A Phase 2 interventional study of Ibrutinib and Daratumumab in Waldenstrom Macroglobulinemia, Waldenstrom's Disease and Waldenström; Hypergammaglobulinemia, sponsored by Weill Medical College of Cornell University. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-10-23.
Sponsored by Weill Medical College of Cornell University · Phase 2, Interventional, and Treatment
This study evaluates the safety and efficacy of daratumumab in combination with ibrutinib in patients with Waldenstrӧm's macroglobulinemia (WM). The study will evaluate this combination in two cohorts. Cohort A will comprise of ibrutinib naïve WM patients. Patients in this cohort may be treatment naïve or relapsed but who remain ibrutinib naïve. Cohort B will comprise of patients who are currently receiving ibrutinib but whose response to treatment has plateaued. In this cohort, daratumumab will be added on to ibrutinib in an attempt to deepen response.
This is a multi-center, two cohort Phase 2 clinical trial investigating the effectiveness of adding daratumumab to ibrutinib in WM patients. Cohort A will consist of patients who are ibrutinib naïve and appropriate for ibrutinib based treatment. Cohort B will consist of patients who have achieved a response plateau less than a complete remission (CR) on single agent ibrutinib. Subjects in Cohort A will be identified by their treating physician and eligible for enrollment if they are treatment naïve or relapsed after 1 prior therapy for WM and eligible for ibrutinib based treatment.
Subjects in Cohort B will be identified by their treating physician and eligible for enrollment if they have had at least 6 months of exposure to single agent ibrutinib and demonstrate an IgM response plateau defined by two IgM measurements, at least 8 weeks apart that have changed \<15% from the previous mark. In Cohort B response assessment will be measured from initial IgM level prior to ibrutinib initiation.
Enrolled subjects will be prescribed commercial ibrutinib, 420mg PO daily. The investigational agent, daratumumab will be administered based on FDA approved dosing in multiple myeloma (16mg/kg) with 8 weekly induction treatments during Cycles 1 and 2, followed by every other week dosing for Cycles 3-6, then monthly dosing from Cycle 7 until Cycle 25 at which point subjects will continue with ibrutinib as monotherapy until Cycle 52 (4 years total) which is the predefined study completion for enrolled subjects at which point they will complete follow-up. Study visits and response assessments with IgM measurements will occur with each cycle for the first year then every three cycles after cycle 13. Subjects with measureable extramedullary disease will have CT scans every 6 cycles until radiographic CR. Patients will be considered evaluable for response if they completed the initial 8 weeks of daratumumab induction therapy and evaluable for toxicity if receiving one dose of daratumumab. Patients will continue on combination therapy for 2 years or until disease progression or unacceptable toxicities at which point subjects will come off trial. Patients achieving a CR after two years of combination therapy will be given an option to continue with single agent commercial ibrutinib.
524 studies on the registry are indexed under Waldenstrom Macroglobulinemia; 62 are open to participants now.
This study's enrollment of 1 is below the median of 39 across 429 interventional studies indexed under Waldenstrom Macroglobulinemia.
Browse Waldenstrom Macroglobulinemia studies →Weill Medical College of Cornell University is the lead sponsor of 892 studies on the registry; 165 are open to participants now.
Of its 123 completed or terminated interventional studies of FDA-regulated products, 94 (76%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Ibrutinib naïve or previously treated patients currently on ibrutinib with a plateau in disease response are eligible to participate.
Hematology values must be within the following limits:
Biochemical values within the following limits:
d. (ALT) and aspartate aminotransferase (AST) ≤ 3 x (ULN)
e. Total ≤ 2 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin
f. (CLcr) > 25 ml/min
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Washout period
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
COPD
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
FEV1
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cohort A will consist of subjects who are ibrutinib naïve and appropriate for ibrutinib based treatment. Treatment naïve subjects will be eligible to enroll in this cohort. All subjects in this cohort will receive ibrutinib plus daratumumab
Drug: Ibrutinib · Drug: Daratumumab
Cohort B will consist of subjects who have had at least 6 months of exposure to single agent ibrutinib and who have demonstrated an IgM response plateau defined by two IgM measurements, at least 8 weeks apart that have changed \<15% from the previous mark. All subjects in this cohort will receive ibrutinib plus daratumumab
Drug: Ibrutinib · Drug: Daratumumab
Ibrutinib, 420mg orally, once daily
Also known as: IMBRUVICA
Daratumumab, 16 mg/kg intravenously, weekly for 8 weeks, bi weekly for 16 weeks, then monthly for up to 19 months.
Also known as: DARZALEX
Safety of Combination Treatment With Ibrutinib and Daratumumab as Measured by the Number of Patients That Experience 1 or More Adverse Event
Number of patients that experience 1 or more adverse event
Time frame: 3 months
Major Response Rate in Cohort A
Number of patients in Cohort A who achieve VGPR, PR, or CR
Time frame: 5 years
Deepening of Response Rate in Cohort B After Daratumumab Addition
Number of patients in Cohort B who achieve a VGPR, PR, or CR from baseline IgM prior to ibrutinib
Time frame: 5 years
Duration of Response
Measured from time of first response to progression or death, measured in months.
Time frame: 5 years
Time to Progression
Measured from time of study drug administration to progression, measured in months.
Time frame: 5 years
Progression Free Survival
Measured from time of study drug administration to progression or death, measured in months.
Time frame: 3 months
Overall Survival
Measured from time of study drug administration to death, measured in months.
Time frame: 3 months
| Milestone | Cohort A - Ibrutinib Naive | Cohort B - Ibrutinib Response Plateau |
|---|---|---|
| Started | 1 | 0 |
| Completed | 0 | 0 |
| Not completed | 1 | 0 |
| Withdrew: Adverse event | 1 | 0 |
Number of patients that experience 1 or more adverse event
| Participants | Cohort A - Ibrutinib Naive | Cohort B - Ibrutinib Response Plateau |
|---|---|---|
| Safety of Combination Treatment With Ibrutinib and Daratumumab as Measured by the Number of Patients That Experience 1 or More Adverse Event | 1 | — |
Number of patients in Cohort A who achieve VGPR, PR, or CR
No measurements were reported for this outcome.
Number of patients in Cohort B who achieve a VGPR, PR, or CR from baseline IgM prior to ibrutinib
No measurements were reported for this outcome.
Measured from time of first response to progression or death, measured in months.
No measurements were reported for this outcome.
Measured from time of study drug administration to progression, measured in months.
No measurements were reported for this outcome.
Measured from time of study drug administration to progression or death, measured in months.
| months | Cohort A - Ibrutinib Naive | Cohort B - Ibrutinib Response Plateau |
|---|---|---|
| Progression Free Survival | NA | — |
Measured from time of study drug administration to death, measured in months.
| months | Cohort A - Ibrutinib Naive | Cohort B - Ibrutinib Response Plateau |
|---|---|---|
| Overall Survival | NA | — |
Collected over 3 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cohort A - Ibrutinib Naive | 0/1 (0%) | 1/1 (100%) | 1/1 (100%) |
| Cohort B - Ibrutinib Response Plateau | — | — | — |
| Event | Cohort A - Ibrutinib Naive | Cohort B - Ibrutinib Response Plateau |
|---|---|---|
| Elevated ALT/ASTGeneral disorders | 1/1 | — |
| Event | Cohort A - Ibrutinib Naive | Cohort B - Ibrutinib Response Plateau |
|---|---|---|
| VomitingMetabolism and nutrition disorders | 1/1 | — |
| DiarrheaGastrointestinal disorders | 1/1 | — |
| Infusion relatedInjury, poisoning and procedural complications | 1/1 | — |
| Scratchy ThroatRespiratory, thoracic and mediastinal disorders | 1/1 | — |
| ALT increasedInvestigations | 1/1 | — |
| AST increasedInvestigations | 1/1 | — |
| Abdominal PainGastrointestinal disorders | 1/1 | — |
| Malaise- flu like symptomsGeneral disorders | 1/1 | — |
0 subjects were enrolled in Cohort B.
| Age, Categorical(Participants) | Cohort A - Ibrutinib Naive | Cohort B - Ibrutinib Response Plateau | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 1 | 0 | 1 |
| >=65 years | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Cohort A - Ibrutinib Naive | Cohort B - Ibrutinib Response Plateau | Total |
|---|---|---|---|
| Female | 1 | — | 1 |
| Male | 0 | — | 0 |
| Ethnicity (NIH/OMB)(Participants) | Cohort A - Ibrutinib Naive | Cohort B - Ibrutinib Response Plateau | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | — | 0 |
| Not Hispanic or Latino | 1 | — | 1 |
| Unknown or Not Reported | 0 | — | 0 |
| Race (NIH/OMB)(Participants) | Cohort A - Ibrutinib Naive | Cohort B - Ibrutinib Response Plateau | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | — | 0 |
| Asian | 0 | — | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | — | 0 |
| Black or African American | 0 | — | 0 |
| White | 1 | — | 1 |
| More than one race | 0 | — | 0 |
| Unknown or Not Reported | 0 | — | 0 |
| Region of Enrollment(participants) | Cohort A - Ibrutinib Naive | Cohort B - Ibrutinib Response Plateau | Total |
|---|---|---|---|
| United States | 1 | — | 1 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
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Studies of the drugs tested here: Ibrutinib · Daratumumab
Waldenstrom Macroglobulinemia →
Weill Medical College of Cornell University →