ADCT-602 for B-Cell ALL

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

57 Participants Needed

Trial Summary

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. ^{1 2 3 4 5}

What 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. ^{1 3 4 6 7}

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.

Research Team

Nitin Jain, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility 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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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, 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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

SWOG S0910: a phase 2 trial of clofarabine/cytarabine/epratuzumab for relapsed/refractory acute lymphocytic leukaemia. [2021]

2. United States 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. [2018]

3. United States 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. [2021]

4. Netherlands 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. [2018]

5. England pubmed.ncbi.nlm.nih.gov

BCR-ABL1 molecular remission after 90Y-epratuzumab tetraxetan radioimmunotherapy in CD22+ Ph+ B-ALL: proof of principle. [2017]

6. United States 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. [2020]

7. England 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. [2018]