New combo therapy aims to outperform standard drugs for rare blood cancer
NCT ID NCT04840602
First seen Jun 25, 2026 · Last updated Jul 30, 2026 · Updated 8 times
Summary
This phase II trial is testing whether a combination of venetoclax and rituximab works better than current standard treatments (ibrutinib plus rituximab or zanubrutinib alone) for people with previously untreated Waldenstrom's macroglobulinemia, a rare type of blood cancer. The study will enroll 92 participants and measure how well the cancer responds to treatment. The goal is to find a more effective first-line therapy that can improve outcomes for patients.
What this could mean
Our plain-language read of the trial. This is informational only, not medical advice or a prediction.
- Active substance
- Venetoclax, rituximab, ibrutinib, zanubrutinib
- What this could lead to
- If successful, this trial could identify a more effective first-line treatment for Waldenstrom's macroglobulinemia, potentially improving response rates and delaying disease progression.
- What could go wrong
- This is a phase II trial with only 92 participants, so results are preliminary. The experimental combination may not prove superior to existing treatments, and side effects from these drugs can include infections, bleeding, and heart issues.
This is an AI summary of the original study and may miss details. Read our disclaimer.
Study facts
What this study's own registry entry says, in plain language.
- Phase
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Phase 2
Tests whether the treatment actually works, and watches for side effects, in a larger group.
- Participants
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About 92 people
The number the study aims to enrol. It can still change while the study runs.
- Started
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Jan 2022
- Expected to finish
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Mar 2028
An estimate. End dates often move.
- Lead sponsor
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A government research agency
The lead sponsor is the US National Institutes of Health.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
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18 years and older
- Sex
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Anyone
- Healthy volunteers
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Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
Inclusion Criteria: * Participants must have had a confirmed diagnosis of Waldenstrom's macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL). Participants must have measurable disease as determined by IgM protein quantification. * IgM Spike: ≥ 500 mg/dL (≥ 5 g/L) * Extramedullary disease: The manifestation of a lymphoid mass outside of the bone marrow, resulting in enlargement in extramedullary organs such as the lymph nodes or spleen. Note: all participants must have measurable IgM spike, but are not required to have extramedullary disease * Testing to establish baseline disease status must be performed within 28 days prior to registration * Participants must have at least one of the criteria to require therapy for WM including: * Anemia * Thrombocytopenia * Neuropathy related to WM * Symptomatic hyperviscosity or serum viscosity levels ≥ 4.0 centipoises * WM associated glomerulonephritis or renal disease, bulky disease, or constitutional symptoms * Constitutional symptoms can be described as: * Unintentional weight loss \>= 10% within the previous 6 months prior to screening * Fevers higher than 100.5 degrees Fahrenheit (F) or 38.0 degrees Celsius (C) for 2 or more weeks prior to screening without evidence of infection * Night sweats for more than 1 month prior to screening without evidence of infection * Clinically relevant fatigue which is not relieved by rest due to WM * Participants who require ongoing use or received a moderate or strong CYP3A inducer, moderate or strong CYP3A inhibitor, P-gp inhibitor within 7 days prior to the first dose of study drug will be excluded from the study. If such participants can be safely switched to an alternative agent, then the participants will be eligible to enroll * Participants must not have had prior systemic therapy. Prior therapy with rituximab will be allowed as long as the last rituximab dose was at least 6 months prior to registration * Participants must be \>= 18 years of age * Participants must have history and physical exam within 28 days prior to registration * Participants must have Zubrod performance status =\< 2 * Participants must have evidence of adequate renal function, as defined by creatinine clearance (CrCl) \>= 30 mL/min. Values must be obtained within 14 days prior to registration * Total bilirubin =\< 1.5 x IULN (institutional upper limit of the norm) (within 14 days prior to registration) * Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =\< 3 x IULN (within 14 days prior to registration) * Alkaline phosphatase =\< 3 x IULN (within 14 days prior to registration) * Platelet count \>= 50,000 cells/mm\^3 (within 14 days prior to registration) * NOTE: Transfusion and/or growth factor support is allowed up to 7 days prior to registration * Hemoglobin \>= 7.0 g/dL (within 14 days prior to registration) * NOTE: Transfusion and/or growth factor support is allowed up to 7 days prior to registration * Absolute neutrophil count (ANC) \>= 1,000 cells/mm\^3 (within 14 days prior to registration) * NOTE: Transfusion and/or growth factor support is allowed up to 7 days prior to registration * Participants with known human immunodeficiency virus (HIV)-infection are eligible providing they are on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test and within 6 months prior to registration * Participants must be able to take and swallow oral medication (capsules) whole. Participants may not have any known impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) * Participants must not be intolerant to rituximab * Participants must not have known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding localized skin and nail bed fungal infections) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) 4 weeks prior to registration * Participants 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). Hepatitis C virus (HCV) testing is only required if clinically indicated or if the participant has a history of HCV * Participants must not consume grapefruit, Seville oranges or starfruit within 3 days prior to the first dose of venetoclax * Participants must not be pregnant or nursing because venetoclax has not been studied in pregnant or nursing women and the mechanism of action is expected to cause fetal harm. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" e.g., implants, injectables, combined oral contraceptives, some intrauterine devices \[IUDs\], complete abstinence, or sterilized partner) and a barrier method (e.g., condom, cervical ring, sponge, etc.). This also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate participant chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures throughout the study and for at least 30 days after competition of therapy * 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 participant is currently in complete remission, or any other cancer from which the participant has been disease free for two years or watchful waiting is appropriate in the opinion of the treating physician. Also, malignancy that in the opinion of the investigator, is considered cured with minimal risk of recurrence within 5 years, is permissible consideration of eligibility for this trial * Participants must be offered the opportunity to participate in specimen banking * Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines. For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations * As a part of the Oncology Participant Enrollment Network (OPEN) registration process 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 * CROSSOVER CRITERIA: Participants must have been registered and received treatment in the IR/Z or VR arm and must show progression of disease at any time during cycles 3-24 * CROSSOVER CRITERIA: In case of transformation to intermediate or high-grade lymphoma or development of Bing-Neel syndrome the participants will not undergo registration step 2 crossover and will be taken off the study * CROSSOVER CRITERIA: Participants must have Zubrod performance status =\< 2 * CROSSOVER CRITERIA: Participants must have evidence of adequate renal function, as defined by creatinine clearance (CrCl) \>= 30 mL/min. Values must be obtained within 14 days prior to registration * CROSSOVER CRITERIA: Participants must have no evidence of marked hepatic dysfunction on any recent liver function tests within 14 days prior to registration * CROSSOVER CRITERIA: Platelet count \>= 50,000 cells/mm\^3 (without within 14 days prior to registration) * NOTE: Transfusion and/or growth factor support is allowed up to 7 days prior to registration * CROSSOVER CRITERIA: Hemoglobin \>= 7.0 g/dL (without within 14 days prior to registration) * NOTE: Transfusion and/or growth factor support is allowed up to 7 days prior to registration * CROSSOVER CRITERIA: Absolute neutrophil count (ANC) \>= 1,000 cells/mm\^3 (without within 14 days prior to registration) * NOTE: Transfusion and/or growth factor support is allowed up to 7 days prior to registration
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Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
How to take part
Only the study team decides who joins. These are the ways to reach them.
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The study's own enquiry address
This study publishes an address for enquiries. See it below .
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The places running it
127 sites. The list below names each one and where it is.
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The official record
ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.
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A doctor treating you
A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.
Contacts and locations
Show contact details
Enter your email to view the contact information for this study.
By submitting, you agree to our Terms of use
Locations
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Abbott-Northwestern Hospital
RECRUITINGMinneapolis, Minnesota, 55407, United States
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Adena Regional Medical Center
SUSPENDEDChillicothe, Ohio, 45601, United States
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Atrium Health Union/LCI-Union
RECRUITINGMonroe, North Carolina, 28112, United States
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Banner University Medical Center - Tucson
RECRUITINGTucson, Arizona, 85719, United States
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Cancer Care Center of O'Fallon
RECRUITINGO'Fallon, Illinois, 62269, United States
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Cancer Care Specialists of Illinois - Decatur
RECRUITINGDecatur, Illinois, 62526, United States
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Cancer Hematology Centers - Flint
RECRUITINGFlint, Michigan, 48503, United States
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Carle Cancer Center
RECRUITINGUrbana, Illinois, 61801, United States
Contact Email: •••••@•••••
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Carle Physician Group-Effingham
RECRUITINGEffingham, Illinois, 62401, United States
Contact Email: •••••@•••••
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Carle Physician Group-Mattoon/Charleston
RECRUITINGMattoon, Illinois, 61938, United States
Contact Email: •••••@•••••
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Carle at The Riverfront
RECRUITINGDanville, Illinois, 61832, United States
Contact Email: •••••@•••••
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Carolinas Medical Center/Levine Cancer Institute
RECRUITINGCharlotte, North Carolina, 28203, United States
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Central Ohio Breast and Endocrine Surgery
SUSPENDEDGahanna, Ohio, 43230, United States
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Centralia Oncology Clinic
RECRUITINGCentralia, Illinois, 62801, United States
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Chelsea Hospital
RECRUITINGChelsea, Michigan, 48118, United States
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City of Hope at Irvine Lennar
RECRUITINGIrvine, California, 92618, United States
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Columbus Oncology and Hematology Associates Inc
SUSPENDEDColumbus, Ohio, 43214, United States
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Crossroads Cancer Center
RECRUITINGEffingham, Illinois, 62401, United States
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Delaware Health Center-Grady Cancer Center
SUSPENDEDDelaware, Ohio, 43015, United States
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Doctors Hospital
SUSPENDEDColumbus, Ohio, 43228, United States
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Dublin Methodist Hospital
SUSPENDEDDublin, Ohio, 43016, United States
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Fairfield Medical Center
SUSPENDEDLancaster, Ohio, 43130, United States
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Genesee Hematology Oncology PC
SUSPENDEDFlint, Michigan, 48503, United States
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Genesis Healthcare System Cancer Care Center
SUSPENDEDZanesville, Ohio, 43701, United States
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Genesys Hurley Cancer Institute
RECRUITINGFlint, Michigan, 48503, United States
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Glens Falls Hospital
ACTIVE_NOT_RECRUITINGGlens Falls, New York, 12801, United States
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Grady Memorial Hospital
SUSPENDEDDelaware, Ohio, 43015, United States
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Grant Medical Center
SUSPENDEDColumbus, Ohio, 43215, United States
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Gundersen Lutheran Medical Center
RECRUITINGLa Crosse, Wisconsin, 54601, United States
Contact Email: •••••@•••••
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Heartland Regional Medical Center
RECRUITINGSaint Joseph, Missouri, 64506, United States
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Hematology Oncology Consultants-Clarkston
RECRUITINGClarkston, Michigan, 48346, United States
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Hennepin County Medical Center
RECRUITINGMinneapolis, Minnesota, 55415, United States
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Henry Ford Hospital
RECRUITINGDetroit, Michigan, 48202, United States
Contact Email: •••••@•••••
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Henry Ford Macomb Hospital-Clinton Township
RECRUITINGClinton Township, Michigan, 48038, United States
Contact Email: •••••@•••••
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Henry Ford Medical Center-Columbus
RECRUITINGNovi, Michigan, 48377, United States
Contact Email: •••••@•••••
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Henry Ford West Bloomfield Hospital
RECRUITINGWest Bloomfield, Michigan, 48322, United States
Contact Email: •••••@•••••
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Hurley Medical Center
RECRUITINGFlint, Michigan, 48503, United States
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Huron Gastroenterology PC
RECRUITINGYpsilanti, Michigan, 48106, United States
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Knox Community Hospital
SUSPENDEDMount Vernon, Ohio, 43050, United States
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Levine Cancer Institute-Gaston
RECRUITINGGastonia, North Carolina, 28054, United States
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Licking Memorial Hospital
RECRUITINGNewark, Ohio, 43055, United States
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Loyola University Medical Center
RECRUITINGMaywood, Illinois, 60153, United States
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Marietta Memorial Hospital
SUSPENDEDMarietta, Ohio, 45750, United States
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Marshfield Medical Center - Minocqua
ACTIVE_NOT_RECRUITINGMinocqua, Wisconsin, 54548, United States
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Marshfield Medical Center - Weston
RECRUITINGWeston, Wisconsin, 54476, United States
Contact Email: •••••@•••••
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Marshfield Medical Center-EC Cancer Center
ACTIVE_NOT_RECRUITINGEau Claire, Wisconsin, 54701, United States
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Marshfield Medical Center-Marshfield
ACTIVE_NOT_RECRUITINGMarshfield, Wisconsin, 54449, United States
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Marshfield Medical Center-Rice Lake
ACTIVE_NOT_RECRUITINGRice Lake, Wisconsin, 54868, United States
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Marshfield Medical Center-River Region at Stevens Point
RECRUITINGStevens Point, Wisconsin, 54482, United States
Contact Email: •••••@•••••
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Mary Greeley Medical Center
RECRUITINGAmes, Iowa, 50010, United States
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Mayo Clinic in Florida
RECRUITINGJacksonville, Florida, 32224-9980, United States
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Mayo Clinic in Rochester
RECRUITINGRochester, Minnesota, 55905, United States
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McFarland Clinic - Ames
RECRUITINGAmes, Iowa, 50010, United States
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McFarland Clinic - Boone
SUSPENDEDBoone, Iowa, 50036, United States
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McFarland Clinic - Jefferson
SUSPENDEDJefferson, Iowa, 50129, United States
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McFarland Clinic - Marshalltown
RECRUITINGMarshalltown, Iowa, 50158, United States
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McFarland Clinic - Trinity Cancer Center
RECRUITINGFort Dodge, Iowa, 50501, United States
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Memorial Sloan Kettering Basking Ridge
RECRUITINGBasking Ridge, New Jersey, 07920, United States
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Memorial Sloan Kettering Bergen
RECRUITINGMontvale, New Jersey, 07645, United States
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Memorial Sloan Kettering Cancer Center
RECRUITINGNew York, New York, 10065, United States
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Memorial Sloan Kettering Commack
RECRUITINGCommack, New York, 11725, United States
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Memorial Sloan Kettering Monmouth
RECRUITINGMiddletown, New Jersey, 07748, United States
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Memorial Sloan Kettering Nassau
RECRUITINGUniondale, New York, 11553, United States
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Memorial Sloan Kettering Westchester
RECRUITINGHarrison, New York, 10604, United States
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Mercy Health - Perrysburg Hospital
SUSPENDEDPerrysburg, Ohio, 43551, United States
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Mercy Health - Saint Anne Hospital
SUSPENDEDToledo, Ohio, 43623, United States
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Mercy Health - Saint Vincent Hospital
SUSPENDEDToledo, Ohio, 43608, United States
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Mercy Hospital
RECRUITINGCoon Rapids, Minnesota, 55433, United States
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Mercy Hospital South
RECRUITINGSt Louis, Missouri, 63128, United States
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Michigan Healthcare Professionals Pontiac
RECRUITINGPontiac, Michigan, 48341, United States
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Mount Carmel East Hospital
SUSPENDEDColumbus, Ohio, 43213, United States
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Mount Carmel Grove City Hospital
SUSPENDEDGrove City, Ohio, 43123, United States
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Mount Carmel Health Center West
SUSPENDEDColumbus, Ohio, 43222, United States
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MyMichigan Medical Center Saginaw
RECRUITINGSaginaw, Michigan, 48601, United States
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MyMichigan Medical Center Tawas
RECRUITINGTawas City, Michigan, 48764, United States
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NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
ACTIVE_NOT_RECRUITINGNew York, New York, 10032, United States
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Newark Radiation Oncology
SUSPENDEDNewark, Ohio, 43055, United States
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Newland Medical Associates-Clarkston
SUSPENDEDClarkston, Michigan, 48346, United States
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Newland Medical Associates-Pontiac
RECRUITINGPontiac, Michigan, 48341, United States
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OhioHealth Mansfield Hospital
SUSPENDEDMansfield, Ohio, 44903, United States
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OhioHealth Marion General Hospital
SUSPENDEDMarion, Ohio, 43302, United States
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Oncology Hematology Associates of Saginaw Valley PC
SUSPENDEDSaginaw, Michigan, 48604, United States
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Park Nicollet Clinic - Saint Louis Park
RECRUITINGSaint Louis Park, Minnesota, 55416, United States
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Providence Cancer Institute Clackamas Clinic
SUSPENDEDClackamas, Oregon, 97015, United States
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Providence Newberg Medical Center
RECRUITINGNewberg, Oregon, 97132, United States
Contact Email: •••••@•••••
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Providence Portland Medical Center
RECRUITINGPortland, Oregon, 97213, United States
Contact Email: •••••@•••••
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Providence Saint Vincent Medical Center
RECRUITINGPortland, Oregon, 97225, United States
Contact Email: •••••@•••••
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Providence Willamette Falls Medical Center
RECRUITINGOregon City, Oregon, 97045, United States
Contact Email: •••••@•••••
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Regions Hospital
RECRUITINGSaint Paul, Minnesota, 55101, United States
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Riverside Methodist Hospital
SUSPENDEDColumbus, Ohio, 43214, United States
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Saint Alphonsus Cancer Care Center-Nampa
RECRUITINGNampa, Idaho, 83687, United States
Contact Email: •••••@•••••
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Saint Ann's Hospital
SUSPENDEDWesterville, Ohio, 43081, United States
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Saint Francis Medical Center
RECRUITINGCape Girardeau, Missouri, 63703, United States
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Saint Rita's Medical Center
SUSPENDEDLima, Ohio, 45801, United States
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Saint Vincent Frontier Cancer Center
RECRUITINGBillings, Montana, 59102, United States
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Siteman Cancer Center at Christian Hospital
ACTIVE_NOT_RECRUITINGSt Louis, Missouri, 63136, United States
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Siteman Cancer Center at Saint Peters Hospital
ACTIVE_NOT_RECRUITINGCity of Saint Peters, Missouri, 63376, United States
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Siteman Cancer Center at West County Hospital
ACTIVE_NOT_RECRUITINGCreve Coeur, Missouri, 63141, United States
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Siteman Cancer Center-South County
ACTIVE_NOT_RECRUITINGSt Louis, Missouri, 63129, United States
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Southeastern Medical Oncology Center-Clinton
RECRUITINGClinton, North Carolina, 28328, United States
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Southeastern Medical Oncology Center-Goldsboro
RECRUITINGGoldsboro, North Carolina, 27534, United States
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Southeastern Medical Oncology Center-Jacksonville
RECRUITINGJacksonville, North Carolina, 28546, United States
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Southern Illinois University School of Medicine
RECRUITINGSpringfield, Illinois, 62702, United States
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Southern Ohio Medical Center
SUSPENDEDPortsmouth, Ohio, 45662, United States
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Springfield Clinic
RECRUITINGSpringfield, Illinois, 62702, United States
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Springfield Memorial Hospital
RECRUITINGSpringfield, Illinois, 62781, United States
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Strecker Cancer Center-Belpre
SUSPENDEDBelpre, Ohio, 45714, United States
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Swedish Cancer Institute-Edmonds
RECRUITINGEdmonds, Washington, 98026, United States
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Swedish Cancer Institute-Issaquah
RECRUITINGIssaquah, Washington, 98029, United States
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Swedish Medical Center-First Hill
RECRUITINGSeattle, Washington, 98122, United States
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The Mark H Zangmeister Center
SUSPENDEDColumbus, Ohio, 43219, United States
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ThedaCare Regional Cancer Center
RECRUITINGAppleton, Wisconsin, 54911, United States
Contact Email: •••••@•••••
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Trinity Health IHA Medical Group Hematology Oncology - Brighton
RECRUITINGBrighton, Michigan, 48114, United States
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Trinity Health IHA Medical Group Hematology Oncology - Canton
RECRUITINGCanton, Michigan, 48188, United States
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Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
RECRUITINGChelsea, Michigan, 48118, United States
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Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
RECRUITINGYpsilanti, Michigan, 48197, United States
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Trinity Health Medical Center - Brighton
RECRUITINGBrighton, Michigan, 48114, United States
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Trinity Health Medical Center - Canton
RECRUITINGCanton, Michigan, 48188, United States
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Trinity Health Saint Joseph Mercy Hospital Ann Arbor
RECRUITINGAnn Arbor, Michigan, 48106, United States
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Trinity Health Saint Joseph Mercy Oakland Hospital
RECRUITINGPontiac, Michigan, 48341, United States
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Trinity Health Saint Mary Mercy Livonia Hospital
RECRUITINGLivonia, Michigan, 48154, United States
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UM Sylvester Comprehensive Cancer Center at Coral Gables
RECRUITINGCoral Gables, Florida, 33146, United States
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UM Sylvester Comprehensive Cancer Center at Coral Springs
RECRUITINGCoral Springs, Florida, 33065, United States
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UM Sylvester Comprehensive Cancer Center at Deerfield Beach
RECRUITINGDeerfield Beach, Florida, 33442, United States
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UM Sylvester Comprehensive Cancer Center at Doral
RECRUITINGDoral, Florida, 33166, United States
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UM Sylvester Comprehensive Cancer Center at Hollywood
RECRUITINGHollywood, Florida, 33021, United States
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UM Sylvester Comprehensive Cancer Center at Kendall
RECRUITINGMiami, Florida, 33176, United States
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UM Sylvester Comprehensive Cancer Center at Plantation
RECRUITINGPlantation, Florida, 33324, United States
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United Hospital
RECRUITINGSaint Paul, Minnesota, 55102, United States
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University of Arizona Cancer Center-North Campus
RECRUITINGTucson, Arizona, 85719, United States
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University of Miami Miller School of Medicine-Sylvester Cancer Center
RECRUITINGMiami, Florida, 33136, United States
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University of Miami Sylvester Comprehensive Cancer Center at Sole Mia
RECRUITINGNorth Miami, Florida, 33181, United States
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University of Michigan Health - Sparrow Lansing
RECRUITINGLansing, Michigan, 48912, United States
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University of Rochester
RECRUITINGRochester, New York, 14642, United States
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VCU Massey Comprehensive Cancer Center
RECRUITINGRichmond, Virginia, 23298, United States
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Washington University School of Medicine
ACTIVE_NOT_RECRUITINGSt Louis, Missouri, 63110, United States
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Wayne State University/Karmanos Cancer Institute
RECRUITINGDetroit, Michigan, 48201, United States
Contact Email: •••••@•••••
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Weisberg Cancer Treatment Center
RECRUITINGFarmington Hills, Michigan, 48334, United States
Contact Email: •••••@•••••
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