlieb

Melrose Park, IL

Springfield Clinic

Springfield, IL

Southern Illinois University School of Medicine

Springfield, IL

Illinois CancerCare (Princeton)

Princeton, IL

Valley Radiation Oncology

Peru, IL

Memorial Medical Center

Springfield, IL

Methodist Medical Center of Illinois

Peoria, IL

Illinois CancerCare (Pekin)

Pekin, IL

Illinois CancerCare (Macomb)

Macomb, IL

Illinois CancerCare (Ottawa)

Ottawa, IL

Loyola Center for Cancer Care and Research

Orland Park, IL

Illinois CancerCare (Peru)

Peru, IL

McFarland Clinic PC (Marshalltown)

Marshalltown, IA

McFarland Clinic PC (Jefferson)

Jefferson, IA

McFarland Clinic PC (Trinity Cancer Center)

Fort Dodge, IA

McFarland Clinic PC (Boone)

Boone, IA

McFarland Clinic PC

Ames, IA

Mary Greeley Medical Center

Ames, IA

Loyola University Medical Center - Cardinal Bernardin Cancer Center

Maywood, IL

Cancer Care Specialists of Central Illinois

Decatur, IL

Fairview Lakes Medical Center

Wyoming, MN

Western Illinois Cancer Treatment Center

Galesburg, IL

Minnesota Oncology and Hematology PA (Woodbury)

Woodbury, MN

Ridgeview Medical Center

Waconia, MN

Lakeview Hospital

Stillwater, MN

Rice Memorial Hospital

Willmar, MN

Regions Hospital

St. Paul, MN

Park Nicollet Clinic (Saint Louis Park)

St. Louis Park, MN

Saint Francis Regional Medical Center

Shakopee, MN

United Hospital

St. Paul, MN

Illinois CancerCare-Dixon

Dixon, IL

Illinois CancerCare (Galesburg)

Galesburg, IL

Illinois CancerCare (Bloomington)

Bloomington, IL

Illinois CancerCare (Kewanee)

Kewanee, IL

Illinois CancerCare (Eureka)

Eureka, IL

Crossroads Cancer Center

Effingham, IL

Decatur Memorial Hospital

Decatur, IL

Memorial Hospital of Carbondale

Carbondale, IL

Centralia Oncology Clinic

Centralia, IL

Illinois CancerCare (Carthage)

Carthage, IL

SIH Cancer Institute

Carterville, IL

Illinois CancerCare (Canton)

Canton, IL

Loyola Center for Health at Burr Ridge

Burr Ridge, IL

Cancer Center of Western Wisconsin

New Richmond, WI

Arkansas
St. Edward Mercy Medical Center

Fort Smith, AR

California
Florida
Illinois
Illinois CancerCare (Bloomington)

Bloomington, IL

Loyola Center for Health at Burr Ridge

Burr Ridge, IL

Illinois CancerCare (Canton)

Canton, IL

Memorial Hospital of Carbondale

Carbondale, IL

SIH Cancer Institute

Carterville, IL

Illinois CancerCare (Carthage)

Carthage, IL

Centralia Oncology Clinic

Centralia, IL

Cancer Care Specialists of Central Illinois

Decatur, IL

Decatur Memorial Hospital

Decatur, IL

Illinois CancerCare-Dixon

Dixon, IL

Crossroads Cancer Center

Effingham, IL

Illinois CancerCare (Eureka)

Eureka, IL

Illinois CancerCare (Galesburg)

Galesburg, IL

Western Illinois Cancer Treatment Center

Galesburg, IL

Illinois CancerCare (Kewanee)

Kewanee, IL

Illinois CancerCare (Macomb)

Macomb, IL

Loyola University Medical Center - Cardinal Bernardin Cancer Center

Maywood, IL

Marjorie Weinberg Cancer Center at Loyola-Gottlieb

Melrose Park, IL

Good Samaritan Regional Health Center

Mount Vernon, IL

Loyola Center for Cancer Care and Research

Orland Park, IL

Illinois CancerCare (Ottawa)

Ottawa, IL

Illinois CancerCare (Pekin)

Pekin, IL

Illinois CancerCare

Peoria, IL

Methodist Medical Center of Illinois

Peoria, IL

Illinois CancerCare (Peru)

Peru, IL

Valley Radiation Oncology

Peru, IL

Illinois CancerCare (Princeton)

Princeton, IL

Southern Illinois University School of Medicine

Springfield, IL

Springfield Clinic

Springfield, IL

Memorial Medical Center

Springfield, IL

Cancer Care Specialists of Illinois (Swansea)

Swansea, IL

Iowa
Mary Greeley Medical Center

Ames, IA

McFarland Clinic PC

Ames, IA

McFarland Clinic PC (Boone)

Boone, IA

McFarland Clinic PC (Trinity Cancer Center)

Fort Dodge, IA

McFarland Clinic PC (Jefferson)

Jefferson, IA

McFarland Clinic PC (Marshalltown)

Marshalltown, IA

Minnesota
Fairview Ridges Hospital

Burnsville, MN

Cambridge Medical Center

Cambridge, MN

Mercy Hospital

Coon Rapids, MN

Fairview Southdale Hospital

Edina, MN

Unity Hospital

Fridley, MN

Fairview Maple Grove Medical Center

Maple Grove, MN

Minnesota Oncology and Hematology PA (Maplewood)

Maplewood, MN

Saint John's Hospital - Healtheast

Maplewood, MN

Abbott-Northwestern Hospital

Minneapolis, MN

Hennepin County Medical Center

Minneapolis, MN

Health Partners Inc.

Minneapolis, MN

Monticello Cancer Center

Monticello, MN

New Ulm Medical Center

New Ulm, MN

Fairview Northland Medical Center

Princeton, MN

North Memorial Medical Health Center

Robbinsdale, MN

Saint Francis Regional Medical Center

Shakopee, MN

Park Nicollet Clinic (Saint Louis Park)

St. Louis Park, MN

Regions Hospital

St. Paul, MN

United Hospital

St. Paul, MN

Lakeview Hospital

Stillwater, MN

Ridgeview Medical Center

Waconia, MN

Rice Memorial Hospital

Willmar, MN

Minnesota Oncology and Hematology PA (Woodbury)

Woodbury, MN

Fairview Lakes Medical Center

Wyoming, MN

Missouri
Saint Louis Cancer and Breast Institute

Ballwin, MO

Parkland Health Center (Bonne Terre)

Bonne Terre, MO

CoxHealth Cancer Center

Branson, MO

Saint Francis Medical Center (Cape Girardeau)

Cape Girardeau, MO

Southeast Cancer Center

Cape Girardeau, MO

Siteman Cancer Center at West County Hospital

Creve Coeur, MO

Mercy Hospital Saint Louis

Creve Coeur, MO

Capital Region Medical Center (Goldschmidt Cancer Center)

Jefferson City, MO

Freeman Health System

Joplin, MO

Phelps County Regional Medical Center

Rolla, MO

Saint John's Clinic-Rolla-Cancer and Hematology

Rolla, MO

Siteman Cancer Center at Saint Peters Hospital

Saint Peters, MO

Sainte Genevieve County Memorial Hospital

Sainte Genevieve, MO

Mercy Hospital Springfield

Springfield, MO

CoxHealth South Hospital

Springfield, MO

St. Joseph Oncology

St. Joseph, MO

Saint Louis Cancer and Breast Institute (South City)

St. Louis, MO

Mercy Hospital South

St. Louis, MO

Siteman Cancer Center - South County

St. Louis, MO

Missouri Baptist Medical Cancer Center

St. Louis, MO

Missouri Baptist Sullivan Hospital

Sullivan, MO

Missouri Baptist Outpatient Center (Sunset Hills)

Sunset Hills, MO

Mercy Hospital Washington

Washington, MO

Nebraska
Methodist Hospital - Nebraska Methodist Health System

Omaha, NE

North Carolina
FirstHealth of the Carolinas (Moore Regional Hosiptal)

Pinehurst, NC

Oklahoma
University of Oklahoma Health Sciences Center

Oklahoma City, OK

Mercy Hospital Oklahoma City

Oklahoma City, OK

Oklahoma Cancer Specialists and Research Institute (Tulsa)

Tulsa, OK

Oregon
South Carolina
Ralph H Johnson VA Medical Center

Charleston, SC

Saint Francis Hospital

Greenville, SC

Saint Francis Hospital Cancer Center

Greenville, SC

Wisconsin
Cancer Center of Western Wisconsin

New Richmond, WI

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