Acalabrutinib for Lymphoma

Phase-Based Progress Estimates
1
Effectiveness
1
Safety
Dana-Farber Cancer Institute, Boston, MA
Lymphoma+3 More
Acalabrutinib - Drug
Eligibility
18+
All Sexes
Eligible conditions
Select

Study Summary

Avo In R/R And Previously Untreated MCL

See full description

Eligible Conditions

  • Lymphoma
  • Mantle Cell Lymphoma (MCL)
  • Refractory Lymphomas

Treatment Effectiveness

Effectiveness Estimate

1 of 3

Study Objectives

This trial is evaluating whether Acalabrutinib will improve 2 primary outcomes and 16 secondary outcomes in patients with Lymphoma. Measurement will happen over the course of up to 30 days after the last dose of study treatment or until resolution of toxicity to grade 1 or baseline, whichever occurs last up to 5 years.

10 Months
Rate of therapy discontinuation
5 months
Recommended Phase 2 Dose for acalabrutinib
7 Months
CR rate after 7 cycles cohort A
Complete Remission Rate
Rate of tumor lysis syndrome
7 months
Complete Remission (CR) rate after 7 cycles in the entire study population
Partial Response (PR) Rate after 7 cycles
Progressive Disease Rate after 7 Cycles
Rate of peripheral blood MRD-negativity after 7 cycles
Stable Disease Rate after 7 cycles
Up to 5 Years
Progression Free Survival-Median
Up to 5 years
Overall Survival
Overall Survival-Median
Progression Free Survival
Rate of infusion related reactions
Time to clinical disease progression
Up to 8 months
Time to Minimal Residual Disease (MRD)-positive disease recurrence in the peripheral blood
Year 5
Number of Participants with Treatment Related Adverse Events CTCAE 5.0 criteria

Trial Safety

Safety Estimate

1 of 3

Trial Design

1 Treatment Group

Acalabrutinib, Venetoclax, and Obinutuzumab
1 of 1
Experimental Treatment

This trial requires 41 total participants across 1 different treatment group

This trial involves a single treatment. Acalabrutinib is the primary treatment being studied. Participants will all receive the same treatment. There is no placebo group. The treatments being tested are in Phase 1 & 2 and have already been tested with other people.

Acalabrutinib, Venetoclax, and ObinutuzumabThis study will consist of 2 parts (Parts A and B) and begin in the relapsed/refractory (R/R) MCL setting (Part A) with the phase 1 portion consisting of a dose finding stage to determine the recommended phase 2 dose (RP2D).The phase 1 dose finding stage will follow a 3+3 dose finding schema, such that there will be a safety pause and evaluation after the first 3 participants at any given dose level have completed therapy through cycle 5, day 1. If there are no dose limiting toxicities (DLTs) seen, an additional 3 participants will be treated at the same dose level and if there are 0 or 1 DLTs seen, the RP2D will have been determined. Each study drug is given according to a different schedule. Each treatment cycle lasts 28 days (4 weeks). Acalabrutinib: Obinutuzumab: Venetoclax:
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Acalabrutinib
FDA approved
Venetoclax
FDA approved
Obinutuzumab
FDA approved

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: up to 5 years
This trial has the following approximate timeline: 3 weeks for initial screening, variable treatment timelines, and roughly up to 5 years for reporting.

Closest Location

Dana-Farber Cancer Institute - Boston, MA

Eligibility Criteria

This trial is for patients born any sex aged 18 and older. You must have received 1 prior treatment for Lymphoma or one of the other 3 conditions listed above. There are 10 eligibility criteria to participate in this trial as listed below.

Mark “yes” if the following statements are true for you:
as “pathogenic” People who are participating in part B without prior anti-lymphoma therapy should be considered ineligible for autologous stem cell transplant by the treating physician and/or have a TP53 mutation detected by next generation sequencing at a variant (mutant) allele fraction above the validated threshold for calling a new variant as “pathogenic. show original
Only people who have a molecular marker identified from their peripheral blood will be eligible to participate in part B, which is a study of treatments based on minimal residual disease. show original
Participants in part B who do not have a molecular marker identified by ClonoSEQ from the peripheral blood will be deemed to be MRD indeterminate and are not eligible for peripheral blood MRD driven treatment interruptions show original
Any person with a lymphoma who has a measurable disease mass of 1.5 cm or more in at least one dimension, as determined by a CT scan, PET/CT scan, or MRI scan, will be eligible for the study show original
People in part A, who have had a stem cell transplant and have been treated with CAR T-cells, may have relapsed or not responded to previous treatment. show original
despite ongoing therapy Someone who has B symptoms (fever, drenching night sweats, or unintentional weight loss ≥ 10% body weight over previous 6 months) or functionally significant fatigue despite ongoing therapy is said to have Systemic Lupus Erythematosus. show original
1) A person who has had at least one prior treatment with an anti-CD20 monoclonal antibody, or who has not had previous treatment with any other anti-lymphoma therapy besides corticosteroids or radiotherapy, is considered to be a candidate for treatment with obinutuzumab show original
or medication toxicity (WBC <1.5x109/L; ANC <1.0x109/L, Hgb <10g/dL; platelets <50x109/L) The patient has problems with organ function because of disease or medication, which results in a low white blood cell count, low absolute neutrophil count, low hemoglobin level, and low platelet count. show original
Symptomatic adenopathy or splenomegaly
Local symptoms due to extranodal disease

Patient Q&A Section

What causes lymphoma, mantle-cell?

"A large proportion of lymphomas occur in people who have neoplastic lymphoreticulous cells in their bone marrow, spleen, peripheral blood or lymphoid tissue that can be regarded as precursors of lymphocytes." - Anonymous Online Contributor

Unverified Answer

How many people get lymphoma, mantle-cell a year in the United States?

"The estimates of incidence of lymphoma, in particular, MCL, are of great interest. It seems that the number is decreasing, but it remains unacceptably high, particularly among people under the age of 50 years." - Anonymous Online Contributor

Unverified Answer

What are common treatments for lymphoma, mantle-cell?

"There is no known cure and no specific treatment for mantle-cell lymphoma. This may be due to the large number of lymphomas that have not been studied and [the low survival of this type of lymphoma when it does occur (see overall survival table above)]. As a result, there are few clinical trials with mantle-cell lymphoma. If you are seeking information about lymphoma power makes it easy to find clinical trial options specific to your condition, treatment, and location." - Anonymous Online Contributor

Unverified Answer

What are the signs of lymphoma, mantle-cell?

"Lymphoma can manifest as enlargement of the lymph nodes. Asymmetrical enlargement, which may contain hard tissue, is most often seen. The enlargement may also be more prominent in the neck. Lymphoma can present as a new rash or hair loss. The skin, especially the face, may be flushed in color. The skin may be painful to the touch or to the touch. The scalp may become itchy. Fever is common in lymphoma. Lymphoma can also cause swelling in the abdomen. Symptoms including low white blood count, blood dyscrasias, and low red blood cell level are also seen in the early stages of lymphoma." - Anonymous Online Contributor

Unverified Answer

What is lymphoma, mantle-cell?

"Lymphoma, mantle-cell is a malignant lymphoma involving B-cells with the hallmark features of Hodgkin lymphocytes, follicular dendritic cells and Reed-Sternberg cells. Lymphoma, mantle-cell accounts for about 10% of all non-Hodgkin lymphomas. It frequently involves the liver and, to a lesser extent, the skin, brain and bone marrow. The prognosis is excellent but long-term survival is not exceptional." - Anonymous Online Contributor

Unverified Answer

Can lymphoma, mantle-cell be cured?

"Patients diagnosed with large cell lymphoma (MCL) have a poor prognosis, and, therefore, have been treated primarily through the use of high-dose chemotherapy. We present a case wherein the disease progressed following a brief course of HDC with autologous stem cell transplantation. This patient has relapsed after a subsequent course of HDC/ALLRT chemotherapy. This case highlights the need for a careful assessment of the patient's disease status as part of the therapeutic dilemma that must be resolved when patients are diagnosed with large cell lymphoma." - Anonymous Online Contributor

Unverified Answer

What is acalabrutinib?

"Acalabrutinib is a novel FDA-approved inhibitor of the Bruton's tyrosine kinase (BTK) pathway, which plays a crucial role in the B-cell receptor (BCR) signaling pathway. Thus, acalabrutinib is a promising treatment option for patients with mantle-cell lymphoma (MCL), follicular lymphoma (FL), [b-cell lymphoma] of the diffuse form and for patients resistant to standard immunotherapy." - Anonymous Online Contributor

Unverified Answer

Is acalabrutinib safe for people?

"A substantial proportion of people treated for mantle cell lymphoma with AC will require cessation of the drug due to adverse events (AEs). However, a substantial proportion of the patients will experience a benefit response, allowing them to continue a regimen with an additional benefit while adhering to the recommended dosing intervals, resulting in a manageable risk to benefit ratio." - Anonymous Online Contributor

Unverified Answer

Have there been any new discoveries for treating lymphoma, mantle-cell?

"The development of targeted therapies, combining chemotherapy and antibody and protein-tyrosine kinase inhibitors have improved the outcome of patients with refractory or relapsed mantle-cell lymphoma. A combination of bortezomib with rituximab has been shown to be successful at inducing long-term survivorship in both in vivo and in vivo phase 2 trial studies; however, a phase 3 clinical trial is ongoing. Novel anti-PD-L1 antibodies, tislelizumab and nivolumab, have shown very good evidence of response in mantle-cell lymphoma on preclinical studies; however, there is insufficient data to date to support their introduction in the clinic." - Anonymous Online Contributor

Unverified Answer

What are the chances of developing lymphoma, mantle-cell?

"Only a very small number of patients develop SLL, mantle-cell lymphoma, or peripheral T-cell lymphoma. Of these patients, the risk was significantly higher after the diagnosis of SLL. Lymphoid follicular and non-Hodgkin's lymphomas are the most common types. The incidence of T-cell lymphoma was extremely low, and the long-term prognosis was good in most patients: no deaths due to complications were recorded in patients with newly detected disease. The risk of lymphoma development in the general population is low and does not seem to depend on age." - Anonymous Online Contributor

Unverified Answer

What are the common side effects of acalabrutinib?

"Acalabrutinib is well tolerated in patients with mantle cell lymphoma. Common somatic adverse events with acalabrutinib included headache, nausea, gastrointestinal adverse events (e.g., nausea, vomiting, anorexia, dyspepsia), and fatigue. Severe adverse events were rare." - Anonymous Online Contributor

Unverified Answer

How serious can lymphoma, mantle-cell be?

"Patients with lymphoma have a 10 percent mortality rate 5 years after diagnosis. Survival is improved if diagnosis is made early and if lymphoma is treated with less-intensive chemotherapy regimens." - Anonymous Online Contributor

Unverified Answer
Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.
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