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New treatment option for Recurrent Mantle Cell Lymphoma
Official title Modified Immune Cells (CD19 CAR T Cells) and Acalabrutinib for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma
ClinicalTrials.gov ID: NCT04484012
What this study is testing
What is Acalabrutinib?
Acalabrutinib is an investigational medicine, given as an once-daily infusion into a vein, being studied as a potential treatment for recurrent mantle cell lymphoma.
Also referred to as ACP-196, Bruton Tyrosine Kinase Inhibitor ACP-196.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This phase II trial investigates the side effects of CD19 chimeric antigen receptor (CAR) T cells and acalabrutinib, and to see how well they work in treating patients with mantle cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). T cells are infection fighting blood cells that can kill cancer cells.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 to 75
You may be able to join if
- Informed Consent and Willingness to Participate
- All participants must have the ability to understand and the willingness to sign a written informed consent.
- Participants must agree to allow the use of archival tissue from diagnostic tumor biopsies.
- If unavailable, exceptions may be granted with Study PI approval. Note: For research participants who do not speak English, a short form consent may...
- Age 18 years and older. Performance Status
You likely can't join if
- Previous therapies
- Allogeneic hematopoietic cell transplantation (HCT) within the last 6 months.
- Autologous HCT within the last 3 months.
- Prior failure of any BTK inhibitor therapy. (Participant WILL be allowed if, after administration of other BTK inhibitors they have switched to...
- Participants known to have mutations associated with resistance to BTK inhibitors from prior studies. Concomitant therapies
- Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary...
See the full eligibility criteria
Who can join
- Informed Consent and Willingness to Participate
- All participants must have the ability to understand and the willingness to sign a written informed consent.
- Participants must agree to allow the use of archival tissue from diagnostic tumor biopsies.
- If unavailable, exceptions may be granted with Study PI approval. Note: For research participants who do not speak English, a short form consent may be used with a COH certified interpreter/translator to proceed with...
- Age 18 years and older. Performance Status
- ECOG Performance status ≤ 2 or KPS ≥ 70% (Appendix A) Nature of Illness and Treatment-Related Criteria
- Documented CD19+ MCL by flow cytometry or IHC (from biopsy) if prior CD19 directed therapy was previously used a. BM is optional at enrollment IF patient already has biopsy proven disease.
- Participants must be currently receiving acalabrutinib and have been taking acalabrutinib for between 3 and 7 months prior to initiating screening procedures on the study and:
- must have at least 1 prior regimen (not including single-agent corticosteroids)
- best response to acalabrutinib therapy is MRD+ CR, PR or SD at the time of screening b (1) must have measurable disease by CT scan (≥ 1.5 cm) or evidence of blood, spleen, skin, gastrointestinal (GI) or bone marrow...
- No contraindications to leukapheresis, steroids or tocilizumab Clinical Laboratory Criteria (To be performed within 28 days prior to enrollment)
- Total serum bilirubin ≤ 2.0 mg/dL Participants with Gilbert syndrome may be included if their total bilirubin is ≥ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN.
- Blood counts:
- Absolute Neutrophil count (ANC ≥1000 cells/ul)\
- Growth factor use within 7 days prior screening is not allowed
- Platelet count ≥75,000/ul. Transfusion with 7 days prior to screening is not allowed\ \ Exception: participants with bone marrow involvement do not need to meet this criteria
- AST \< 3 x ULN
- ALT \< 3 x ULN
- Creatinine clearance of ≥ 50 mL/min per the Cockcroft-Gault formula
- International Normalized Ratio (INR) OR Prothrombin (PT) ≤ 1.5 x ULN
- Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN
- Female of childbearing potential: negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Cardiac function (12 lead-ECG): QTc must be ≤ 480 msec
- Left ventricular ejection fraction \>40%
- Oxygen saturation 92% or above at room air or DLCO of 40% of best predicted Contraception
- Participants of reproductive potential must agree to use highly effective birth control methods throughout therapy and for 2 months after final CAR T cell infusion and/or 2 days after final acalabrutinib dose, whichever...
What rules you out
- Previous therapies
- Allogeneic hematopoietic cell transplantation (HCT) within the last 6 months.
- Autologous HCT within the last 3 months.
- Prior failure of any BTK inhibitor therapy. (Participant WILL be allowed if, after administration of other BTK inhibitors they have switched to acalabrutinib prior to lymphodepletion, and if the duration of all BTK...
- Participants known to have mutations associated with resistance to BTK inhibitors from prior studies. Concomitant therapies
- Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. Physiologic replacement of steroids (i.e., prednisone ≤ 7.5 mg /day, or...
- Approved anti-cancer therapies other than acalabrutinib are not allowed after enrollment, with the exception of steroids or involved field radiation to control progressive disease during cell manufacturing, prior to...
- Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer.
- Unable to discontinue anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) within 7 days of leukapheresis and remain off through end of study treatment. Other illnesses or conditions
- Class III/IV cardiovascular disability according to the New York Heart Association Classification. people with controlled, asymptomatic atrial fibrillation can enroll.
- Participants with clinically significant arrhythmia or arrhythmias not stable on medical management.
- Active auto-immune disease requiring systemic immunosuppressive therapy, including uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP).
- Suspected or confirmed progressive multifocal leukoencephalopathy (PML).
- Requires major surgical procedure within 28 days prior to first dose of study drug. If a subject has major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before...
- Participants with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system.
- Known history of drug-specific hypersensitivity or anaphylaxis to either study agent.
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or...
- Known bleeding disorders (e.g., von Willebrand's disease or hemophilia)
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
- History of other malignancies, except for the following: malignancy surgically resected (or treated with other modalities) with curative intent, adequately treated in situ carcinoma of the breast or cervix uteri, basal...
- Lactating women.
- Active chronic graft-versus-host disease (GVHD) post-allogeneic HCT.
- Uncontrolled active infection:
- HIV positive or have active hepatitis B or C infection based on testing performed within 4 weeks of enrollment.
- Hepatitis B or C serologic status: people who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR) result. Those who are...
- people who are hepatitis B core antibody positive (or have a known history of HBV infection) should be monitored quarterly with a quantitative PCR test for HBV DNA. HBV monitoring should last until 12 months after last...
- people who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded.
- people who are positive cytomegalovirus [CMV] DNA polymerase chain reaction [PCR]).
- Subject with any active significant bacterial, fungal or viral (other than those listed) infections.
- Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures. Noncompliance
- Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).
- Eligibility should be confirmed per institutional policies.
The study team makes the final eligibility decision.
Where it's taking place
- Duarte, California, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years to 75 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Duarte, California, United States. Enter your location above to see the nearest site and check your eligibility.
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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.