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AzTrials

Acute Lymphoblastic LeukemiaPhase 2NCT01363128

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

A Phase 2 study testing Cyclophosphamide, Cytarabine and Dexamethasone in people with Acute Lymphoblastic Leukemia and Adult Acute Lymphoblastic Leukemia in Complete Remission, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Any age
What is being tested?
Cyclophosphamide, Cytarabine and Dexamethasone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
72 participants
Where
1 siteUnited States
Study dates
12 Jul 2011to 8 Apr 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 10Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
Cyclophosphamide, Cytarabine, Dexamethasone, Doxorubicin Hydrochloride, Laboratory Biomarker Analysis
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Burkitt Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • CytarabineDrug

    Also called .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

    Given IV

  • DexamethasoneDrug

    Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex

    Given IV or PO

  • Doxorubicin HydrochlorideDrug

    Also called 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

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • MethotrexateDrug

    Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate

    Given IV

  • OfatumumabBiological

    Also called Arzerra, GSK1841157, HuMax-CD20, HuMax-CD20, 2F2

    Given IV

  • Vincristine SulfateDrug

    Also called Kyocristine, Leurocristine sulfate, Leurocristine, sulfate, Oncovin

    Given IV

Study groups in NCT01363128
Study groupRoleWhat they receive
Treatment (hyper-CVAD, ofatumumab)ExperimentalCOURSES 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.
Receives: Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Methotrexate; Biological: Ofatumumab; Drug: Vincristine Sulfate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Complete Remission (CR)

    Complete Remission is Normalization of the peripheral blood and bone marrow with 5% or less blasts in marrow with a granulocyte count of 1 x 109/L or above and a platelet count of 100x 109/L or above. Complete resolution of all sites of extramedullary disease is required for CR.

    Measured: Up to 8 years

  2. 4-Year Overall Survival

    Overall Survival is defined as time from date of treatment start until date of death due to any cause or last Follow-up. 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 survival at 4 years.

    Measured: Up to 4 years

  3. 4-year Event Free Survival

    Event Free Survival defined as the time from the start of therapy to time of primary refractory disease, relapse from CR, death from any cause or last follow-up. Kaplan-Meier method will be utilized to analyze event free survival for the 4 year percent alive and in CR.

    Measured: Up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Jun 2011 (estimated)
  2. Study start12 Jul 2011
  3. Primary completion8 Apr 2020
  4. Study completion8 Apr 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
72 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01363128
Sponsor's protocol ID
2010-0708
Other IDs
NCI-2011-01061, 2010-0708
Status last verified
Apr 2021
First submitted
27 May 2011
Last updated
3 May 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 35622074

  • 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.

    PubMed 34138471

  • 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.

    PubMed 32589978

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cyclophosphamide, Cytarabine and Dexamethasone in people with Acute Lymphoblastic Leukemia and Adult Acute Lymphoblastic Leukemia in Complete Remission, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Complete Remission (CR) (time frame: Up to 8 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01363128, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2021.

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