ADCT-602 for B-Cell ALL
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: M.D. Anderson Cancer Center
No Placebo Group
Trial Summary
What is the purpose of this trial?This phase I/II trial studies the side effects and best dose of ADCT-602 in treating patients with B-cell lymphoblastic leukemia that has come back or does not respond to treatment. Monoclonal antibodies, such as ADCT-602, may interfere with the ability of tumor cells to grow and spread.
Will I have to stop taking my current medications?
The trial requires that certain medications be stopped before starting the study. Specifically, any chemotherapy, systemic therapy (except for some like steroids and hydroxyurea), or radiotherapy should be stopped at least 14 days before starting the trial. Some maintenance treatments like mercaptopurine, oral methotrexate, vincristine, and tyrosine kinase inhibitors should be stopped at least 48 hours before the study begins.
What data supports the effectiveness of the drug ADCT-602 for B-Cell ALL?
Research shows that epratuzumab, a component of ADCT-602, has been effective in increasing remission rates in patients with relapsed acute lymphoblastic leukemia (ALL) when added to chemotherapy. In one study, the response rate increased from 17% to 52% with the addition of epratuzumab, suggesting it may enhance the effectiveness of treatment for B-Cell ALL.
12345What makes the drug ADCT-602 unique for treating B-Cell ALL?
ADCT-602 is unique because it combines epratuzumab, a monoclonal antibody that targets CD22 on B-cells, with a potent drug that can kill cancer cells. This approach specifically targets and disrupts B-cell function, potentially leading to better outcomes in B-Cell ALL compared to traditional chemotherapy alone.
13467Eligibility Criteria
This trial is for patients with B-cell acute lymphoblastic leukemia that has returned or isn't responding to treatment. Eligible participants must have a certain level of marrow blast count, normal liver and heart function, not be pregnant or breastfeeding, agree to use effective contraception, and cannot have had a recent transplant or other cancer treatments.Inclusion Criteria
I am able to care for myself and perform daily activities.
I am not pregnant and agree to use effective birth control during and after the treatment.
I am a woman who could potentially become pregnant.
My liver enzymes are within the normal range, or up to 5 times the normal limit if cancer has spread to my liver or bones.
My cancer cells show a high level of CD22.
Exclusion Criteria
I am experiencing complications from a transplant.
I do not have any untreated or uncontrolled infections.
I am unable to give consent for this study by myself.
I have a history of or currently have VOD.
I do not have severe heart, lung, or diabetes issues.
My cancer has returned in a specific area outside of the bone marrow.
I have Burkitt's leukemia/lymphoma.
Participant Groups
The trial is testing ADCT-602, a monoclonal antibody designed to stop tumor cells from growing and spreading in patients with recurrent or refractory B-cell acute lymphoblastic leukemia. It's looking at the best dose and side effects.
1Treatment groups
Experimental Treatment
Group I: ADCT-602Experimental Treatment1 Intervention
Patients receive ADCT-602 by vein over 30 minutes on day 1. Courses repeat every 21 in the absence of disease progression or unacceptable toxicity. Patients who achieve CR/CRi receive ADCT-602 every 28 days.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
M D Anderson Cancer CenterHouston, TX
City of Hope Comprehensive CancerMonrovia, CA
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Who is running the clinical trial?
M.D. Anderson Cancer CenterLead Sponsor
National Cancer Institute (NCI)Collaborator
ADC Therapeutics S.A.Industry Sponsor
References
SWOG S0910: a phase 2 trial of clofarabine/cytarabine/epratuzumab for relapsed/refractory acute lymphocytic leukaemia. [2021]Precursor B-acute lymphoblastic leukaemias (pre-B ALLs) comprise the majority of ALLs and virtually all blasts express CD22 in the cytoplasm and on the cell surface. In the present study (Southwestern Oncology Group S0910), we evaluated the addition of epratuzumab, a humanized monoclonal antibody against CD22, to the combination of clofarabine and cytarabine in adults with relapsed/refractory pre-B ALL. The response rate [complete remission and complete remission with incomplete count recovery] was 52%, significantly higher than our previous trial with clofarabine/cytarabine alone, where the response rate was 17%. This result is encouraging and suggests a potential benefit to adding epratuzumab to chemotherapy for ALL; however, a randomized trial will be needed to answer this question.
Re-induction chemoimmunotherapy with epratuzumab in relapsed acute lymphoblastic leukemia (ALL): Phase II results from Children's Oncology Group (COG) study ADVL04P2. [2018]Given the success of immunotherapeutic approaches in hematologic malignancies, the COG designed a phase I/II study to determine whether the addition of epratuzumab (anti-CD22) to an established chemotherapy platform improves rates of second remission (CR2) in pediatric patients with B-lymphoblastic leukemia (B-ALL) and early bone marrow relapse.
Chemoimmunotherapy reinduction with epratuzumab in children with acute lymphoblastic leukemia in marrow relapse: a Children's Oncology Group Pilot Study. [2021]To determine the tolerability and serum concentration of epratuzumab, a humanized monoclonal antibody targeting CD22, administered alone and in combination with reinduction chemotherapy in children with relapsed acute lymphoblastic leukemia (ALL), and to preliminarily assess tumor targeting and efficacy.
The mechanistic impact of CD22 engagement with epratuzumab on B cell function: Implications for the treatment of systemic lupus erythematosus. [2018]Epratuzumab is a B-cell-directed non-depleting monoclonal antibody that targets CD22. It is currently being evaluated in two phase 3 clinical trials in patients with systemic lupus erythematosus (SLE), a disease associated with abnormalities in B-cell function and activation. The mechanism of action of epratuzumab involves perturbation of the B-cell receptor (BCR) signalling complex and intensification of the normal inhibitory role of CD22 on the BCR, leading to reduced signalling and diminished activation of B cells. Such effects may result from down-modulation of CD22 upon binding by epratuzumab, as well as decreased expression of other proteins involved in amplifying BCR signalling capability, notably CD19. The net result is blunting the capacity of antigen engagement to induce B-cell activation. The functional consequences of epratuzumab binding to CD22 include diminished B-cell proliferation, effects on adhesion molecule expression, and B-cell migration, as well as reduced production of pro-inflammatory cytokines, such as IL-6 and TNF. Studies in patients treated with epratuzumab have revealed a number of pharmacodynamic effects that are linked to the mechanism of action (i.e., a loss of the target molecule CD22 from the B-cell surface followed by a modest reduction in peripheral B-cell numbers after prolonged therapy). Together, these data indicate that epratuzumab therapy affords a unique means to modulate BCR complex expression and signalling.
BCR-ABL1 molecular remission after 90Y-epratuzumab tetraxetan radioimmunotherapy in CD22+ Ph+ B-ALL: proof of principle. [2017]Although targeted therapies are used increasingly in hematologic malignancies, we are unaware of any prior studies of radioimmunotherapy (RAIT) in B-acute lymphoblastic leukemia (ALL), even though this radiosensitive tumor expresses CD22, potentially a good target for this approach. Here, we report a patient with Philadelphia chromosome-positive B-ALL in third relapse who received RAIT with (90) yttrium ((90) Y)-labeled anti-CD22 epratuzumab tetraxetan. Seven weeks after initiating therapy, the patient achieved a BCR-ABL1 molecular remission documented by RT-qPCR, which is now continuing at 6 months while awaiting an allogeneic hematopoietic stem cell transplant. (90) Y-Epratuzumab tetraxetan may be a promising therapeutic option for CD22(+) B-ALL patients.
A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma. [2020]ADCT-402 (loncastuximab tesirine) is an antibody-drug conjugate comprising a CD19-targeting antibody and pyrrolobenzodiazepine dimers. A first-in-human study evaluated the safety and preliminary clinical activity of loncastuximab tesirine in patients with B-cell non-Hodgkin lymphoma (NHL).
Epratuzumab inhibits the production of the proinflammatory cytokines IL-6 and TNF-α, but not the regulatory cytokine IL-10, by B cells from healthy donors and SLE patients. [2018]Cytokines produced by B cells are believed to play important roles in autoimmune diseases. CD22 targeting by epratuzumab has been demonstrated to inhibit phosphorylation of B cell receptor (BCR) downstream signaling in B cells. It has been shown that other sialoadhesin molecules related to CD22 have immunoregulatory functions; therefore, in the present study, we addressed the role of epratuzumab on the production of key cytokines by B cells of patients with systemic lupus erythematosus (SLE) and of healthy donors (HD).