ADCT-602 for B-Cell ALL

No longer recruiting at 1 trial location

Overseen By Nitin Jain, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Experimental medications

Disqualifiers: CNS leukemia, Burkitt's, GVHD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ADCT-602 for individuals with B-cell acute lymphoblastic leukemia (B-ALL) that has returned or isn't responding to standard treatments. Researchers aim to determine the optimal dose and understand the side effects of this treatment, which uses monoclonal antibodies—special proteins that bind to cancer cells—to inhibit cancer growth and spread. For those with B-ALL that recurs or resists therapy, and whose cancer cells show at least 20% CD22 protein, this trial may be suitable. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that ADCT-602 is likely to be safe for humans?

Research has shown that ADCT-602, a monoclonal antibody treatment, is being tested for safety in people. Monoclonal antibodies target specific cells, such as cancer cells, without harming healthy ones. ADCT-602 attaches to a protein called CD22 on some cancer cells and delivers a toxin to kill them.

In earlier studies, patients with B-cell lymphoblastic leukemia, a type of blood cancer, received ADCT-602. These studies aimed to find the right dose and monitor side effects. While the treatment appears promising, some patients experienced side effects, which is common in cancer treatments. These side effects can include tiredness, nausea, and low blood cell counts.

Since ADCT-602 is still in early testing stages, its safety is not fully known. These trials are crucial for understanding how well patients can tolerate the treatment and what side effects might occur. If ADCT-602 has been approved for another condition, it may suggest some level of safety, but this specific use is still under study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for B-cell acute lymphoblastic leukemia (B-Cell ALL), which often involve chemotherapy and targeted therapies like tyrosine kinase inhibitors, ADCT-602 offers a fresh approach by using an antibody-drug conjugate. This treatment specifically targets CD22, a protein commonly found on the surface of cancerous B-cells, delivering a potent drug directly to the cancer cells while sparing more healthy cells. Such targeted delivery can potentially reduce side effects and enhance effectiveness, making it an exciting prospect for patients with this type of leukemia.

What evidence suggests that ADCT-602 might be an effective treatment for B-cell ALL?

Research has shown that ADCT-602, the investigational treatment in this trial, may help treat B-cell acute lymphoblastic leukemia (B-ALL), particularly when the disease recurs or resists other treatments. ADCT-602 uses a special antibody to target a protein called CD22 on cancer cells, delivering a toxin directly to them. This method aims to halt the growth and spread of cancer cells. Early studies suggest this approach could be effective, but further research is needed to confirm these findings. Initial results indicate that this targeted method might improve outcomes for patients with relapsed or resistant B-ALL. ^{1 3 4 5 6}

Who Is on the Research Team?

Nitin Jain, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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

White blood cell (WBC) value of < 15,000 cells/uL prior to cycle 1 day 1

I am able to care for myself and perform daily activities.

Marrow blast count >= 5%

Exclusion Criteria

Known history of immunogenicity or hypersensitivity to a CD22 antibody

Known history of positive serum human adenosine deaminase (ADA)

Known seropositive for human immunodeficiency (HIV), hepatitis B, or hepatitis C virus with confirmatory testing

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation (Phase I)

Evaluate the safety and determine the maximum tolerated dose (MTD) of ADCT-602 in patients with relapsed or refractory B-cell acute lymphoblastic leukemia

21 days per cycle

1 visit (in-person) every 21 days

Treatment (Phase II)

Determine the recommended dose of ADCT-602 and evaluate efficacy in terms of complete response (CR) with incomplete marrow recovery (CR/CRi) rate

21-28 days per cycle

1 visit (in-person) every 21-28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

1 visit (in-person) at 30 days, then every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ADCT-602

Trial Overview 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.

How Is the Trial Designed?

Group I: ADCT-602 Experimental Treatment 1 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.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

ADC Therapeutics S.A.

Industry Sponsor

Trials

32

Recruited

2,700+

Published Research Related to This Trial

Epratuzumab effectively inhibits the production of proinflammatory cytokines IL-6 and TNF-α in B cells from patients with systemic lupus erythematosus (SLE) and healthy donors, suggesting its potential as a therapeutic intervention in autoimmune diseases.

The treatment does not affect the production of the regulatory cytokine IL-10, indicating that epratuzumab may help restore the balance between proinflammatory and regulatory cytokines in B cells, which is crucial for managing autoimmune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Fleischer, V., Sieber, J., Fleischer, SJ., et al.[2018]

A patient with Philadelphia chromosome-positive B-acute lymphoblastic leukemia (ALL) achieved a significant molecular remission after receiving radioimmunotherapy (RAIT) with (90) Y-labeled anti-CD22 epratuzumab tetraxetan, indicating its potential efficacy in treating this type of leukemia.

This case suggests that (90) Y-epratuzumab tetraxetan could be a promising therapeutic option for patients with CD22-positive B-ALL, especially for those in relapse, as the patient maintained remission for 6 months while awaiting a stem cell transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BCR-ABL1 molecular remission after 90Y-epratuzumab tetraxetan radioimmunotherapy in CD22+ Ph+ B-ALL: proof of principle. Chevallier, P., Bodet-Milin, C., Robillard, N., et al.[2017]

Epratuzumab, a monoclonal antibody targeting CD22, was found to be feasible and well-tolerated in a study involving 15 children with relapsed acute lymphoblastic leukemia (ALL), with only two dose-limiting toxicities reported.

The treatment led to effective targeting of leukemic cells, as indicated by the loss of CD22 expression in most patients, and resulted in complete remission for nine patients, with seven achieving minimal residual disease negativity after combined therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoimmunotherapy reinduction with epratuzumab in children with acute lymphoblastic leukemia in marrow relapse: a Children's Oncology Group Pilot Study. Raetz, EA., Cairo, MS., Borowitz, MJ., et al.[2021]

In a phase I study involving 88 patients with relapsed/refractory B-cell non-Hodgkin lymphoma, loncastuximab tesirine demonstrated a promising overall response rate of 59.4% at doses of 120 μg/kg or higher, with 40.6% achieving a complete response.

The treatment was associated with a high incidence of treatment-emergent adverse events (98.9%), primarily hematologic abnormalities and fatigue, but overall, it was considered to have acceptable safety, leading to the initiation of a phase II study at a starting dose of 150 μg/kg.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma. Kahl, BS., Hamadani, M., Radford, J., et al.[2020]

In a study involving adults with relapsed/refractory precursor B-acute lymphoblastic leukaemia (pre-B ALL), the addition of epratuzumab, a monoclonal antibody targeting CD22, to clofarabine and cytarabine resulted in a response rate of 52%, compared to only 17% with clofarabine and cytarabine alone.

This significant increase in response rate suggests that epratuzumab may enhance the effectiveness of chemotherapy for pre-B ALL, but further randomized trials are necessary to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SWOG S0910: a phase 2 trial of clofarabine/cytarabine/epratuzumab for relapsed/refractory acute lymphocytic leukaemia. Advani, AS., McDonough, S., Coutre, S., et al.[2021]

In a phase I/II study involving pediatric patients with B-lymphoblastic leukemia, the addition of epratuzumab to standard re-induction chemotherapy did not improve the rates of second remission (CR2), which remained at 65% and 66% for two different dosing schedules.

Epratuzumab was well tolerated, showing a similar safety profile to the chemotherapy alone, and there was a non-significant trend towards improved rates of minimal residual disease (MRD) negativity, suggesting potential benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Re-induction chemoimmunotherapy with epratuzumab in relapsed acute lymphoblastic leukemia (ALL): Phase II results from Children's Oncology Group (COG) study ADVL04P2. Raetz, EA., Cairo, MS., Borowitz, MJ., et al.[2018]

Epratuzumab is a monoclonal antibody targeting CD22, currently in phase 3 trials for systemic lupus erythematosus (SLE), which works by enhancing the inhibitory role of CD22 on B-cell receptor signaling, leading to reduced B-cell activation.

The treatment results in decreased B-cell proliferation, lower production of pro-inflammatory cytokines, and a modest reduction in peripheral B-cell numbers, indicating its potential to effectively modulate B-cell function in SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The mechanistic impact of CD22 engagement with epratuzumab on B cell function: Implications for the treatment of systemic lupus erythematosus. Dörner, T., Shock, A., Goldenberg, DM., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03698552

Study Details | NCT03698552 | ADCT-602 in Treating ... 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 ...

2. georgiacancerinfo.org georgiacancerinfo.org/clinical-trials/detail/5694

ADCT-602 in Treating Patients with Recurrent or Refractory ... This phase I/II trial studies the side effects and best dose of ADCT-602 in treating patients with B-cell acute lymphoblastic leukemia that has come back ( ...

3. adcreview.com adcreview.com/drugmap/adct-602-hll2-cys-pbd-epratuzumab-cys-tesirine/

Epratuzumab Tesirine | ADCT-602 | hLL2-cys-PBD Epratuzumab-cys tesirine or ADCT-602 is an ADC composed of a monoclonal antibody that binds to CD22 conjugated to a pyrrolobenzodiazepine (PBD) dimer toxin.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10985467/

ADCT-602, a Novel PBD Dimer–containing Antibody–Drug ... Relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) and lymphomas have poor patient outcomes; novel therapies are needed.

5. adctmedical.com adctmedical.com/wp-content/uploads/2021/12/A_Phase-1_Trial_of_ADCT_602_a_CD22_Targeting_ADC_Bound_to_PBD_Toxin_in_Adult_Patients_with_RR_CD22_B_Cell_ALL.pdf

A Phase 1 Trial of ADCT-602, a CD22 3+3 dose-escalation design was used. • ADCT-602 was initially given IV once every 3 weeks (starting dose 30 µg/kg). • Recently, based on the PK data, the ...

6. georgiacancerinfo.org georgiacancerinfo.org/trialDetailPrint.aspx?trialID=5694

Clinical Trial Details | GCI This phase I/II trial studies the side effects and best dose of ADCT-602 in treating patients with B-cell acute lymphoblastic leukemia that has come back ( ...