A Phase III Randomized Trial of Steroids + Tyrosine Kinase Inhibitor (TKI) Induction With Chemotherapy or Blinatumomab for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia (ALL) in Adults
| Registry | NCT04530565 |
|---|---|
| Status | Active not recruiting |
| Phase | Phase 3 |
| Study type | Interventional; randomized, crossover, masking: none, treatment |
| Enrollment | 348 (Estimated) |
| Sponsor | National Cancer Institute (NCI) (Nih) |
| Conditions | B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 |
| Interventions | Biospecimen Collection, Blinatumomab, Bone Marrow Aspiration and Biopsy, Cyclophosphamide, Cytarabine, Dasatinib, Dexamethasone, Doxorubicin Hydrochloride, Echocardiography Test, Electrocardiography, Lumbar Puncture, Mesna, Methotrexate, Multigated Acquisition Scan, Ponatinib Hydrochloride, Prednisone, Vincristine Sulfate (Procedure, biological, drug) |
| Dates | start 2021-01-25, primary completion 2028-07-01 (estimated), completion 2028-07-01 (estimated), first posted 2020-08-28, last updated 2026-08-28 |
| Locations | 211 sites in United States, Israel, Puerto Rico |
Related Papers Related Patents Related Grants Related Experts
All trials for B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 All trials of Biospecimen Collection All trials of Blinatumomab
This phase III trial compares the effect of usual treatment of chemotherapy and steroids and a tyrosine kinase inhibitor (TKI) to the same treatment plus blinatumomab. Blinatumomab is a Bi-specific T-Cell Engager ('BiTE') that may interfere with the ability of cancer cells to grow and spread. The information gained from this study may help researchers determine if combination therapy with steroids, TKIs, and blinatumomab work better than the standard of care.
PRIMARY OBJECTIVE:
I. To compare the overall survival (OS) following induction with steroids + TKI + blinatumomab versus induction with steroids + TKI + chemotherapy.
SECONDARY OBJECTIVES:
I. To compare the rate of minimal residual disease (MRD) negative complete remission (CR) for patients treated with chemotherapy versus (vs) blinatumomab at the end of first induction (week 15).
II. To evaluate the rate of the MRD negative CR by treatment arm for those patients MRD positive after the first induction and administered of second induction.
III. To compare event free survival (EFS) for patients initially randomized for chemotherapy vs blinatumomab.
IV. To assess the toxicities of blinatumomab + TKI vs. TKI + chemotherapy in this patient population.
V. To assess the toxicities of the chemotherapy regimen in this patient population.
VI. To describe the outcome of patients who proceed to allogeneic stem cell transplant after treatment with blinatumomab + TKI only.
OUTLINE:
ARM A (PRE-INDUCTION): Patients receive prednisone orally (PO) once daily (QD) on days 1-21 and ponatinib hydrochloride (ponatinib) PO QD or dasatinib PO QD on days 1-21 based on investigator's choice.
Patients are randomized to 1 of 2 arms (Arm B or C). Patients undergo bone marrow aspiration with biopsy, lumbar punctures, echocardiogram (ECHO), and multigated acquisition (MUGA) scans as indicated by investigator.
ARM B (INDUCTION THERAPY):
CYCLE 1: Patients receive cyclophosphamide intravenously (IV) twice daily (BID) on days 1-3, dexamethasone PO or IV on days 1-4 and 11-14, cytarabine intrathecally (IT) on day 1, doxorubicin hydrochloride (doxorubicin) IV on day 4, vincristine sulfate (vincristine) IV on days 4 and 11, and methotrexate IT on day 8. Patients also receive Mesna 600mg/m\^2 IV as a 'chemoprotectant' via continuous infusion on days 1-3, (beginning 1 hour prior to cyclophosphamide and completed by 12 hours after the last dose of cyclophosphamide).
CYCLE 2 (AGE 18-70): Starting in cycle 2, fit patients aged 18-70 receive dasatinib 70mg/day PO QD or ponatinib 30mg/day PO QD on days 1-21, methotrexate IV over 24 hours and IT on day 1, and cytarabine IV over 2 hours BID on days 2-3 of each cycle. On day 22 of cycle 2 or later, as soon as the absolute neutrophil count (ANC) is greater than 1000 cells/ul and platelets are greater than 50,000 cells/ul, patients receive hyper cyclophosphamide, vincristine, doxorubicin, and dexamethasone (CVAD) for 2 additional cycles.
CYCLE 2 (AGE > 70 or unfit < 70): Starting in cycle 2, patients age > 70 or younger unfit patients for Hyper-CVAD receive ponatinib PO QD or dasatinib PO QD on days 1-21 of each cycle. Patients also receive methotrexate IV over 24 hours and IT on day 1, and cytarabine IV over 2 hours BID on days 2-3 of each cycle. Cycle 1 and 2 regimens are each repeated once starting on day 22 of cycle 2, or later, but as soon as the ANC is greater than 1000 cells/ul and platelets are greater than 50,000 cells/ul.
Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve remission (significant reduction in the amount of leukemia in bone marrow and blood/MRD negative) after 4 cycles may receive alternative treatment, either consolidation with two cycles of Hyper-CVAD followed by TKI maintenance therapy or undergo allogeneic stem cell transplantation followed by maintenance therapy. Patients who do not achieve a remission (MRD positive) are assigned to Arm D. Patients who experience un-resolving renal failure or life-threatening infection which may require a treatment delay of 21 days cross-over to Arm C to receive the prescribed course of blinatumomab.
ARM C (INDUCTION THERAPY):
CYCLE 1: Patients receive ponatinib PO QD or dasatinib PO QD on days 1-28. Patients also receive dexamethasone PO or IV on day 1 and blinatumomab IV continuously on days 1-28, followed by methotrexate IT on day 29 or 30.
CYCLE 2: Patients receive ponatinib PO QD or dasatinib PO QD on days 1-28. Patients also receive dexamethasone PO or IV on day 1 and blinatumomab IV continuously on days 1-28, followed by methotrexate IT on day 29 or 30.
Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
ARM D (RE-INDUCTION): Patients treated on Arm B who remain MRD positive at the end of induction therapy receive blinatumomab based re-induction identical to the regimen described for Arm C.
ARM E (RE-INDUCTION): Patients treated on Arm C who remain MRD positive at the end of induction therapy receive chemotherapy based re-induction which is identical to regimen described for Arm B according to patient's age and the pre-specified chemotherapy arm.
Patients whose molecular test remains MRD positive after re-induction proceed to follow-up at the discretion of the investigator or receive anti CD-19 CAR- T cell therapy, inotuzumab ozogamicin, intensive chemotherapy, or palliative care.
Patients are followed up every 3 months for first 2 years (from study registration), every 6 months for years 3-5, and then every 12 months for years 6-10.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Arm A (steroid, TKI), Single Arm Pre-Induction | Active comparator | Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration and Biopsy; Drug: Dasatinib; Procedure: Echocardiography Test; Procedure: Electrocardiography; Procedure: Lumbar Puncture; Procedure: Multigated Acquisition Scan; Drug: Ponatinib Hydrochloride; Drug: Prednisone | Patients receive prednisone PO QD on days 1-21 and ponatinib PO QD or dasatinib PO QD on days 1-21 based on investigator's choice. |
| Arm B (steroid, TKI, chemotherapy) | Experimental | Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration and Biopsy; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dasatinib; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Procedure: Echocardiography Test; Procedure: Electrocardiography; Procedure: Lumbar Puncture; Drug: Mesna; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Ponatinib Hydrochloride; Drug: Vincristine Sulfate | See Detailed Description. |
| Arm C (steroid, TKI, chemotherapy, immunotherapy) | Experimental | Procedure: Biospecimen Collection; Biological: Blinatumomab; Procedure: Bone Marrow Aspiration and Biopsy; Drug: Dasatinib; Drug: Dexamethasone; Procedure: Echocardiography Test; Procedure: Electrocardiography; Procedure: Lumbar Puncture; Drug: Mesna; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Ponatinib Hydrochloride | CYCLE 1: Patients receive ponatinib PO QD or dasatinib PO QD on days 1-28. Patients also receive dexamethasone PO or IV on day 1 and blinatumomab IV continuously on days 1-28, followed by methotrexate IT on day 29 or 30. CYCLE 2: Patients receive ponatinib PO QD or dasatinib PO QD on days 1-28. Patients also receive dexamethasone PO or IV on day 1 and blinatumomab IV continuously on days 1-28, followed by methotrexate IT on day 29 or 30. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. |
| Arm D (steroid, TKI, chemotherapy, immunotherapy) | Experimental | Procedure: Biospecimen Collection; Biological: Blinatumomab; Procedure: Bone Marrow Aspiration and Biopsy; Drug: Cyclophosphamide; Drug: Dasatinib; Drug: Dexamethasone; Procedure: Echocardiography Test; Procedure: Electrocardiography; Procedure: Lumbar Puncture; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Ponatinib Hydrochloride | Patients treated on Arm B who remain MRD positive at the end of induction therapy receive blinatumomab based re-induction identical to the regimen described for Arm C. Patients whose molecular test remains MRD positive after re-induction proceed to follow-up at the discretion of the investigator or receive anti CD-19 CAR- T cell therapy, inotuzumab ozogamicin, intensive chemotherapy, or palliative care. |
| Arm E (steroid, TKI, chemotherapy) | Experimental | Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration and Biopsy; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dasatinib; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Procedure: Echocardiography Test; Procedure: Electrocardiography; Procedure: Lumbar Puncture; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Ponatinib Hydrochloride; Drug: Vincristine Sulfate | Patients treated on Arm C who remain MRD positive at the end of induction therapy receive chemotherapy based re-induction which is identical to regimen described for Arm B according to patient's age and the pre-specified chemotherapy arm. Patients whose molecular test remains MRD positive after re-induction proceed to follow-up at the discretion of the investigator or receive anti CD-19 CAR- T cell therapy, inotuzumab ozogamicin, intensive chemotherapy, or palliative care. |
Sex: All, ages: 18 Years to 75 Years
Inclusion Criteria:
* ELIGIBILITY CRITERIA FOR PRE-REGISTRATION (TO STEP 0)
* Patient must be >= 18 and =< 75 years of age
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status between 0-3
* Patient must be newly diagnosed with B acute lymphoblastic leukemia (B-ALL) or is suspected to have acute lymphoblastic leukemia (ALL)
* Patient must have BCR-ABL1 positive disease. The diagnosis of ALL and the presence of BCR-ABL translocation must be confirmed centrally. Patients can be registered and begin step 1 therapy while awaiting central laboratory eligibility confirmation
* NOTE: Bone marrow aspirate and/or peripheral blood specimen must be submitted to the ECOG-American College of Radiology Imaging Network (ACRIN) Leukemia Laboratory at MD Anderson Cancer Center to determine patient's eligibility for registration to Step 1 or confirm patient evaluability. Centrally fluorescence-activated cell sorting (FACS) analysis will be performed to determine B-ALL and to exclude acute myeloid leukemia (AML) or acute bi-phenotypic leukemia and baseline BCR-ABL status will be determined by fluorescent in situ hybridization (FISH). The ECOG-ACRIN Leukemia Laboratory will forward results within 48 hours of receipt of the specimen to the submitting institution. Bone marrow aspirate is to be from first pull (initial or re-direct). Specimens must contain sufficient blast cells. In cases where the bone marrow aspiration may be inadequate, or the bone marrow examination has already been performed prior to study consent and enrollment on Step 0, peripheral blood may be submitted, with recommendation that adequate circulating blasts are present (> 10%). If a diagnosis of BCR-ABL positive B-ALL has already been established by local Clinical Laboratory Improvement Act (CLIA) certified laboratories, the patient may be registered to step 1 without waiting for central confirmation
* Patient must not have a diagnosis of BCR/ABL T-ALL
* Patient must not have received chemotherapy for B-ALL. Patients who received up to five days of therapy (hydroxyurea and/or steroids of any kind) with the aim to reduce disease burden prior to study registration to Step 1 are eligible
* Patient must not have unstable epilepsy that requires treatment
* Patients with lymphoid blast crisis chronic myeloid leukemia (CML) are not eligible
* ELIGIBILITY CRITERIA FOR REGISTRATION TO STEP 1
* Patient must have a diagnosis of Philadelphia chromosome positive (Ph+) ALL that has been determined locally and bone marrow and/or peripheral blood was sent and receipt confirmed for central confirmation or determined centrally by the ECOG-ACRIN Leukemia Laboratory at MD Anderson Cancer Center
* 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 registration to rule out pregnancy. A patient of childbearing potential is defined as any woman, regardless of 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 accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of step 1 registration, while on study treatment, and until at least six months after the last dose of study treatment
* Total bilirubin =< 3 mg/dL (patients with Gilbert's syndrome must have a total bilirubin =< 5 mg/dL) (obtained =< 28 days prior to step 1 registration)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =< 2.5 X the institutional upper limit of normal (ULN) (obtained =< 28 days prior to step 1 registration)
* Estimated creatinine clearance > 45 mL/min (based on Cockcroft-Gault equation) (obtained =< 28 days prior to step 1 registration)
* Patients with acute organ dysfunction at step 1 registration, which may be attributed to leukemia can be registered regardless of lab results at presentation. Such patients will be allowed to register and can start Arm A steroid + TKI therapy but will only be allowed to proceed to step 2 randomization if the eligibility criteria outlined is met
* Patients who presented with no evidence of acute organ dysfunction but during step 0 experienced a rise in liver enzymes which investigator suspects to be a side effect of any of prescribed drugs, are allowed to be registered regardless of the level of liver enzymes. Step 2 randomization must be withheld until the eligibility criteria outline is met but no more than 14 days after concluding Arm A therapy
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable or on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have an undetectable HCV viral load and if indicated, on treatment
* Patients with a prior 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
* Patient must not have active concomitant malignancy. Patients on chronic hormonal therapy for breast or prostate cancer or patients treated with maintenance with targeted agents but are in remission with no evidence for the primary malignancies are eligible
* Patient must not have complaints of symptoms and/or have clinical and/or radiological signs that indicate an uncontrolled infection or any other concurrent medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol
* 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 must be class 2B or better
* Investigators must confirm which TKI patient is to receive
* NOTE: Patients with known T315I mutation status should receive ponatinib treatment
* NOTE: In situations due to insurance coverage issues and the pre-selected TKI is not immediately available, patients can receive dasatinib or imatinib during step 1. The investigator must re-specify dasatinib or ponatinib prior to step 2 randomization and from then on patients must receive the pre-selected TKI only
* ELIGIBILITY CRITERIA FOR RANDOMIZATION TO STEP 2
* Patient must have completed at least 7 and no more than 21 days of protocol-treatment on Arm A prior to step 2 randomization. (Days in which arm A therapy was withheld for any reason are not counted)
* NOTE: First day of steroids prescription after registration will be considered as the first day of study therapy. The selected TKI must be initiated prior to randomization
* Patients who presented with acute organ dysfunction within 2 weeks of registration to step 1 must have total bilirubin =< 2 X institutional upper limit of normal (ULN)
* AST(SGOT) and ALT(SGPT) =< 2 X the institutional upper limit of normal (ULN)
* Estimated creatinine clearance > 45 mL/min (based on Cockcroft-Gault equation)
* Investigators must confirm which TKI patient is to receive.
* NOTE: Patients with known T315I mutation status should receive ponatinib treatment
* For patients under age 70, intended chemotherapy regimen must have been determined prior to randomization
* Patient must not have active central nervous system (CNS) involvement by leukemic blasts. Patients with signs of CNS involvement at presentation are eligible for randomization if clearance of blasts from the cerebrospinal fluid (CSF) is demonstrated
* Patients must have resolved any serious infectious complications related to therapy
* Any significant medical complications related to therapy must have resolved
* ELIGIBILITY CRITERIA FOR REGISTRATION TO STEP 3 (RE-INDUCTION)
* Institution has received centralized MRD results confirming positive status
* Patients who presented with acute organ dysfunction within 2 weeks of registration to step 1 must have total bilirubin =< 2 X institutional ULN
* Patients who presented with acute organ dysfunction must have AST (SGOT)/ALT (SGPT) =< 2 X institutional upper limit of normal (ULN)
* Patients who presented with acute organ dysfunction must have an estimated creatinine clearance > 45 mL/min (based on Cockcroft-Gault equation)
* Investigators must confirm which TKI patient is to receive
* NOTE: Patients with known T315I mutation status should receive ponatinib treatment
* For patients under age 70 and previously assigned to Arm C, intended chemotherapy regimen must have been determined
* Step 3 (Re-Induction): Patients must have resolved any serious infectious complications related to therapy
* Step 3 (Re-Induction): Any significant medical complications related to therapy must have resolved| Facility | City | Country | Status |
|---|---|---|---|
| University of Alabama at Birmingham Cancer Center | Birmingham, Alabama | United States | |
| Anchorage Associates in Radiation Medicine | Anchorage, Alaska | United States | |
| Anchorage Radiation Therapy Center | Anchorage, Alaska | United States | |
| Alaska Breast Care and Surgery LLC | Anchorage, Alaska | United States | |
| Alaska Oncology and Hematology LLC | Anchorage, Alaska | United States | |
| Alaska Women's Cancer Care | Anchorage, Alaska | United States | |
| Anchorage Oncology Centre | Anchorage, Alaska | United States | |
| Katmai Oncology Group | Anchorage, Alaska | United States | |
| Providence Alaska Medical Center | Anchorage, Alaska | United States | |
| Mercy Hospital Fort Smith | Fort Smith, Arkansas | United States | |
| Providence Saint Joseph Medical Center/Disney Family Cancer Center | Burbank, California | United States | |
| Community Cancer Institute | Clovis, California | United States | |
| University Oncology Associates | Clovis, California | United States | |
| City of Hope Comprehensive Cancer Center | Duarte, California | United States | |
| UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care | Irvine, California | United States | |
| UC San Diego Moores Cancer Center | La Jolla, California | United States | |
| UC Irvine Health/Chao Family Comprehensive Cancer Center | Orange, California | United States | |
| Yale University | New Haven, Connecticut | United States | |
| Augusta University Medical Center | Augusta, Georgia | United States | |
| Hawaii Cancer Care Inc - Waterfront Plaza | Honolulu, Hawaii | United States | |
| Queen's Cancer Cenrer - POB I | Honolulu, Hawaii | United States | |
| Queen's Medical Center | Honolulu, Hawaii | United States | |
| Straub Clinic and Hospital | Honolulu, Hawaii | United States | |
| University of Hawaii Cancer Center | Honolulu, Hawaii | United States | |
| Hawaii Cancer Care Inc-Liliha | Honolulu, Hawaii | United States | |
| Kuakini Medical Center | Honolulu, Hawaii | United States | |
| Queen's Cancer Center - Kuakini | Honolulu, Hawaii | United States | |
| The Cancer Center of Hawaii-Liliha | Honolulu, Hawaii | United States | |
| Kapiolani Medical Center for Women and Children | Honolulu, Hawaii | United States | |
| Wilcox Memorial Hospital and Kauai Medical Clinic | Lihue, Hawaii | United States | |
| Hawaii Cancer Care - Westridge | ‘Aiea, Hawaii | United States | |
| Pali Momi Medical Center | ‘Aiea, Hawaii | United States | |
| Queen's Cancer Center - Pearlridge | ‘Aiea, Hawaii | United States | |
| The Cancer Center of Hawaii-Pali Momi | ‘Aiea, Hawaii | United States | |
| Saint Luke's Cancer Institute - Boise | Boise, Idaho | United States | |
| Saint Luke's Cancer Institute - Fruitland | Fruitland, Idaho | United States | |
| Saint Luke's Cancer Institute - Meridian | Meridian, Idaho | United States | |
| Saint Alphonsus Cancer Care Center-Nampa | Nampa, Idaho | United States | |
| Saint Luke's Cancer Institute - Nampa | Nampa, Idaho | United States | |
| Saint Luke's Cancer Institute - Twin Falls | Twin Falls, Idaho | United States | |
| OSF Saint Anthony's Health Center | Alton, Illinois | United States | |
| Loyola Center for Health at Burr Ridge | Burr Ridge, Illinois | United States | |
| Northwestern University | Chicago, Illinois | United States | |
| NorthShore University HealthSystem-Evanston Hospital | Evanston, Illinois | United States | |
| NorthShore University HealthSystem-Glenbrook Hospital | Glenview, Illinois | United States | |
| NorthShore University HealthSystem-Highland Park Hospital | Highland Park, Illinois | United States | |
| Loyola Medicine Homer Glen | Homer Glen, Illinois | United States | |
| Northwestern Medicine Lake Forest Hospital | Lake Forest, Illinois | United States | |
| Loyola University Medical Center | Maywood, Illinois | United States | |
| Marjorie Weinberg Cancer Center at Loyola-Gottlieb | Melrose Park, Illinois | United States | |
| SSM Health Good Samaritan | Mount Vernon, Illinois | United States | |
| Indiana University/Melvin and Bren Simon Cancer Center | Indianapolis, Indiana | United States | |
| Mary Greeley Medical Center | Ames, Iowa | United States | |
| McFarland Clinic - Ames | Ames, Iowa | United States | |
| McFarland Clinic - Boone | Boone, Iowa | United States | |
| McFarland Clinic - Trinity Cancer Center | Fort Dodge, Iowa | United States | |
| McFarland Clinic - Jefferson | Jefferson, Iowa | United States | |
| McFarland Clinic - Marshalltown | Marshalltown, Iowa | United States | |
| Central Care Cancer Center - Garden City | Garden City, Kansas | United States | |
| Central Care Cancer Center - Great Bend | Great Bend, Kansas | United States | |
| University of Kansas Cancer Center | Kansas City, Kansas | United States | |
| University of Kansas Hospital-Indian Creek Campus | Overland Park, Kansas | United States | |
| University of Kansas Hospital-Westwood Cancer Center | Westwood, Kansas | United States | |
| The James Graham Brown Cancer Center at University of Louisville | Louisville, Kentucky | United States | |
| UofL Health Medical Center Northeast | Louisville, Kentucky | United States | |
| LSU Health Sciences Center at Shreveport | Shreveport, Louisiana | United States | |
| Johns Hopkins University/Sidney Kimmel Cancer Center | Baltimore, Maryland | United States | |
| Walter Reed National Military Medical Center | Bethesda, Maryland | United States | |
| Trinity Health Saint Joseph Mercy Hospital Ann Arbor | Ann Arbor, Michigan | United States | |
| University of Michigan Rogel Cancer Center | Ann Arbor, Michigan | United States | |
| Trinity Health IHA Medical Group Hematology Oncology - Brighton | Brighton, Michigan | United States | |
| Trinity Health Medical Center - Brighton | Brighton, Michigan | United States | |
| Henry Ford Cancer Institute-Downriver | Brownstown, Michigan | United States | |
| Trinity Health IHA Medical Group Hematology Oncology - Canton | Canton, Michigan | United States | |
| Trinity Health Medical Center - Canton | Canton, Michigan | United States | |
| Chelsea Hospital | Chelsea, Michigan | United States | |
| Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital | Chelsea, Michigan | United States | |
| Hematology Oncology Consultants-Clarkston | Clarkston, Michigan | United States | |
| Newland Medical Associates-Clarkston | Clarkston, Michigan | United States | |
| Henry Ford Macomb Hospital-Clinton Township | Clinton Township, Michigan | United States | |
| Henry Ford Medical Center-Fairlane | Dearborn, Michigan | United States | |
| Wayne State University/Karmanos Cancer Institute | Detroit, Michigan | United States | |
| Henry Ford Hospital | Detroit, Michigan | United States | |
| Weisberg Cancer Treatment Center | Farmington Hills, Michigan | United States | |
| Cancer Hematology Centers - Flint | Flint, Michigan | United States | |
| Genesee Hematology Oncology PC | Flint, Michigan | United States | |
| Genesys Hurley Cancer Institute | Flint, Michigan | United States | |
| Hurley Medical Center | Flint, Michigan | United States | |
| Allegiance Health | Jackson, Michigan | United States | |
| Trinity Health Saint Mary Mercy Livonia Hospital | Livonia, Michigan | United States | |
| Henry Ford Saint John Hospital - Macomb Medical | Macomb, Michigan | United States | |
| Henry Ford Medical Center-Columbus | Novi, Michigan | United States | |
| Michigan Healthcare Professionals Pontiac | Pontiac, Michigan | United States | |
| Newland Medical Associates-Pontiac | Pontiac, Michigan | United States | |
| Trinity Health Saint Joseph Mercy Oakland Hospital | Pontiac, Michigan | United States | |
| MyMichigan Medical Center Saginaw | Saginaw, Michigan | United States | |
| Oncology Hematology Associates of Saginaw Valley PC | Saginaw, Michigan | United States | |
| Henry Ford Macomb Health Center - Shelby Township | Shelby, Michigan | United States | |
| MyMichigan Medical Center Tawas | Tawas City, Michigan | United States | |
| Henry Ford West Bloomfield Hospital | West Bloomfield, Michigan | United States |
111 more sites not listed.
NIH grants: U10CA180820