Blood Cancer
EA9213
Testing the use of Daratumumab-Hyaluronidase in Persistent or Recurrent T Cell Acute Lymphoblastic Leukemia (T-ALL) following Treatment with Chemotherapy
STATUS: Active
This phase II trial tests whether daratumumab-hyaluronidase works in treating T cell acute lymphoblastic leukemia (T-ALL) that persists after treatment (persistent) or has come back (recurrent) in patients who have received treatment with chemotherapy. Daratumumab targets and binds to a protein called CD38 that are present on cancer cells, while hyaluronidase helps to deliver daratumumab to CD38-expressing cancer cells and kill them.
- PREREGISTRATION (STEP 0):
- Patient must be able to undergo diagnostic bone marrow aspirate following preregistration if not performed previously * NOTE: Bone marrow aspirate must be submitted to Dr. Brent Wood’s laboratory at Children’s Hospital Los Angeles for central assessment of the establishment of MRD status to confirm patient’s eligibility for registration to Step 1
- Bone marrow must be from the first pull (initial or redirect needle) and specimens must contain sufficient blast cells. In cases where the bone marrow aspiration is not adequate or the bone marrow examination has already been performed prior to study consent and enrollment on Step 0, peripheral blood can be submitted regardless of peripheral blast percentage Dr. Brent Wood’s laboratory at Children’s Hospital Los Angeles will forward results within 48 hours (two business days) of receipt of the specimen to the submitting institution * NOTE: If MRD status testing was performed previously as part of standard of care at Dr. Brent Wood’s laboratory, eligible patients can proceed from Step 0 preregistration directly to Step 1 registration after forwarding MRD report to Dr. Brent Wood for verification and uploading report via Medidata Rave. MRD testing will not be accepted from other laboratories. Step 0 preregistration cannot be bypassed. MRD must be quantified within 14 days prior to starting daratumumab treatment on study
- Patient must be >= 18 years of age
- Patient must have documented T cell ALL and must be in first or later hematologic complete remission (CR) or complete remission incomplete (CRi) after a minimum of 2 blocks of intensive chemotherapy * Patients >= 65 years of age that the physician judges to be unfit for 2 blocks of intensive chemotherapy may enroll after one cycle of chemotherapy as long as they are in CR or CRi at least 28 days after initiation of Leukemia directed therapy. These patient must have received at least 4 weekly doses of vincristine and steroids
- REGISTRATION (STEP 1):
- Patients in hematologic CR or CRi must have persistent or recurrent MRD >= 10^-4
- Institution must have received central MRD status test results confirming persistent or recurrent MRD >= 10^-4 by flow cytometry
- Patient may have undergone a prior allogeneic stem cell transplant, but patient may not have grafts versus host disease (GVHD) that requires ongoing immunosuppressive therapy. Patient may receive prednisone if the dose is =< 10 mg per day
- Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used * All patients of childbearing potential must have a blood test or urine study within 14 days prior to Step 1 registration to rule out pregnancy * 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 must not expect to conceive or father children by using an accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and continue to 3 months after the last dose of protocol treatment. Patients must also agree to abstain from donating sperm, even if they have had a successful vasectomy, or donating eggs while on study treatment and for 3 months after the last dose of protocol treatment
- Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
- Absolute neutrophil count (ANC) >= 750/mL (must be obtained =< 7 days prior to Step 1 registration)
- Platelets >= 75,000/mL (must be obtained =< 7 days prior to Step 1 registration)
- Total or direct bilirubin =< 2 mg/dL (must be obtained =< 7 days prior to Step 1 registration)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate-pyruvate transaminase [SGPT]) =< 3.0 x institutional upper limit of normal (ULN) (must be obtained =< 7 days prior to Step 1 registration)
- Creatinine =< 1.5 x institutional ULN or Creatinine Clearance > 30 ml/min (must be obtained =< 7 days prior to Step 1 registration)
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- Patients with prior central nervous system (CNS) involvement are eligible as long as they do not have active CNS involvement at time of Step 1 registration
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
United States
AL
Birmingham
University of Alabama at Birmingham Cancer Center
Contact: Site Public Contact
Email: tmyrick@uab.edu
AR
Ft. Smith
Mercy Hospital Fort Smith
Contact: Site Public Contact
Little Rock
CARTI Cancer Center
Contact: Site Public Contact
Email: Research@CARTI.com
AZ
Scottsdale
Mayo Clinic in Arizona
Contact: Site Public Contact
FL
Jacksonville
Mayo Clinic in Florida
Contact: Site Public Contact
University of Florida Health Science Center - Jacksonville
Contact: Site Public Contact
Email: trials@cancer.ufl.edu
IL
Alton
Saint Anthony's Health
Contact: Site Public Contact
Aurora
Rush - Copley Medical Center
Contact: Site Public Contact
Email: Cancer.Research@rushcopley.com
Centralia
Saint Mary's Hospital
Contact: Site Public Contact
Email: ecog.rss@jimmy.harvard.edu
Chicago
Northwestern University
Contact: Site Public Contact
Email: cancer@northwestern.edu
University of Chicago Comprehensive Cancer Center
Contact: Site Public Contact
Email: cancerclinicaltrials@bsd.uchicago.edu
Danville
Carle at The Riverfront
Contact: Site Public Contact
Email: Research@Carle.com
Effingham
Carle Physician Group-Effingham
Contact: Site Public Contact
Email: Research@carle.com
Mattoon
Carle Physician Group-Mattoon/Charleston
Contact: Site Public Contact
Email: Research@carle.com
Mount Vernon
Good Samaritan Regional Health Center
Contact: Site Public Contact
Urbana
Carle Cancer Center
Contact: Site Public Contact
Email: Research@carle.com
The Carle Foundation Hospital
Contact: Site Public Contact
Email: Research@carle.com
Yorkville
Rush-Copley Healthcare Center
Contact: Site Public Contact
Email: Cancer.Research@rushcopley.com
KS
Garden City
Central Care Cancer Center - Garden City
Contact: Site Public Contact
Email: aroland@kccop.org
Great Bend
Central Care Cancer Center - Great Bend
Contact: Site Public Contact
Email: aroland@kccop.org
MA
Boston
Dana-Farber Cancer Institute
Contact: Site Public Contact
MN
Rochester
Mayo Clinic in Rochester
Contact: Site Public Contact
MO
Ballwin
Saint Louis Cancer and Breast Institute-Ballwin
Contact: Site Public Contact
Bolivar
Central Care Cancer Center - Bolivar
Contact: Site Public Contact
Email: aroland@kccop.org
Branson
Cox Cancer Center Branson
Contact: Site Public Contact
Joplin
Freeman Health System
Contact: Site Public Contact
Email: LJCrockett@freemanhealth.com
Mercy Hospital Joplin
Contact: Site Public Contact
Email: esmeralda.carrillo@mercy.net
Osage Beach
Lake Regional Hospital
Contact: Site Public Contact
Email: clinicaltrials@lakeregional.com
Rolla
Delbert Day Cancer Institute at PCRMC
Contact: Site Public Contact
Email: research@phelpshealth.org
Mercy Clinic-Rolla-Cancer and Hematology
Contact: Site Public Contact
Saint Joseph
Heartland Regional Medical Center
Contact: Site Public Contact
Email: linda.schumacher@mymlc.com
Saint Louis
Mercy Hospital Saint Louis
Contact: Site Public Contact
Mercy Hospital South
Contact: Site Public Contact
Email: Danielle.Werle@mercy.net
Saint Louis Cancer and Breast Institute-South City
Contact: Site Public Contact
Springfield
CoxHealth South Hospital
Contact: Site Public Contact
Mercy Hospital Springfield
Contact: Site Public Contact
Washington
Mercy Hospital Washington
Contact: Site Public Contact
NC
Winston-Salem
Wake Forest University Health Sciences
Contact: Site Public Contact
NY
Rochester
University of Rochester
Contact: Site Public Contact
OH
Cleveland
Case Western Reserve University
Contact: Site Public Contact
Email: CTUReferral@UHhospitals.org
OK
Oklahoma City
Mercy Hospital Oklahoma City
Contact: Site Public Contact
University of Oklahoma Health Sciences Center
Contact: Site Public Contact
Email: ou-clinical-trials@ouhsc.edu
PR
Bayamon
Cancer Center-Metro Medical Center Bayamon
Contact: Site Public Contact
Puerto Rico Hematology Oncology Group
Contact: Site Public Contact
Manati
Doctors Cancer Center
Contact: Site Public Contact
San Juan
Centro Comprensivo de Cancer de UPR
Contact: Site Public Contact
Email: ecog.rss@jimmy.harvard.edu
PROncology
Contact: Site Public Contact
Email: info@PRoncology.com
San Juan City Hospital
Contact: Site Public Contact
San Juan Community Oncology Group
Contact: Site Public Contact
WA
Seattle
FHCC South Lake Union
Contact: Site Public Contact
Fred Hutchinson Cancer Center
Contact: Site Public Contact
University of Washington Medical Center - Montlake
Contact: Site Public Contact
WI
Eau Claire
Marshfield Medical Center-EC Cancer Center
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org
Marshfield
Marshfield Medical Center-Marshfield
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org
Minocqua
Marshfield Clinic-Minocqua Center
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org
Rice Lake
Marshfield Medical Center-Rice Lake
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org
Stevens Point
Marshfield Medical Center-River Region at Stevens Point
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org
Weston
Marshfield Medical Center - Weston
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org
PRIMARY OBJECTIVE: I. To evaluate the rate of complete minimal residual disease (MRD) response by flow cytometry after 4 weekly doses of daratumumab-hyaluronidase (Day 29) among patients with MRD positive T-cell acute lymphoblastic leukemia (T-ALL) in hematologic morphologic complete remission or complete remission with incomplete hematologic recovery. SECONDARY OBJECTIVES: I. To evaluate morphologic relapse free survival (RFS). II. To evaluate overall survival (OS). III. To assess the survival outcomes in patients that undergo allogeneic stem cell transplant after complete MRD response with daratumumab-hyaluronidase. IV. To assess adverse effects and tolerability of daratumumab-hyaluronidase in T-ALL. IVa. To assess adverse effects of daratumumab-hyaluronidase during Course 1 among all treated patients. IVb. To assess adverse effects of combined daratumumab-hyaluronidase and chemotherapy during Course 1A. IVc. To assess adverse effects of daratumumab-hyaluronidase received during Course 2. V. To assess flow cytometry based MRD status on Day 64 of treatment or upon count recovery for patients that receive chemotherapy in addition to daratumumab-hyaluronidase during Course 1A. VI. To assess MRD response in patients receiving daratumumab-hyaluronidase after first line chemotherapy compared to patients receiving daratumumab-hyaluronidase after second or later lines of chemotherapy. EXPLORATORY OBJECTIVES: I. To determine MRD relapse free survival (RFS) in patients that achieve MRD negative response with daratumumab-hyaluronidase. II. To compare the outcomes of patients with MRD relapse ranging 0.01% to < 0.1% to patients with MRD relapse >= 0.1%. III. To determine the rate of complete molecular MRD response on Day 29 based on Clonal Ig/T-cell receptor (TCR) gene rearrangements using Adaptive clonoSEQ next generation sequencing. IV. To identify molecular abnormalities that are associated with MRD relapse or morphologic relapse. OUTLINE: COURSE 1: Patients receive daratumumab and hyaluronidase-fihj subcutaneously (SC) on days 1, 8, 15, and 22. COURSE 1A: Patients who are MRD positive after Course 1 receive daratumumab and hyaluronidase-fihj SC on days 36, 43, 50, and 57. Patients also receive 1 of 2 methotrexate-based chemotherapy regimens: 1) cytarabine intravenously (IV) on days 37 and 38 and methotrexate IV on day 36; OR 2) methotrexate IV on days 36, 46, and 56, vincristine IV on days 36, 46, and 56, pegaspargase IV on days 37 and 58, and methotrexate intrathecally (IT) on days 36 and 56. COURSE 1B: Patients who are MRD negative after Course 1 may proceed to allogeneic stem cell transplant OR may receive daratumumab and hyaluronidase-fihj SC on days 36, 43, 50, and 57. COURSE 2: Patients who are MRD negative after Course 1A or 1B may proceed to allogeneic stem cell transplant OR may receive daratumumab and hyaluronidase-fihj SC on days 1, 15, 29, 43, 57, 71, 85, and 99. Patients who are MRD positive after Course 1A or 1B discontinue study treatment. After completion of study treatment, patients are followed every 2 months for up to 18 months from start of treatment.
Interactive content above is from the official study record on the National Cancer Institute website, cancer.gov.
The ECOG-ACRIN Cancer Research Group designed this trial and is conducting it with funding from the National Cancer Institute through its National Clinical Trials Network.