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Alkylating agents

Chemotherapy Regimen for Acute Lymphoblastic Leukemia

Phase 3

Waitlist Available

Led By Lewis Silveman, MD

Research Sponsored by Dana-Farber Cancer Institute

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age: 365 days to < 22 years

Prior Therapy: No prior therapy is allowed except for the following:

Must not have

World Health Organization diagnostic criteria of mixed phenotype acute leukemia (MPAL) or leukemia of ambiguous lineage

Uncontrolled intercurrent illness including, but not limited to ongoing infection with vital sign instability (hypotension, respiratory insufficiency), life-threatening acute tumor lysis syndrome (eg, with renal failure), symptomatic congestive heart failure, cardiac arrhythmia, intracranial or other uncontrolled bleeding, or psychiatric illness/social situations that would limit compliance with study requirements.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up during post-induction therapy with 30-weeks of pegaspargase (15 doses), collected during the first 6 months of therapy for all participants through study completion (expected to take 4-5 years to accrue)

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is studying a new way to treat acute lymphoblastic leukemia (ALL). The new way involves using a new, updated set of risk factors to decide how strong the treatment will be and testing a new way of dosing a chemotherapy drug.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Chemotherapy drugs used may cause side effects such as nausea, vomiting, hair loss, fatigue, increased infection risk due to low blood cell counts, mouth sores, and potential damage to organs like the heart and liver.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 1 and 21 years old.

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I have not received any treatments except for allowed ones.

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I have not been on corticosteroids for more than 7 days in the last month or more than 28 days in the last 6 months.

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I have been diagnosed with acute lymphoblastic leukemia.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My leukemia is classified as mixed phenotype or ambiguous lineage.

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

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I am not pregnant or breastfeeding.

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I am HIV-positive.

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I have not had chemotherapy or radiotherapy for another cancer.

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My leukemia is a type called Burkitt's with specific genetic features.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ during post-induction therapy with 30-weeks of pegaspargase (15 doses). collected during the first 6 months of therapy for all participants through study completion (expected to take 4-5 years to accrue)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~during post-induction therapy with 30-weeks of pegaspargase (15 doses). collected during the first 6 months of therapy for all participants through study completion (expected to take 4-5 years to accrue)

This trial's timeline: 3 weeks for screening, Varies for treatment, and during post-induction therapy with 30-weeks of pegaspargase (15 doses). collected during the first 6 months of therapy for all participants through study completion (expected to take 4-5 years to accrue) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Nadir Serum Asparaginase Activity (NSAA)

Non-allergic Asparaginase Toxicity

Side effects data

From 2021 Phase 3 trial • 3154 Patients • NCT00075725

82%

Neutrophil count decreased

68%

Infections and infestations - Other, specify

65%

Febrile neutropenia

46%

Alanine aminotransferase increased

45%

White blood cell decreased

38%

Platelet count decreased

33%

Anemia

26%

Aspartate aminotransferase increased

20%

Hypokalemia

14%

Anaphylaxis

13%

Mucositis oral

13%

Hyponatremia

12%

Hyperglycemia

12%

Diarrhea

10%

Dehydration

10%

Lymphocyte count decreased

10%

Anorexia

Upper respiratory infection

Abdominal pain

Vomiting

Lung infection

Blood bilirubin increased

Fever

Hypocalcemia

Enterocolitis infectious

Catheter related infection

Hypoxia

Lipase increased

Peripheral motor neuropathy

Serum amylase increased

Hypoalbuminemia

Peripheral sensory neuropathy

Urinary tract infection

Otitis media

Fibrinogen decreased

Colitis

Sinusitis

Pancreatitis

Skin infection

Pneumonitis

Rash maculo-papular

Activated partial thromboplastin time prolonged

Typhlitis

Hypoglycemia

Hypophosphatemia

Hypotension

Nausea

Constipation

Respiratory, thoracic and mediastinal disorders - Other, specify

Ileus

Seizure

GGT increased

Hypertension

Pain

Tumor lysis syndrome

Weight loss

Hyperkalemia

Pleural effusion

Portal hypertension

Pain in extremity

Disseminated intravascular coagulation

Depressed level of consciousness

Agitation

Buttock pain

Conjunctivitis infective

Nervous system disorders - Other, specify

Upper gastrointestinal hemorrhage

Gastrointestinal disorders - Other, specify

Gait disturbance

Epistaxis

Ascites

Anxiety

Bronchial infection

Arthralgia

Blood and lymphatic system disorders - Other, specify

Depression

Fatigue

Flu like symptoms

Rectal pain

Headache

Insomnia

Oral pain

Sepsis

Vascular disorders - Other, specify

Hyperuricemia

Cough

Device related infection

Enterocolitis

Esophagitis

Hypercalcemia

Middle ear inflammation

Immune system disorders - Other, specify

Investigations - Other, specify

Neuralgia

Stomach pain

Thromboembolic event

Weight gain

Wound infection

Cardiac disorders - Other, specify

Creatinine increased

100%

80%

60%

40%

20%

Study treatment Arm

Dexamethasone, High Dose Methotrexate (IM) < 10 Years

Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old

Prednisone and High Dose Methotrexate < 10 Yrs Old

Prednisone and High Dose Methotrexate (Non Randomly Assigned)

Prednisone, Capezzi Methotrexate >= 10 Years

Prednisone, Capizzi Methotrexate <10 Years

Dexamethasone and Capizzi Methotrexate Patients < 10 Years

Dexamethasone, High Dose Methotrexate (Non Randomly Assigned)

Prednisone and High Dose Methotrexate >=10 Years

Dexamethasone, High Dose Methotrexate (IM) >= 10 Years

Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random)

Prednisone, Capezzi Methotrexate (Down's Syndrome)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

10Treatment groups

Experimental Treatment

Active Control

Group I: Reduced Dose (PK-Adjusted) PegaspargaseExperimental Treatment2 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 Treatment15 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 Treatment10 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 Treatment12 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 Treatment15 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 Treatment8 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 Treatment10 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 Treatment10 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 AssignmentExperimental Treatment2 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 PegaspargaseActive Control2 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).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

METHOTREXATE

2015

Completed Phase 4

~30

MERCAPTOPURINE

2015

Completed Phase 4

~220