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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

72%

Neutrophil count decreased

57%

Infections and infestations - Other, specify

54%

Febrile neutropenia

47%

Alanine aminotransferase increased

39%

White blood cell decreased

39%

Platelet count decreased

32%

Hyperglycemia

27%

Anemia

24%

Aspartate aminotransferase increased

22%

Mucositis oral

19%

Hypokalemia

18%

Blood bilirubin increased

18%

Hyponatremia

16%

Anorexia

15%

Abdominal pain

15%

Vomiting

15%

Lipase increased

14%

Anaphylaxis

13%

Dehydration

13%

Headache

13%

Peripheral motor neuropathy

10%

Nausea

10%

Hypocalcemia

Hypoalbuminemia

Diarrhea

Hypoxia

Lung infection

Peripheral sensory neuropathy

Fibrinogen decreased

Avascular necrosis

Back pain

Serum amylase increased

Weight loss

Enterocolitis infectious

Depression

Fever

Hypotension

Pancreatitis

Hypophosphatemia

Pain in extremity

Arthralgia

Epistaxis

Lymphocyte count decreased

Upper respiratory infection

Hyperkalemia

Skin infection

Acute kidney injury

GGT increased

Pain

Dyspnea

Hypertension

Oral pain

Activated partial thromboplastin time prolonged

Bone pain

Typhlitis

Hypertriglyceridemia

Seizure

Urinary tract infection

Sinusitis

Glucose intolerance

Creatinine increased

Encephalopathy

Ileus

Pneumonitis

Syncope

Anxiety

Colitis

Fatigue

Rash maculo-papular

Thromboembolic event

Tumor lysis syndrome

Nervous system disorders - Other, specify

Esophagitis

Catheter related infection

Hypermagnesemia

Disseminated intravascular coagulation

Cough

Urticaria

Hemolysis

Dysphagia

Hypercalcemia

Hepatic failure

Acidosis

Confusion

Hypernatremia

Non-cardiac chest pain

Personality change

Vascular disorders - Other, specify

Anal mucositis

Dysphasia

Hypoglycemia

INR increased

Vascular access complication

Pleural effusion

Abdominal infection

Hematoma

Capillary leak syndrome

Intracranial hemorrhage

Hepatobiliary disorders - Other, specify

Gastrointestinal disorders - Other, specify

Dizziness

Allergic reaction

Hepatic infection

Psychosis

Skin ulceration

Pharyngitis

Ascites

Bone marrow hypocellular

Facial nerve disorder

Rectal pain

Hyperuricemia

Insomnia

Pancreas infection

Pharyngeal mucositis

Pneumothorax

Proteinuria

Muscle weakness lower limb

Anal pain

Cholecystitis

Enterocolitis

Hypomagnesemia

Immune system disorders - Other, specify

Investigations - Other, specify

Iron overload

Proctitis

Respiratory, thoracic and mediastinal disorders - Other, specify

Stomach pain

Musculoskeletal and connective tissue disorder - Other, specify

Weight gain

Blood and lymphatic system disorders - Other, specify

Adult respiratory distress syndrome

Myositis

Pharyngolaryngeal pain

Gastritis

100%

80%

60%

40%

20%

Study treatment Arm

Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old

Prednisone and High Dose Methotrexate < 10 Yrs Old

Prednisone and High Dose Methotrexate (Non Randomly Assigned)

Dexamethasone, High Dose Methotrexate (IM) < 10 Years

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

Erwinia asparaginase

2012

Completed Phase 2

~30