Chemotherapy Regimen for Acute Lymphoblastic Leukemia

Not currently recruiting at 10 trial locations

Overseen By Lewis Silverman, MD

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Antineoplastics, Investigational agents

Disqualifiers: Mature B-cell ALL, HIV, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve treatment for acute lymphoblastic leukemia (ALL), a serious blood cancer that affects the body's ability to produce healthy blood cells. Researchers are testing a new method to tailor chemotherapy strength based on specific risk factors and to measure the dosing of a key drug, pegaspargase, a chemotherapy medication. Participants may qualify if they have been diagnosed with ALL and have not received previous cancer treatments, except for limited corticosteroids or emergency radiation. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does allow short courses of corticosteroids and a single dose of intrathecal cytarabine before registration. If you are on other medications, it's best to discuss with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that pegaspargase is safe and effective for treating acute lymphoblastic leukemia (ALL). Common side effects include low blood protein levels, changes in liver function, fever, and increased blood fat levels, mostly mild to moderate. The FDA has already approved pegaspargase for treating ALL.

Research has shown that dasatinib is generally safe for children with ALL, though it can cause serious side effects like bleeding, fluid buildup, and heart problems. It may also affect the liver, so past liver issues could increase the risk. Both drugs have known safety profiles, aiding doctors in managing any side effects during treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for acute lymphoblastic leukemia (ALL) because they offer a tailored approach based on the patient's risk level. Unlike the standard chemotherapy protocols, which may not be as precise, this trial includes personalized combinations and dosing of drugs like pegaspargase. For instance, the Reduced Dose Pegaspargase treatment adjusts doses based on individual patient needs, aiming to maintain optimal serum levels for effectiveness while potentially reducing side effects. Additionally, the use of dasatinib for patients with specific genetic markers (ABL1-class fusions) represents a targeted therapy approach, which can lead to more effective and less toxic treatment outcomes compared to conventional methods. This personalized strategy could revolutionize how ALL is treated by maximizing efficacy and minimizing unnecessary toxicity.

What evidence suggests that this trial's treatments could be effective for acute lymphoblastic leukemia?

Research has shown that pegaspargase, one of the treatments in this trial, greatly improves outcomes for patients with acute lymphoblastic leukemia (ALL). One study found that 84.9% of patients achieved a 5-year event-free survival (EFS), meaning they showed no signs of cancer returning or worsening during that period. This drug reduces asparagine, a nutrient cancer cells need to survive, which helps control the cancer. Pegaspargase has been part of treatment plans that have increased cure rates, with over 90% of children now surviving ALL, making it an essential component of chemotherapy for this type of leukemia. ^{6 7 8 9 10}

Who Is on the Research Team?

Melissa A. Burns

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for children and adolescents aged 1 to less than 22 years with a confirmed diagnosis of acute lymphoblastic leukemia (ALL). They must not have had previous cancer treatments, except for short-term corticosteroids or emergent radiation. Participants need parental consent and cannot have chronic steroid use, HIV, uncontrolled illnesses, or be pregnant.

Inclusion Criteria

I have received a dose of cytarabine in my spine before joining this study.

I am between 1 and 21 years old.

Direct bilirubin < 1.4 mg/dL (23.9 micromoles/L).

Exclusion Criteria

Currently receiving any investigational agents.

My leukemia is classified as mixed phenotype or ambiguous lineage.

I do not have any severe illnesses or conditions that could interfere with the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive initial treatment to induce remission, including vincristine, dexamethasone, pegaspargase, and other drugs based on risk group

4-6 weeks

Consolidation

Participants receive further treatment to eliminate remaining leukemia cells, including high-dose methotrexate, mercaptopurine, and other drugs based on risk group

8-12 weeks

CNS Phase

Participants receive treatment targeting the central nervous system, including vincristine, dexamethasone, mercaptopurine, and IT chemotherapy

4 weeks

Continuation

Participants receive ongoing treatment to maintain remission, including vincristine, dexamethasone, mercaptopurine, and methotrexate

18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-5 years

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Cytarabine
• Dasatinib
• Dexamethasone
• Dexrazoxane
• Doxorubicin
• Erwinia Asparaginase
• Etoposide
• Hydrocortisone
• Leucovorin Calcium
• Mercaptopurine
• Methotrexate
• Pegaspargase
• Vincristine

Trial Overview The study tests an updated set of risk factors to determine the intensity of ALL treatment in young patients. It also explores a new dosing method for pegaspargase based on drug levels in the blood. The trial includes various chemotherapy drugs like Doxorubicin and Vincristine over about two years.

How Is the Trial Designed?

Group I: Reduced Dose (PK-Adjusted) Pegaspargase Experimental Treatment 2 Interventions

Final LR, IR, HR patients who consent to randomization and are assigned to receive 15 doses of pegaspargase every 2-weeks beginning at a reduced dose (2000 IU/m2/dose); subsequent doses adjusted based on nadir serum asparaginase activity (NSAA) levels, with goal of maintaining NSAA between 0.4 and 1.0 IU/mL. Closed to Enrollment.

Group II: Initial Very High Risk (Initial VHR) Experimental Treatment 15 Interventions

Any of the following are present: IKZF1 deletion, MLL (KMT2A) rearrangement, low hypodiploidy, t(17;19) Treated with Induction IA (vincristine, dexamethasone, pegaspargase, doxorubicin + dexrazoxane), Induction IB (cyclophosphamide, cytarabine, mercaptopurine), Consolidation IA (vincristine, high-dose methotrexate + leucovorin, mercaptopurine). IT chemotherapy in all phases. Final risk group assigned by end of Consolidation IA.

Group III: Initial Low Risk (Initial LR) Experimental Treatment 10 Interventions

Meets all the following criteria: B-ALL, Age 1-\<15 years, WBC \< 50,000/microliter, CNS-1 or CNS-2, no BCR-ABL1, no iAMP21, and no VHR characteristics. Treated with Induction IA (vincristine, dexamethasone, pegaspargase), Induction IB (cyclophosphamide, cytarabine, mercaptopurine), Consolidation IA (vincristine, high-dose methotrexate + leucovorin, mercaptopurine). IT chemotherapy in all phases. Final risk group assigned by end of Consolidation IA.

Group IV: Initial High Risk (Initial HR) Experimental Treatment 12 Interventions

Meets at least one of the following criteria: Age \>=15 years, WBC \>=50,000/microliter, CNS-3, T-ALL, iAMP21, BCR-ABL1 And: No VHR characteristics Treated with Induction IA (vincristine, dexamethasone, pegaspargase, doxorubicin + dexrazoxane), Induction IB (cyclophosphamide, cytarabine, mercaptopurine), Consolidation IA (vincristine, high-dose methotrexate + leucovorin, mercaptopurine). IT chemotherapy in all phases. Final risk group assigned by end of Consolidation IA.

Group V: Final Very High Risk (Final VHR) Experimental Treatment 15 Interventions

Initial VHR or any patient with high MRD (\>=0.001) at second time point (week 10-12) Final Risk Group assigned at end of Consolidation IA. Subsequent therapy as follows: Consolidation IB/B-ALL (High-dose methotrexate + leucovorin, cyclophosphamide, etoposide, IT chemotherapy); Consolidation IB/T-ALL (nelararbine, cyclophosphamide, etoposide); Consolidation IC (High-dose cytarabine, etoposide, dexamethasone, pegaspargase \[by direct assignment\], IT chemotherapy); CNS phase (vincristine, dexamethasone, mercaptopurine, pegaspargase \[by direct assignment\], IT chemotherapy); Consolidation II (vincristine, dexamethasone, mercaptopurine, doxorubicin + dexrazoxane, pegaspargase \[by direct assignment\], IT chemotherapy); Continuation (vincristine, dexamethasone, mercaptopurine, methotrexate, IT chemotherapy). Dasatinib administered daily during all phases to pts with ABL1-class fusions. All treatment completed 24 months from date of complete remission.

Group VI: Final Low Risk (Final LR) Experimental Treatment 8 Interventions

Initial Low Risk and Low MRD (\<0.0001) at first time point (Day 32) Final Risk Group assigned at end of Consolidation IA. Subsequent therapy as follows: CNS phase (vincristine, dexamethasone, mercaptopurine, pegaspargase \[by randomization or direct assignment\], IT chemotherapy); Consolidation II (vincristine, dexamethasone, mercaptopurine, methotrexate, pegaspargase \[by randomization or direct assignment\], IT chemotherapy); Continuation (vincristine, dexamethasone, mercaptopurine, methotrexate, IT chemotherapy). All treatment completed 24 months from date of complete remission.

Group VII: Final Intermediate Risk (Final IR) Experimental Treatment 10 Interventions

Initial High Risk and Low MRD (\<0.0001) at first time point (Day 32) Final Risk Group assigned at end of Consolidation IA. Subsequent therapy as follows: CNS phase (vincristine, dexamethasone, mercaptopurine, pegaspargase \[by randomization or direct assignment\], IT chemotherapy); Consolidation II (vincristine, dexamethasone, mercaptopurine, doxorubicin + dexrazoxane, pegaspargase \[by randomization or direct assignment\], IT chemotherapy); Continuation (vincristine, dexamethasone, mercaptopurine, methotrexate, IT chemotherapy). All treatment completed 24 months from date of complete remission.

Group VIII: Final High Risk (Final HR) Experimental Treatment 10 Interventions

Initial Low Risk or Initial High Risk with High MRD (\>=0.0001) at first time point (Day 32) but low MRD (\<0.001) at second time point (week 10-12) Final Risk Group assigned at end of Consolidation IA. Subsequent therapy as follows: CNS phase (vincristine, dexamethasone, mercaptopurine, pegaspargase \[by randomization or direct assignment\], IT chemotherapy); Consolidation II (vincristine, dexamethasone, mercaptopurine, doxorubicin + dexrazoxane, pegaspargase \[by randomization or direct assignment\], IT chemotherapy); Continuation (vincristine, dexamethasone, mercaptopurine, methotrexate, IT chemotherapy). All treatment completed 24 months from date of complete remission.

Group IX: Direct Assignment Experimental Treatment 2 Interventions

All VHR patients, and any Final LR, IR, HR patients who decline randomization: Assigned to receive standard dosing of pegaspargase (15 doses of pegaspargase every 2-weeks at standard fixed-dose; 2500 IU/m2/dose).

Group X: Fixed Dose Pegaspargase Active Control 2 Interventions

Final LR, IR, HR patients who consent to randomization and are assigned to receive 15 doses of pegaspargase every 2-weeks at standard fixed-dose (2500 IU/m2/dose).

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?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Servier

Industry Sponsor

Trials

55

Recruited

45,600+

Citations

1. oncaspar.com oncaspar.com/hcp/safety-efficacy

Proven Efficacy and Safety 84.9% of patients achieved 5-year EFS with ONCASPAR when administered for the full duration as part of a treatment regimen for ALL.1. DFCI 11-001 Study Design.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6531401/

Pegaspargase: A Review in Acute Lymphoblastic Leukaemia Pegaspargase had a manageable tolerability profile in paediatric and adult patients with newly diagnosed ALL, with the most commonly occurring ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9279693/

Current Use of Asparaginase in Acute Lymphoblastic ... Pediatric Acute Lymphoblastic Leukemia (ALL) cure rates have improved exponentially over the past five decades with now over 90% of children ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01574274?term=CALASPARGASE%20PEGOL&rank=8

Study Details | SC-PEG Asparaginase vs. Oncaspar in ... Asparaginase is used to treat ALL and lymphoblastic lymphoma. The standard form of asparaginase, called Elspar, is given in the muscle once a week for 30 weeks.

5. ashpublications.org ashpublications.org/blood/article/109/10/4164/22891/Effective-asparagine-depletion-with-pegylated

Effective asparagine depletion with pegylated asparaginase ... Effective asparagine depletion with pegylated asparaginase results in improved outcomes in adult acute lymphoblastic leukemia: Cancer and Leukemia Group B Study ...

6. sprycel-hcp.com sprycel-hcp.com/safety-newly-diagnosed

SPRYCEL® (dasatinib) Safety Profile - Newly Diagnosed ... SPRYCEL is associated with the following warnings and precautions: myelosuppression, bleeding-related events, fluid retention, cardiovascular toxicity, ...

7. lymphoblastic-hub.com lymphoblastic-hub.com/medical-information/dasatinib-real-world-safety-profiles-in-pediatric-patients

Dasatinib real-world safety profiles in pediatric patients A real-world study analyzing the safety data of dasatinib in pediatric patients with malignancies, including Philadelphia ...

8. fda.gov fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-sprycel-dasatinib-and-risk-pulmonary-arterial-hypertension

Sprycel (dasatinib) and risk of pulmonary arterial ... (10/11/2011) FDA is warning the public that the leukemia drug Sprycel (dasatinib) may increase the risk of a rare, but serious condition in ...

9. mayoclinic.org mayoclinic.org/drugs-supplements/dasatinib-oral-route/description/drg-20070797

Dasatinib (oral route) - Side effects & dosage It is also used to treat Ph+ CML and Philadelphia chromosome positive acute lymphoblastic leukemia ... Safety and efficacy have been established.

10. sprycel.com sprycel.com/

SPRYCEL® (dasatinib) - Official Patient Website Liver problems: SPRYCEL can cause liver problems. People who have had liver problems in the past may be at risk for getting liver problems with SPRYCEL. Your ...