Clinical Trial: NCT01363128 - My Cancer Genome

NCT01363128

Description:

This phase II trial studies how well combination chemotherapy and ofatumumab work in treating patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with ofatumumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving combination chemotherapy together with ofatumumab may be an effective treatment for acute lymphoblastic leukemia or lymphoblastic lymphoma.

Related Conditions:

Acute Lymphoblastic Leukemia
Burkitt Leukemia
Burkitt Lymphoma
Lymphoblastic Lymphoma

Recruiting Status:

Completed

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT01363128

Trial Eligibility

Document

Title

Brief Title: Combination Chemotherapy and Ofatumumab in Treating Patients With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma
Official Title: Phase II Study of the Hyper - CVAD Regimen in Combination With Ofatumumab as Frontline Therapy for Patients With CD-20 Positive Acute Lymphoblastic Leukemia

Clinical Trial IDs

ORG STUDY ID: 2010-0708
SECONDARY ID: NCI-2011-01061
SECONDARY ID: 2010-0708
SECONDARY ID: P30CA016672
NCT ID: NCT01363128

Conditions

Acute Lymphoblastic Leukemia
Adult Acute Lymphoblastic Leukemia in Complete Remission
Burkitt Leukemia
Burkitt Lymphoma
CD20 Positive
Childhood Acute Lymphoblastic Leukemia in Complete Remission
Lymphoblastic Lymphoma

Interventions

Drug	Synonyms	Arms
Cyclophosphamide	(-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719	Treatment (hyper-CVAD, ofatumumab)
Cytarabine	.beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453	Treatment (hyper-CVAD, ofatumumab)
Dexamethasone	Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, Visumetazone	Treatment (hyper-CVAD, ofatumumab)
Doxorubicin Hydrochloride	5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, hydroxydaunorubicin, Rubex	Treatment (hyper-CVAD, ofatumumab)
Methotrexate	Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, Lantarel, Ledertrexate, Lumexon, Maxtrex, Medsatrexate, Metex, Methoblastin, Methotrexate LPF, Methotrexate Methylaminopterin, Methotrexatum, Metotrexato, Metrotex, Mexate, Mexate-AQ, MTX, Novatrex, Rheumatrex, Texate, Tremetex, Trexeron, Trixilem, WR-19039	Treatment (hyper-CVAD, ofatumumab)
Ofatumumab	Arzerra, GSK1841157, HuMax-CD20, HuMax-CD20, 2F2	Treatment (hyper-CVAD, ofatumumab)
Vincristine Sulfate	Kyocristine, Leurocristine sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfate	Treatment (hyper-CVAD, ofatumumab)

Purpose

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the clinical efficacy of the combination of hyper-CVAD (cyclophosphamide,
      vincristine sulfate, doxorubicin hydrochloride, and dexamethasone) + ofatumumab in patients
      with newly diagnosed acute lymphoblastic leukemia with any level of CD20 expression:
      event-free survival; overall response rate; overall survival.

      SECONDARY OBJECTIVES:

      I. To evaluate the safety of this combination.

      OUTLINE:

      COURSES 1, 3, 5, 7: Patients receive hyper-CVAD comprising cyclophosphamide intravenously
      (IV) over 3 hours every 12 hours on days 1-3; doxorubicin hydrochloride IV over 24 hours on
      day 4; vincristine sulfate IV over 15 minutes on days 4 and 11; and dexamethasone IV over 30
      minutes or orally (PO) once daily (QD) on days 1-4 and 11-14. Patients also receive
      ofatumumab IV over 4-6 hours on days 1 and 11 of courses 1 and 3.

      COURSES 2, 4, 6, 8: Patients receive high-dose methotrexate IV over 2 hours and then over 22
      hours on day 1 and cytarabine IV over 2 hours every 12 hours on days 2-3. Patients also
      receive ofatumumab IV over 4-6 hours on days 1 and 8 of courses 2 and 4.

      Treatment repeats every 21-28 days for 8 courses in the absence of disease progression or
      unacceptable toxicity. Patients may receive maintenance therapy for an additional 30 months.

      After completion of study treatment, patients are followed up at 30 days and then every 3
      months for 1 year.

Trial Arms

Name	Type	Description	Interventions
Treatment (hyper-CVAD, ofatumumab)	Experimental	COURSES 1, 3, 5, 7: Patients receive hyper-CVAD comprising cyclophosphamide IV over 3 hours every 12 hours on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV over 15 minutes on days 4 and 11; and dexamethasone IV over 30 minutes or PO QD on days 1-4 and 11-14. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 11 of courses 1 and 3. COURSES 2, 4, 6, 8: Patients receive high-dose methotrexate IV over 2 hours and then over 22 hours on day 1 and cytarabine IV over 2 hours every 12 hours on days 2-3. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 8 of courses 2 and 4. Treatment repeats every 21-28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may receive maintenance therapy for an additional 30 months.	Cyclophosphamide Cytarabine Dexamethasone Doxorubicin Hydrochloride Methotrexate Ofatumumab Vincristine Sulfate

Eligibility Criteria

        Inclusion Criteria:

          -  Patients of all ages with newly diagnosed, previously untreated CD-20+ acute
             lymphoblastic leukemia (ALL), or lymphoblastic lymphoma, Burkitt leukemia/lymphoma or
             having achieved complete remission (CR) with one course of induction chemotherapy

          -  Failure to one induction course of chemotherapy (these patients will be analyzed
             separately)

          -  Performance status of 0, 1, or 2

          -  Creatinine less than or equal to 3.0 mg/dL (unless considered tumor related)

          -  Bilirubin less than or equal to 3.0 mg/dL (unless considered tumor related)

          -  Adequate cardiac function defined as no clinically significant history of arrhythmia
             as determined by the principal investigator (PI) and/or the treating physician,
             history of myocardial infarction (MI) or clinically significant abnormal
             electrocardiogram (EKG), as determined by the PI and/or the treating physician, within
             3 months prior to study enrollment; cardiac function will be assessed by history and
             physical examination

          -  No active or co-existing malignancy (other than ALL or lymphoblastic lymphoma) with
             life expectancy less than 12 months due to that malignancy

        Exclusion Criteria:

          -  Pregnant or nursing women

          -  Known to be human immunodeficiency virus positive (HIV+)

          -  Philadelphia chromosome (Ph)+ ALL

          -  Active and uncontrolled disease/infection as judged by the treating physician

          -  Unable or unwilling to sign the consent form

          -  Subjects who have current active hepatic or biliary disease (with exception of
             patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable
             chronic liver disease per investigator assessment)

          -  Treatment with any known non-marketed drug substance or experimental therapy within 5
             terminal half-lives (calculated by multiplying the reported terminal half-life by 5)
             or 4 weeks prior to enrollment, whichever is longer, or currently participating in any
             other interventional clinical study

          -  History of significant cerebrovascular disease in the past 6 months or ongoing event
             with active symptoms or sequelae

          -  Positive serology for hepatitis B (HB) defined as a positive test for hepatitis B
             surface antigen (HBsAg); in addition, if negative for HBsAg but hepatitis B core
             antibody (HBcAb) positive (regardless of HBsAb status), a HB deoxyribonucleic acid
             (DNA) test will be performed and if positive the subject will be excluded; consult
             with a physician experienced in care & management of subjects with hepatitis B to
             manage/treat subjects who are anti-HBc positive

          -  Positive serology for hepatitis C (HC) defined as a positive test for hepatitis C
             antibody (HCAb), in which case reflexively perform a HC radioimmunoblotting assay
             (RIBA) immunoblot assay on the same sample to confirm the result

Maximum Eligible Age:	N/A
Minimum Eligible Age:	N/A
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Event-free survival
Time Frame:	From the start of therapy until failure to respond, relapse or death, assessed up to 1 year
Safety Issue:
Description:	Will be monitored using the method of Thall et al. For continuous data, summary statistics including n, mean, standard deviation, median, minimum and maximum will be computed. The posterior median time to event and it 95% credible interval will be estimated. Kaplan-Meier method, Log rank test and Cox proportional hazards regression modeling will be utilized to analyze event free survival.

Secondary Outcome Measures

Measure:	Incidence of toxicity and adverse events
Time Frame:	Up to 30 days post-treatment
Safety Issue:
Description:	Toxicity will be monitored closely in all patients using the method of Thall et al. Descriptive statistics will include tabulations of frequencies.

Details

Phase:	Phase 2
Primary Purpose:	Interventional
Overall Status:	Completed
Lead Sponsor:	M.D. Anderson Cancer Center

Last Updated

July 27, 2020

Clinical Trials /

Combination Chemotherapy and Ofatumumab in Treating Patients With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma