Chemotherapy With Liposomal Cytarabine CNS Prophylaxis for Adult Acute Lymphoblastic Leukemia & Lymphoblastic Lymphoma

NCT02043587 | Terminated Phase 2 DMC

• 1 other identifier: 130934
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 4

Brief Summary

The objective of this protocol is to improve survival for adults with acute lymphoblastic leukemia or acute lymphoblastic lymphoma by reducing systemic and central nervous system (CNS) relapse with acceptable toxicity using intensive chemotherapy with liposomal cytarabine (Depocyt®) CNS prophylaxis.

Conditions

Acute Lymphocytic Leukemia; Adult Lymphoblastic Lymphoma

Keywords

Acute lymphoblastic leukemia; Lymphoblastic leukemia; Lymphoblastic lymphoma

Outcome Measures

Primary Outcomes (1)

• Event-free survival

  3-year

Secondary Outcomes (8)

• Liposomal cytarabine toxicity

  3 years

• CNS relapse rate

  3-year

• Overall survival

  3-year

• Leukemia-free survival

  3-year

• Efficacy of hydrocortisone premedication for reduced PEG-asparaginase allergic reactions

  3 years

Other Outcomes (2)

• Minimal residual disease and outcomes

  3 years

• Asparaginase antibodies and asparaginase activity

  3 years

Study Arms (1)

Chemotherapy for ALL

EXPERIMENTAL

Course 1A: DNR 60 mg/m2 IV d1,2,3; VCR 1.4 mg/m2 d1,8,15,22 (cap 2 mg age \>50); PEG-asp 2000 IU/m2 IV d16, age \>50 1000 IU/m2, cap 3750 IU/m2; CTX 750 mg/m2 d1,15 age \< 40; Prednisone 60 mg/m2 PO d1-28; Liposomal AraC 25 mg IT d1, 15 1B: MTX 220 mg/m2 IV then 60 mg/m2/h for 36h d2-3,d16-17; LCV 50 mg/m2 IV q6h x3 then 10 mg/m2 PO/IV q6h til MTX \<0.1 uM; 6-MP 60 mg/m2 PO d2-8, d16-22; PEG-asp 2000 IU/m2 IV d18, age \>50 1000 IU/m2, cap 3750 IU/m2 1C: AraC 2 g/m2 IV d1-4; Etoposide 500 mg/m2 IV d1-4 1A-C repeat x1(2A-C) then 3rd Course B (3B) Maintenance (monthly, 24 mo): Prednisone 60 mg/m2 PO d1-5; VCR 1.4 mg/m2 IV d1 (cap 2 mg age \>50); MTX 20 mg/m2 PO wkly; 6-MP 60 mg/m2 PO qd PEG-asp 2000 IU/m2 IV d16, age \>50 1000 IU/m2, cap 3,750 IU/m2 (Mo. 1) Maintenance mo. 1-4: Liposomal AraC 50 mg IT d1 Dasatinib 140 mg PO qd if Ph/BCR-ABL+; Rituximab 375 mg/m2 IV d1,15 of 1A-C, 2A (Pre-B) 1:1 randomization: hydrocortisone v. placebo before PEG-asp 1B, 2B, \& Maint.

Drug: DNR; Drug: VCR; Drug: PEG-asp; Drug: CTX; Drug: Prednisone; Drug: Liposomal AraC; Drug: MTX; Drug: LCV; Drug: AraC; Drug: Etoposide; Drug: Dasatinib; Drug: Rituximab; Drug: Hydrocortisone

Interventions

DNR DRUG

Daunorubicin 60 mg/m2 IV (in the vein) daily 1,2,3 Courses 1A, 2A

Also known as: Daunorubicin, Daunorubicin Hydrochloride, Cerubidine, Daunomycin, Rubidomycin

Chemotherapy for ALL

VCR DRUG

1.4 mg/m2 IV, days 1, 8, 15, 22 (cap at 2mg for ages \>50) during Courses 1A, 2A; Maintenance: Day 1 during months 2-12

Also known as: Vincristine, Oncovin, Vincasar, PFS, Vincrex, Leurocritine, LCR

Chemotherapy for ALL

PEG-asp DRUG

2,000 IU/m2 IV for ages \</= 50, age \> 50, 1000 IU/m2 IV Day 16, Courses 1A \& 2A; Day 18, Course 1B; Day 17, Course 2B; Day 16, Maintenance, Month 1

Also known as: PEG-L-asparaginase, Oncaspar, PEG-asparaginase, pegasparagase

Chemotherapy for ALL

CTX DRUG

750 mg/m2 IV, days 1 \&15 for subjects \<40 year of age, substitute cyclophosphamide 500 mg/m2 IV over 60 minutes every 12 hours for 4 doses on days 15 \& 16 for subjects \< 40 years of age if day 14 bone marrow M2 or M3; Courses 1A \& 2A

Also known as: Cyclophosphamide, Cytoxan, Endoxan, Neosar, Procytox, Revimmune, cytophosphane, CPM, CYT

Chemotherapy for ALL

Prednisone DRUG

60 mg/m2 orally once daily on days 1-28 during Courses 1A \& 2A; Maintenance: Monthly, days 1-5

Also known as: Deltasone

Chemotherapy for ALL

Liposomal AraC DRUG

25 mg intrathecal (IT), on days 1 \& 15 during Courses 1A \& 2A; 50 mg intrathecal on day 1 during Maintenance Months 1 through 4

Also known as: Liposomal cytarabine, DepoCyt

Chemotherapy for ALL

MTX DRUG

220 mg/m2 IV bolus over 15 minutes then 60 mg/m2/hour for 36 hours once on days 2-3 and 16-17 during Courses 1B \& 2B; 20 mg/m2 orally one day per week every 7 days during Maintenance Months

Also known as: Methotrexate, Rheumatrex, Trexall

Chemotherapy for ALL

LCV DRUG

50 mg/m2 IV over 15-30 minutes every 6 hours for 3 doses to begin immediately after completion of methotrexate infusion, then 10 mg/m2 orally or IV over 15-30 minutes every 6 hours until methotrexate level less than 0.1 micromolar during Courses 1B \& 2B

Also known as: Leucovorin

Chemotherapy for ALL

AraC DRUG

2,000 mg/m2 IV, days 1-4 during Courses 1C \& 2C

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

Chemotherapy for ALL

Etoposide DRUG

500 mg/m2 IV over 3 hours once daily on days 1-4 during Courses 1C \& 2C

Also known as: VP-16, VePesid, Toposar

Chemotherapy for ALL

Dasatinib DRUG

140 mg orally daily if BCR/ABL positive and/or Ph+

Also known as: Sprycel

Chemotherapy for ALL

Rituximab DRUG

375 mg/m2 IV once daily on days 1 \& 15 (precursor B-cell ALL only, administer per institutional protocol) during Courses 1A, 1B, 1C \& 2A

Also known as: Rituxan

Chemotherapy for ALL

Hydrocortisone DRUG

Randomize patients proceeding to Course 1B to hydrocortisone versus placebo prior to PEG-asparaginase treatments in Courses 1B, 2B, 3B, and Maintenance month 1

Also known as: Hydrocortisone sodium succinate, Solu-Cortef

Chemotherapy for ALL

Eligibility Criteria

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

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent.
• Diagnosis of acute lymphoblastic leukemia or lymphoblastic lymphoma as defined by the World Health Organization \[94\]
• Untreated disease EXCEPT for corticosteroids, hydroxyurea, leukapheresis, and/or tyrosine kinase inhibitors for up to 2 weeks prior to initiation of study therapy.
• Age 18 through 60 years
• ECOG performance status 0,1, or 2 (see Appendix A)
• Adequate organ function defined as:
• Total bilirubin \< 2 mg/dL (unless due to ALL)
• AST(SGOT)/ALT(SGPT) \< 3 times institutional upper limit of normal (unless due to ALL)
• Serum creatinine \< 2 mg/dL (unless elevated creatinine felt by investigator to be acute and reversible) OR creatinine clearance \>60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
• Left ventricular ejection fraction ≥50%
• Women of child-bearing potential and men with partners of child- bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)

You may not qualify if:

• Current or anticipated use of other investigational agents during the study
• Known central nervous system mass lesion
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to liposomal cytarabine or other agents used in study inclusive of known allergy to polyethylene glycol.
• History of unprovoked venous thrombosis/thromboembolism
• Recurrent or chronic pancreatitis
• Uncontrolled diabetes mellitus
• Uncontrolled intercurrent illness that would limit compliance with study requirements including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or nursing.
• Any condition, in the opinion of the investigator, that compromises compliance with study requirements
• Known HIV positivity

Sponsors & Collaborators

• University of California, San Diego: lead
• Leadiant Biosciences, Inc.: collaborator

Study Sites (4)

UCSD, Division of Blood and Marrow Transplantation, Moores Cancer Center

La Jolla, California, 92093, United States

Location

Hematological Malignancies/Stem Cell Transplantation Unit, David Geffen School of Medicine at UCLA

Los Angeles, California, 90095, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

UCSF Comprehensive Cancer Center

San Francisco, California, 94143-0324, United States

Location

Related Publications (1)

• Linker C, Damon L, Ries C, Navarro W. Intensified and shortened cyclical chemotherapy for adult acute lymphoblastic leukemia. J Clin Oncol. 2002 May 15;20(10):2464-71. doi: 10.1200/JCO.2002.07.116.

  PMID: 12011123 RESULT

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Daunorubicin; Vincristine; pegaspargase; Cyclophosphamide; Prednisone; Methotrexate; Leucovorin; Cytarabine; Etoposide; Dasatinib; Rituximab; Hydrocortisone; hydrocortisone hemisuccinate

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Aminopterin; Pterins; Pteridines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Coenzymes; Enzymes and Coenzymes; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Thiazoles; Sulfur Compounds; Azoles; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• James K Mangan, MD, PhD

  UC San Diego, Division of Blood and Marrow Transplantation

  PRINCIPAL INVESTIGATOR

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: Associate Clinical Professor of Medicine

Study Record Dates

• First Submitted: January 21, 2014
• First Posted: January 23, 2014
• Study Start: January 1, 2014
• Primary Completion: April 14, 2022
• Study Completion: April 14, 2022
• Last Updated: May 2, 2022

Record last verified: 2022-04

Locations

US (4)