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

NCT ID: NCT01363128

Last Updated: 2021-05-03

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

72 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-07-12

Study Completion Date

2020-04-08

Brief Summary

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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.

Detailed Description

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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.

Conditions

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (hyper-CVAD, ofatumumab)

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.

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Given IV

Cytarabine

Intervention Type DRUG

Given IV

Dexamethasone

Intervention Type DRUG

Given IV or PO

Doxorubicin Hydrochloride

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Methotrexate

Intervention Type DRUG

Given IV

Ofatumumab

Intervention Type BIOLOGICAL

Given IV

Vincristine Sulfate

Intervention Type DRUG

Given IV

Interventions

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Cyclophosphamide

Given IV

Intervention Type DRUG

Cytarabine

Given IV

Intervention Type DRUG

Dexamethasone

Given IV or PO

Intervention Type DRUG

Doxorubicin Hydrochloride

Given IV

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Methotrexate

Given IV

Intervention Type DRUG

Ofatumumab

Given IV

Intervention Type BIOLOGICAL

Vincristine Sulfate

Given IV

Intervention Type DRUG

Other Intervention Names

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(-)-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 .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 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 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 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 Arzerra GSK1841157 HuMax-CD20 HuMax-CD20, 2F2 Kyocristine Leurocristine sulfate Leurocristine, sulfate Oncovin Vincasar Vincosid Vincrex Vincristine, sulfate

Eligibility Criteria

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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
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Elias Jabbour

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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M D Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

References

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Shi Z, Zhu Y, Zhang J, Chen B. Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia. Hematology. 2022 Dec;27(1):642-652. doi: 10.1080/16078454.2022.2074704.

Reference Type DERIVED
PMID: 35622074 (View on PubMed)

Sasaki K, Kantarjian HM, Morita K, Short NJ, Konopleva M, Jain N, Ravandi F, Garcia-Manero G, Wang S, Khoury JD, Jorgensen JL, Champlin RE, Khouri IF, Kebriaei P, Schroeder HM, Khouri M, Garris R, Takahashi K, O'Brien SM, Jabbour EJ. Hyper-CVAD plus ofatumumab versus hyper-CVAD plus rituximab as frontline therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: A propensity score analysis. Cancer. 2021 Sep 15;127(18):3381-3389. doi: 10.1002/cncr.33655. Epub 2021 Jun 17.

Reference Type DERIVED
PMID: 34138471 (View on PubMed)

Jabbour E, Richard-Carpentier G, Sasaki Y, Konopleva M, Patel K, Roberts K, Gu Z, Wang F, Huang X, Sasaki K, Short NJ, Jain N, Ravandi F, Daver NG, Kadia TM, Alvarado Y, DiNardo CD, Issa GC, Pemmaraju N, Garcia-Manero G, Verstovsek S, Wang S, Khoury JD, Jorgensen J, Champlin R, Khouri I, Kebriaei P, Schroeder H, Khouri M, Mullighan CG, Takahashi K, O'Brien SM, Kantarjian H. Hyper-CVAD regimen in combination with ofatumumab as frontline therapy for adults with Philadelphia chromosome-negative B-cell acute lymphoblastic leukaemia: a single-arm, phase 2 trial. Lancet Haematol. 2020 Jul;7(7):e523-e533. doi: 10.1016/S2352-3026(20)30144-7.

Reference Type DERIVED
PMID: 32589978 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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http://www.mdanderson.org

University of Texas MD Anderson Cancer Center Website

Other Identifiers

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NCI-2011-01061

Identifier Type: REGISTRY

Identifier Source: secondary_id

2010-0708

Identifier Type: OTHER

Identifier Source: secondary_id

2010-0708

Identifier Type: -

Identifier Source: org_study_id

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