LymphomaPhase 1/2NCT04961801
Acalabrutinib for GVHD Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplantation in Lymphomas and Leukemia
A Phase 1/2 study testing Acalabrutinib, tacrolimus, methotrexate in people with Lymphoma and Leukemia, run by Shin Mineishi.
Trial summary
GVHD remains a major cause of morbidity and mortality following SCT. The current standard of care for prophylaxis against GVHD includes tacrolimus and methotrexate. This study proposes to utilize acalabrutinib, a Bruton tyrosine kinase (BTK) inhibitor, for GVHD prophylaxis following allogeneic SCT. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- What is being tested?
- Acalabrutinib, tacrolimus, methotrexate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Mar 2022to Jan 2030
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willingness and ability to sign the study-specific informed consent form
- Willingness to comply with all study procedures and attend all study visits.
- Participant with (a) B-cell malignancies or (b) AML (CD117 positive) who are undergoing allogeneic SCT at Penn State Cancer Institute from an 8/8 matched unrelated donor. Donor selection and screening criteria are to comply with 21 CRF Part 1271.
- Male or female participant, age ≥ 18 and ≤ 75 years.
- Ability to swallow oral medication.
- Women of childbearing potential (WOCP) as defined as not surgically sterile or not postmenopausal must have a negative serum pregnancy test at screening and a negative urine pregnancy test within 7 days of beginning the condition regimen.
- Men and WOCP must agree to use 2 medically accepted method of contraception and must agree to continue use this method while on the trial and through at least one week after the last dose of study drug. Acceptable methods of contraception include abstinence, barrier method with spermicide, intrauterine device (IUD) known to have a failure rate of less than 1% per year, or steroidal contraceptive (oral, transdermal, implanted, or injected) in conjunction with a barrier method. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods) withdrawal, spermicides only, or lactational amenorrhea are not acceptable methods of contraception. WOCP must use a medically accepted method of contraception and must agree to continue use this method from the time of signing the informed consent through at least one week after the last dose of study drug.
- Karnofsky Performance Scale (KPS) equal to or greater than 70%.
Who cannot join
- Renal dysfunction with eGFR <30/mL/minute/1.73 m2 by Cockroft-Gault formula.
- Participant requires warfarin or vitamin K antagonist within one week of acalabrutinib administration.
- Participant requires treatment with a strong cytochrome P450 3A inducer or inhibitor.
- Treatment with post-transplant cyclophosphamide
- Treatment with any other investigational products within 21 days of conditioning regimen.
- Known hypersensitivity to acalabrutinib, tacrolimus and methotrexate and their excipients.
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- Active uncontrolled infections
- Human immunodeficiency virus (HIV) positivity.
- Hepatitis B or C serologic status: subjects who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antigen (HBsAg) negative will need to have a negative polymerase chain reaction (PCR) and must be willing to undergo DNA PCR testing during the study to be eligible. Those who are HBsAg positive or hepatitis B PCR positive will be excluded. Subjects who are hepatitis C antibody positive will need to have a negative PCR result to be eligible. Those who are hepatitis C PCR positive will be excluded.
- Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of study procedures.
- Diagnosed or treated for another malignancy within 2 years before study registration or previously diagnosed with another malignancy and have any evidence of residual disease. Participant with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone resection.
- Participant with coagulopathy or bleeding disorder.
- Known hepatic cirrhosis or severe pre-existing hepatic impairment (ALT and/or AST more than 3x greater than upper limit of normal, Total Bilirubin more than 2x greater than upper limit of normal)
- Uncontrolled high blood pressure (i.e., systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg).
- Uncontrolled or symptomatic cardiac arrhythmia
- Left ventricular ejection fraction (LVEF) < 40% as assessed by echocardiogram or radionuclide angiography, or NYHA class 3 or 4 heart failure
- Myocardial infarction within 6 months of signing consent.
- History of stroke or intracranial hemorrhage within 6 months of signing consent.
- Breastfeeding or pregnant.
- Has difficulty with or is unable to swallow oral medication, or has significant gastrointestinal disease that would limit absorption of oral medication.
- Suspected or confirmed PML(Progressive Multifocal Leukoencephalopathy)
- Requires treatment with proton-pump inhibitors. (Participants receiving proton-pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment.)
- FVC, FEV1, or DLCO (corrected with hemoglobin) less than 40% of expected value.
- Prothrombin time (PT)/INR or aPTT (in the absence of lupus anticoagulant) >2x ULN.
- Major surgical procedure within 28 days of first dose of study drug. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug.
- Concurrent participation in another therapeutic clinical trial.
About this study
GVHD remains a major cause of morbidity and mortality following SCT. The current standard of care for prophylaxis against GVHD includes tacrolimus and methotrexate.
This study proposes to utilize acalabrutinib, a Bruton tyrosine kinase (BTK) inhibitor, for GVHD prophylaxis following allogeneic SCT.
The hypothesis is that the addition of acalabrutinib to our institutional standard GVHD prophylaxis (tacrolimus and methotrexate) is safe, feasible, and effective in reducing both the incidence and severity of acute GVHD.
- Being tested
- Acalabrutinib, tacrolimus, methotrexate
- Keywords
- Graft-Versus-Host Disease Prophylaxis
- Medical subject headings
- Lymphoma, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acalabrutinib, tacrolimus, methotrexateDrug
For Graft-Versus-Host Disease Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplantation in Lymphomas and Leukemia
| Study group | Role | What they receive |
|---|---|---|
| Acalabrutinib in combination with tacrolimus and methotrexate | Experimental | 1. Phase I: To determine the maximum tolerated dose (MTD) of Acalabrutinib in combination with tacrolimus and methotrexate for Phase II.
2. Phase II: To determine if acalabrutinib in combination with tacrolimus and methotrexate is safe and effective in reducing acute GVHD rate. Receives: Drug: Acalabrutinib, tacrolimus, methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity
Dose-limiting toxicity of acalabrutinib in combination with tacrolimus and methotrexate in early SCT for Phase I part of the study
Measured: 30 days
Maximum tolerated dose (MTD)
Maximum tolerated dose (MTD) of acalabrutinib in combination with tacrolimus and methotrexate in early SCT for Phase I part of the study
Measured: 30 days
acute GVHD grade II-IV
Incidence of acute GVHD grade II-IV by day 180 for Phase II part of the study
Measured: 180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2021
- Study startMar 2022 (estimated)
- Primary completionJan 2026 (estimated)
- Study completionJan 2030 (estimated)
Why it stopped: Manufacturer AstraZeneca withdrew the study due to lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shin Mineishi
- Sponsor type
- University, hospital or other
- Collaborators
- Milton S. Hershey Medical Center
- Responsible party
- Sponsor-investigator, Shin Mineishi, Milton S. Hershey Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04961801
- Sponsor's protocol ID
- PSCI-18-128
- Status last verified
- Feb 2022
- First submitted
- 16 Jun 2021
- Last updated
- 8 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acalabrutinib for GVHD Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplantation in Lymphomas and Leukemia
- ClinicalTrials.gov ID
- NCT04961801
- Acronym / sponsor ID
- PSCI-18-128
- Keywords
- Graft-Versus-Host Disease Prophylaxis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Manufacturer AstraZeneca withdrew the study due to lack of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Shin MineishiUniversity, hospital or other
- Collaborators
- Milton S. Hershey Medical Center
- Study start
- Mar 2022 (estimated)
- Primary completion
- Jan 2026 (estimated)
- Study completion
- Jan 2030 (estimated)
- First posted
- 14 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
GVHD remains a major cause of morbidity and mortality following SCT. The current standard of care for prophylaxis against GVHD includes tacrolimus and methotrexate.
This study proposes to utilize acalabrutinib, a Bruton tyrosine kinase (BTK) inhibitor, for GVHD prophylaxis following allogeneic SCT.
The hypothesis is that the addition of acalabrutinib to our institutional standard GVHD prophylaxis (tacrolimus and methotrexate) is safe, feasible, and effective in reducing both the incidence and severity of acute GVHD.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Acalabrutinib in combination with tacrolimus and methotrexate | Experimental | Drug: Acalabrutinib, tacrolimus, methotrexate1. Phase I: To determine the maximum tolerated dose (MTD) of Acalabrutinib in combination with tacrolimus and methotrexate for Phase II. 2. Phase II: To determine if acalabrutinib in combination with tacrolimus and methotrexate is safe and effective in reducing acute GVHD rate. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Willingness and ability to sign the study-specific informed consent form
- Willingness to comply with all study procedures and attend all study visits.
- Participant with (a) B-cell malignancies or (b) AML (CD117 positive) who are undergoing allogeneic SCT at Penn State Cancer Institute from an 8/8 matched unrelated donor. Donor selection and screening criteria are to comply with 21 CRF Part 1271.
- Male or female participant, age ≥ 18 and ≤ 75 years.
- Ability to swallow oral medication.
Key exclusion criteria (26 listed)
- Renal dysfunction with eGFR <30/mL/minute/1.73 m2 by Cockroft-Gault formula.
- Participant requires warfarin or vitamin K antagonist within one week of acalabrutinib administration.
- Participant requires treatment with a strong cytochrome P450 3A inducer or inhibitor.
- Treatment with post-transplant cyclophosphamide
- Treatment with any other investigational products within 21 days of conditioning regimen.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Acalabrutinib, tacrolimus, methotrexateFor Graft-Versus-Host Disease Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplantation in Lymphomas and Leukemia | Drug | Acalabrutinib in combination with tacrolimus and methotrexate |
Primary outcome
Dose-limiting toxicity
Time frame: 30 days
Dose-limiting toxicity of acalabrutinib in combination with tacrolimus and methotrexate in early SCT for Phase I part of the study
Maximum tolerated dose (MTD)
Time frame: 30 days
Maximum tolerated dose (MTD) of acalabrutinib in combination with tacrolimus and methotrexate in early SCT for Phase I part of the study
acute GVHD grade II-IV
Time frame: 180 days
Incidence of acute GVHD grade II-IV by day 180 for Phase II part of the study
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Acalabrutinib, tacrolimus, methotrexate in people with Lymphoma and Leukemia, run by Shin Mineishi.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 8 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-limiting toxicity (time frame: 30 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2022.