Chemotherapy + Targeted Therapy for Acute Lymphoblastic Leukemia

Recruiting in Seattle (>99 mi)

Overseen By Noah Pinke

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Must not be taking: Corticosteroids, Cytarabine

Disqualifiers: Burkitt lymphoma, CNS disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 24 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II clinical trial tests a chemotherapy regimen (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin with or without rituximab \[DA-EPOCH+/-R\]) with the addition of targeted therapy (tafasitamab) for the treatment of patients with newly diagnosed Philadelphia chromosome negative (Ph-) B acute lymphoblastic leukemia (B-ALL). Chemotherapy drugs, such as those in EPOCH+/-R, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Tafasitamab is in a class of medications called monoclonal antibodies. It works by helping the body to slow or stop the growth of cancer cells. Adding tafasitamab to the DA-EPOCH+/-R regimen may work better than DA-EPOCH+/-R alone in treating newly diagnosed Ph- B-ALL.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that no prior systemic therapy for ALL is allowed except to control acute symptoms, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drugs used in the Chemotherapy + Targeted Therapy for Acute Lymphoblastic Leukemia trial?

Research shows that a combination of drugs including prednisone, vincristine, and etoposide (VP-16) can lead to complete remission in some children with relapsed acute lymphoblastic leukemia (ALL). Additionally, a study found that a regimen including vincristine, doxorubicin, and prednisone achieved a high complete remission rate in adults with ALL. ^{1 2 3 4 5}

Is the combination of chemotherapy and targeted therapy for acute lymphoblastic leukemia generally safe in humans?

The research indicates that certain chemotherapy drugs like idarubicin and liposomal daunorubicin, when used in combination with other treatments, have shown low non-hematologic toxicity (side effects not related to blood) in patients with acute lymphoblastic leukemia. This suggests that these treatments can be generally safe for humans, although individual responses may vary. ^{6 7 8 9 10}

What makes the chemotherapy and targeted therapy treatment for acute lymphoblastic leukemia unique?

This treatment combines multiple drugs, including cyclophosphamide, doxorubicin, etoposide, prednisone, and vincristine, which are used together to target leukemia cells in different ways. The combination aims to improve outcomes by using drugs with different mechanisms of action, potentially overcoming resistance seen with other treatments. ^{1 2 3 11 12}

Research Team

Ryan D. Cassaday

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

This trial is for adults over 18 with newly-diagnosed Ph- B-ALL who can't use pediatric treatments, often due to age or other concerns. Participants need functioning kidneys and liver (with specific limits on enzyme levels), no severe blood count issues for subsequent treatment cycles, a performance status indicating they're not too sick to participate, and an expected survival beyond 3 months.

Inclusion Criteria

Marrow or blood involvement detectable by MFC

Total bilirubin =< 2.0 x upper limit of normal (ULN) (unless attributed to Gilbert's disease or other causes of inherited indirect hyperbilirubinemia, at which point total bilirubin must be =< 4.0 x ULN)

I am an adult with a new diagnosis of a specific type of leukemia.

Exclusion Criteria

May not be pregnant or nursing

I have only received emergency treatment for my acute lymphoblastic leukemia.

I have been diagnosed with Burkitt lymphoma/leukemia.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive DA-EPOCH+/-R chemotherapy and tafasitamab for up to 8 cycles, with each cycle lasting 21 days

24 weeks

Weekly visits for IV administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

5 years

Every 3 months for 2 years, then every 6 months for 3 years

Treatment Details

Interventions

• Cyclophosphamide
• Doxorubicin
• Etoposide
• Prednisone
• Tafasitamab
• Vincristine

Trial Overview The study tests DA-EPOCH+/-R chemotherapy combined with tafasitamab against the same chemo without tafasitamab in treating Ph- B-ALL. The goal is to see if adding the targeted therapy of tafasitamab improves outcomes by slowing cancer cell growth more effectively than chemotherapy alone.

Participant Groups

Group I: Treatment (DA-EPOCH+/-R, tafasitamab) Experimental Treatment 12 Interventions

Patients receive etoposide, doxorubicin, and vincristine IV continuously over 96 hours on days 1-4 of each cycle, cyclophosphamide IV over 1 hour on day 5 of each cycle, prednisone PO BID on days 1-5 of each cycle, and tafasitamab IV weekly on days 1, 8, and 15 of each cycle. CD20 positive patients also receive rituximab IV per guidelines on days 1 or 5 of each cycle. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration or biopsy, CT scan, lumbar puncture and undergo blood sample and cerebrospinal fluid collection throughout the trial.

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Findings from Research

In a study of 50 children with acute lymphoblastic leukemia (ALL) who were in their first to fifth relapse, a three-drug reinduction regimen including etoposide (VP-16) led to a complete remission in 34% of patients who received at least two courses of treatment.

The results suggest that prior resistance to teniposide (VM-26) does not prevent patients from responding to VP-16, indicating that higher doses and more frequent administration of VP-16 may effectively overcome resistance, although further research is needed for long-term treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etoposide (VP-16) with prednisone and vincristine for the treatment of refractory acute lymphoblastic leukemia. Abromowitch, M., Bowman, WP., Ochs, J., et al.[2017]

In a phase II study involving 20 heavily pretreated children with relapsed acute lymphoblastic leukemia (ALL), the combination of ifosfamide and etoposide (VP16) resulted in a 40% complete remission rate, demonstrating significant efficacy in this challenging patient population.

The treatment was generally well tolerated, with myelosuppression being the most common side effect, indicating that while the therapy is effective, careful monitoring for toxicity is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ifosfamide and etoposide in recurrent childhood acute lymphoblastic leukemia. Crooks, GM., Sato, JK.[2019]

In a study involving 105 children with late bone marrow relapses of acute lymphoblastic leukemia (ALL), 97% achieved a second complete remission, indicating that retreatment can be effective.

The trial did not conclusively determine a superior treatment regimen between doxorubicin/prednisone and cytarabine/teniposide, but identified key prognostic factors such as age under 10, lower white blood cell count at relapse, and longer initial remission duration that are associated with better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of late bone marrow relapse in children with acute lymphoblastic leukemia: a Pediatric Oncology Group study. Sadowitz, PD., Smith, SD., Shuster, J., et al.[2021]

In a study of 31 pediatric patients with relapsed acute lymphoblastic leukemia (ALL), topotecan administered before standard induction therapy resulted in an impressive 89.3% response rate, significantly reducing circulating blast cells.

The combination of topotecan with standard induction therapy led to a 74.2% complete response rate, indicating that this regimen is effective and well-tolerated, despite some hematologic and gastrointestinal toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of topotecan in combination with dexamethasone, asparaginase, and vincristine in pediatric patients with acute lymphoblastic leukemia in first relapse. Hijiya, N., Stewart, CF., Zhou, Y., et al.[2015]

In a study of 365 adults with acute lymphoblastic leukemia (ALL), those treated with the HCVAD chemotherapy regimen had a higher complete remission rate (91%) and better three-year event-free survival (40%) compared to those treated with the VAD regimen (73% and 23%, respectively).

The persistence of peripheral blood blasts on day 7 (D7PBb) and bone marrow blasts on day 14 (D14BMb) after starting chemotherapy had different prognostic implications depending on the treatment regimen, highlighting the importance of early clearance of leukemia cells for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Persistence of peripheral blood and bone marrow blasts during remission induction in adult acute lymphoblastic leukemia confers a poor prognosis depending on treatment intensity. Cortes, J., Fayad, L., O'Brien, S., et al.[2015]

In a clinical phase II study involving 70 patients with refractory or early relapse acute lymphoblastic leukemia (ALL) and T-cell non-Hodgkin's lymphoma (NHL), the combination of high-dose idarubicin and high-dose cytosine-arabinoside (ARA-C) resulted in a complete remission rate of 78%.

The treatment was well-tolerated, with limited non-hematologic side effects primarily related to infections, suggesting that this regimen could be a feasible option for patients with difficult-to-treat leukemia without compromising future bone marrow transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A single high dose of idarubicin combined with high-dose ARA-C (MSKCC ALL-3 protocol) in adult and pediatric patients with acute lymphoblastic leukemia. Experience at the University "La Sapienza" of Rome. Testi, AM., Moleti, ML., Giona, F., et al.[2013]

In a clinical phase II study involving 70 patients with refractory or early relapse acute lymphoblastic leukemia (ALL) and T-cell lymphoblastic non-Hodgkin's lymphoma (NHL), 78% achieved complete remission with the combination of high-dose idarubicin and high-dose cytosine-arabinoside, indicating strong antileukemic activity.

The treatment was well-tolerated, with limited non-hematologic side effects primarily related to infections, suggesting that this regimen could be a feasible option for patients while still allowing for potential bone marrow transplantation afterward.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A single high dose of idarubicin combined with high-dose ABA-C (MSKCC ALL-3 protocol) in adult and pediatric patients with acute lymphoblastic leukemia. Experience at the University La Sapienza of Rome. Testi, AM., Moleti, ML., Giona, F., et al.[2013]

In a study of 110 patients with metastatic Ewing sarcoma or primitive neuroectodermal tumor (PNET), the combination of topotecan and cyclophosphamide showed promising activity, with 21 out of 37 patients achieving partial responses.

Amifostine, intended as a cytoprotective agent, did not provide myeloprotection, and overall survival rates remained unchanged compared to previous studies, indicating that while some treatments showed activity, the prognosis for these patients remains poor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensive therapy with growth factor support for patients with Ewing tumor metastatic at diagnosis: Pediatric Oncology Group/Children's Cancer Group Phase II Study 9457--a report from the Children's Oncology Group. Bernstein, ML., Devidas, M., Lafreniere, D., et al.[2013]

In a study of 42 adult patients with poor-risk acute leukemia, the combination of liposomal daunorubicin (DNX) and high-dose arabinosyl cytosine (HDAC) resulted in a high complete remission rate of 51% in acute non-lymphocytic leukemia (ANLL) and 91% in acute lymphocytic leukemia (ALL).

The treatment was associated with low non-hematologic toxicity, making it a safer option for elderly and heavily pretreated patients, with negligible side effects such as no intestinal toxicity and only one case of bacteremia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal daunorubicin (DaunoXome) for treatment of poor-risk acute leukemia. Russo, D., Piccaluga, PP., Michieli, M., et al.[2013]

In a study testing 11 anti-cancer agents on 4 pediatric ALCL cell lines, vinblastine was found to be the most effective, significantly inhibiting cell growth in a time- and dose-dependent manner, with effective doses as low as 0.0002 microM/L after 24 hours.

Vinblastine treatment not only inhibited cell growth but also induced apoptosis and disrupted mitotic spindle formation, supporting its use as a first-line treatment in high-risk pediatric ALCL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antineoplastic agents for pediatric anaplastic large cell lymphoma: Vinblastine is the most effective in vitro. Muto, A., Nakagawa, A., Shimomura, Y., et al.[2019]

Leukemia cells from children with acute lymphoblast cell leukemia (ALL) showed significantly lower survival rates compared to those from acute myeloblast cell leukemia (AML), indicating that ALL cells may be more sensitive to treatment (p < 0.001).

Interferon-alpha 2b was found to enhance the cytotoxic effects of chemotherapy drugs like cytosar, vepeside, and doxorubicin on leukemia cells, particularly in ALL, suggesting it could be a valuable addition to treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Study of tumor cells sensitivity in patients with acute leukemia to cytokines and their combined use with drugs in vitro by MTT analysis]. Litvinova, EA., Mentkevich, GL., Chimishkian, KL.[2016]

In a study of 88 children with acute lymphoblastic leukemia, two treatment protocols showed high complete remission rates of 92-96%, with protocol 0276/A demonstrating a significantly lower relapse rate of 4% compared to 28% in protocol 0171.

The long-term outcomes were promising, with 60% of children from protocol 0171 remaining alive in complete remission for over 10 years, while protocol 0276/A showed even better results with over 70% of complete responders in continuous remission for up to 57 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of acute lymphoblastic leukemia in children. Long-term results of two trials. Cáp, J., Koza, I., Misíková, Z., et al.[2007]

References

1. United States pubmed.ncbi.nlm.nih.gov

Etoposide (VP-16) with prednisone and vincristine for the treatment of refractory acute lymphoblastic leukemia. [2017]

2. United States pubmed.ncbi.nlm.nih.gov

Ifosfamide and etoposide in recurrent childhood acute lymphoblastic leukemia. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Treatment of late bone marrow relapse in children with acute lymphoblastic leukemia: a Pediatric Oncology Group study. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Phase II study of topotecan in combination with dexamethasone, asparaginase, and vincristine in pediatric patients with acute lymphoblastic leukemia in first relapse. [2015]

5. United States pubmed.ncbi.nlm.nih.gov

Persistence of peripheral blood and bone marrow blasts during remission induction in adult acute lymphoblastic leukemia confers a poor prognosis depending on treatment intensity. [2015]

6. Italy pubmed.ncbi.nlm.nih.gov

A single high dose of idarubicin combined with high-dose ARA-C (MSKCC ALL-3 protocol) in adult and pediatric patients with acute lymphoblastic leukemia. Experience at the University "La Sapienza" of Rome. [2013]

7. Italy pubmed.ncbi.nlm.nih.gov

A single high dose of idarubicin combined with high-dose ABA-C (MSKCC ALL-3 protocol) in adult and pediatric patients with acute lymphoblastic leukemia. Experience at the University La Sapienza of Rome. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Intensive therapy with growth factor support for patients with Ewing tumor metastatic at diagnosis: Pediatric Oncology Group/Children's Cancer Group Phase II Study 9457--a report from the Children's Oncology Group. [2013]

9. Germany pubmed.ncbi.nlm.nih.gov

Liposomal daunorubicin (DaunoXome) for treatment of poor-risk acute leukemia. [2013]

10. United States pubmed.ncbi.nlm.nih.gov

Antineoplastic agents for pediatric anaplastic large cell lymphoma: Vinblastine is the most effective in vitro. [2019]

11. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Study of tumor cells sensitivity in patients with acute leukemia to cytokines and their combined use with drugs in vitro by MTT analysis]. [2016]

12. Slovakia pubmed.ncbi.nlm.nih.gov

Treatment of acute lymphoblastic leukemia in children. Long-term results of two trials. [2007]