Pegaspargase and Combination Chemotherapy in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

NCT01005914 | Terminated Phase 2 Results DMC

• 4 other identifiers: IRB00004913OHSU-4913ENZON-OHSU-4913CDR0000642363
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. PURPOSE: This phase II trial is studying the side effects of giving pegaspargase together with combination chemotherapy and to see how well it works in treating patients with newly diagnosed acute lymphoblastic leukemia.

Conditions

Leukemia

Keywords

adults; Philadelphia chromosome precursor ALL,; T-cell ALL; untreated ALL

Outcome Measures

Primary Outcomes (2)

• Complete Response Rate After Course 1 of Pegaspargase When Administered in Combination With Hyper-CVAD Regimen

  The complete response rate after 1A cycle of a PEG-Asparaginase and hyper-CVAD combination regimen will be estimated, and an exact 95% confidence interval will be computed using a binomial distribution.

  After day 4 of treatment

• Grade 3 and 4 Toxicity Associated With the Combination of Peg-Asparaginase and Hyper-CVAD Which Include: Allergic Reactions, Elevated Liver Enzymes, Hyperbilirubinemia, Hyperglycemia, Central Nervous System (CNS) Thrombosis, and Pancreatitis.

  The assessment of safety will be based mainly on the frequency of adverse events

Secondary Outcomes (5)

• 2-year Progression-free Survival

  After completion of 8 cycles

• Proportion of Patients Who Achieve Complete Response or Partial Response After Courses 1 and 2

  An interim analysis of safety is planned after the enrollment of 15 evaluable patients.

• Overall Survival

  At least every 6 months until death.

• Rate of Minimal Residual Disease

  End of cycles 1A and 1B

• Half-life of Pegaspargase

  The approximate t½ in adult patients is 5.73 days. The half-life is independent of the dose administered, disease status, renal or hepatic function, age, or gender.

Study Arms (1)

Group 1

EXPERIMENTAL

Drug:cyclophosphamide Day 1- 3: 300 m g/m2 IV over 2-3 hours every 12 hours for 6 doses plus mesna 600 mg/ m2 /day continuous infusion Days 1-3 Drug:cytarabine Day 2 \& 3: 3g/m2 IV over 2 hours q12 X 4 Drug:dexamethasone Day 1-4; 11-14: 40 mg daily Drug:doxorubicin hydrochloride Day 4: 50 mg/m2 IV over 2 hours Drug:imatinib mesylate 600 mg/day Drug:methotrexate Day 1: 1g/ m2 (200 mg/ m2load IV over 2 hours plus 800 mg/ m2 over 22 hours as an infusion Drug: methylprednisolone Day 1-3: 50mg IV BID Drug: pegaspargase Day 3/Day4: 2,500 IU/ m2 IV Drug: vincristine sulfate Day 4 \& 11: 2 mg IV

Drug: cyclophosphamide; Drug: cytarabine; Drug: dexamethasone; Drug: doxorubicin hydrochloride; Drug: imatinib mesylate; Drug: methotrexate; Drug: methylprednisolone; Drug: pegaspargase; Drug: vincristine sulfate

Interventions

cyclophosphamide DRUG

Day 1- 3: 300 m g/m2 IV over 2-3 hours every 12 hours for 6 doses plus mesna 600 mg/ m2 /day continuous infusion Days 1-3

Also known as: Cytoxan, Neosar, CTX

Group 1

cytarabine DRUG

Day 2 \& 3: 3g/m2 IV over 2 hours q12 X 4

Also known as: Cytosar-U, Ara-C, Arabinosylcytosine

Group 1

dexamethasone DRUG

Day 1-4; 11-14: 40 mg daily

Also known as: Decadron, DexPak, dex

Group 1

doxorubicin hydrochloride DRUG

Day 4: 50 mg/m2 IV over 2 hours

Also known as: Adriamycin RDF, Adriamycin PFS

Group 1

imatinib mesylate DRUG

600 mg/day

Also known as: Gleevec, Glivec

Group 1

methotrexate DRUG

Day 1: 1g/ m2 (200 mg/ m2load IV over 2 hours plus 800 mg/ m2 over 22 hours as an infusion

Also known as: Trexall, Rheumatrex, MTX

Group 1

methylprednisolone DRUG

Day 1-3: 50mg IV BID

Also known as: Medrol, Depo-Medrol, Solu-Medrol

Group 1

pegaspargase DRUG

Day 3/Day4: 2,500 IU/ m2 IV

Also known as: Onscapar, PEG-L-asparaginase

Group 1

vincristine sulfate DRUG

Day 4 \& 11: 2 mg IV

Also known as: Marqibo

Group 1

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients must be newly diagnosed (untreated) with Acute Lymphoblastic Leukemia based on a bone marrow examination unless there is a contraindication to having the test performed. This includes precursor-B ALL, precursor-T ALL, and Philadelphia chromosome positive ALL. For reference, see criteria by Center for International Blood and Marrow Transplant Research (CIBMTR).\> 20% blasts on a bone marrow aspirate OR If a bone marrow aspirate is not obtained, the diagnosis of acute leukemia can be established by a pathologic diagnosis of acute leukemia on a bone marrow biopsy OR A complete blood count documenting the presence of at least 10,000 white blood cells (WBC)/μl and at least 20% circulating blasts
• Adults, 18 to 60 years of age.
• Women of child bearing potential (WOCBP) must be willing to use adequate contraception to avoid pregnancy for the duration of study participation.
• Eastern Cooperative Oncology Group (ECOG) performance status \< 2
• Adequate renal function defined as: Serum creatinine ≤ 2.0 x upper limit normal (ULN) for institution
• Adequate hepatic function defined as:Total bilirubin ≤ 2.0 x ULN for institution Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.0 x ULN for institution
• Patient must have the ability to understand and the willingness to sign a written informed consent document. The patient and/or the patient's legally authorized guardian must acknowledge consent for treatment as a human subject on this study.

You may not qualify if:

• Mature B (Burkitt's) ALL will be excluded.
• An active malignancy other than ALL (with the exception of basal and/or squamous cell skin cancers and curatively treated carcinoma of the cervix) within 5 past years of study entry.
• Documented central nervous system (CNS) involvement with leukemia will be excluded. A diagnostic lumbar puncture will not be part of screening procedures.
• Severe pulmonary, renal, or hepatic disease not related to the patient's ALL will be excluded.
• Cardiac dysfunction as defined by:Myocardial infarction within the last 6 months of study entry, or Reduced left ventricular function with an ejection fraction ≤50% as measured by Multigated Acquisition (MUGA) scan or echocardiogram at study entry, Unstable angina, Unstable cardiac arrhythmias, New York Heart Association (NYHA) Class III or IV heart failure, Electrocardiographic evidence of acute ischemia or active conduction system abnormalities
• Known or suspected human immunodeficiency virus (HIV)-positive patients are excluded from the study because of possible risk of lethal infection when treated with marrow suppressive therapy.
• Any concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, etc.) or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• Patients who have had chemotherapy or radiotherapy for ALL prior to entering the study will be excluded. Hydroxyurea and one dose of intravenous vincristine are allowed prior to registration for patient convenience. Prior steroid therapy is allowable, ≤5 days prior to the start of the regimen.
• Patients may not have received any other investigational agents within the last 30 days.
• WOCBP who are unwilling or unable to use an acceptable method of contraception for the entire study period. Pregnant or lactating women are excluded from this study because of possible risk to the fetus or infant. Women with a positive serum pregnancy test on enrollment or prior to study drug administration will be excluded.
• Men whose sexual partners are WOCBP, who are unwilling or unable to use an acceptable contraceptive method to avoid pregnancy of his partner for the entire study period.

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Leukemia; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Cyclophosphamide; Cytarabine; Dexamethasone; Calcium Dobesilate; Doxorubicin; Imatinib Mesylate; Methotrexate; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; pegaspargase; Vincristine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Aminoglycosides; Glycosides; Carbohydrates; Benzamides; Amides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Piperazines; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Prednisolone; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Limitations and Caveats

Study terminated early due to safety concerns. Only one subject completed the study.

Results Point of Contact

• Title: Dr. Brandon Hayes-Lattin
• Organization: Oregon Health & Science University

hayeslat@ohsu.edu

503-494-1551

Study Officials

• Brandon Hayes-Lattin

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Brandon M. Hayes-Lattin, M.D.

Study Record Dates

• First Submitted: October 30, 2009
• First Posted: November 2, 2009
• Study Start: June 1, 2009
• Primary Completion: March 1, 2013
• Study Completion: May 1, 2014
• Last Updated: January 6, 2023
• Results First Posted: February 11, 2015

Record last verified: 2022-12

Locations

US (1)