CClinicalTrials.gg
TerminatedNCT03488225Updated Jul 30, 2026Results posted

Combination Chemotherapy and Inotuzumab Ozogamicin in Treating Patients With B Acute Lymphoblastic Leukemia

A Phase 2 interventional study of Cyclophosphamide and Cytarabine in Acute Lymphoblastic Leukemia in Remission, B Acute Lymphoblastic Leukemia and B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative, sponsored by M.D. Anderson Cancer Center. Terminated at 1 site in United States. Open to participants aged 16 Years and older. Per ClinicalTrials.gov, last updated 2026-07-30.

Sponsored by M.D. Anderson Cancer Center · Phase 2, Interventional, and Treatment

Why this study was terminated
the study was closed early due to competing trials
Phase
Phase 2
Study type
Interventional
Enrollment
4
Allocation
Not applicable
Ages
16 Years and older
Sex
All
01

Study summary

This phase II trial studies how well combination chemotherapy and inotuzumab ozogamicin work in treating patients with B acute lymphoblastic leukemia. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone, methotrexate and cytarabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as inotuzumab ozogamicin, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving combination chemotherapy and inotuzumab ozogamicin may work better at treating B acute lymphoblastic leukemia.

Read the detailed description

PRIMARY OBJECTIVES:

I. To evaluate the clinical efficacy of the sequential combination of hyper-CVAD (hyperfractionated cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone, methotrexate and cytarabine) + inotuzumab ozogamicin in patients with newly diagnosed B-cell acute lymphocytic leukemia (ALL) in terms of event-free survival (EFS).

SECONDARY OBJECTIVES:

I. To evaluate other efficacy endpoints such as overall survival, overall response rate, minimal residual disease (MRD) negativity rate as well as the safety of this combination.

OUTLINE:

INTENSIVE CHEMOTHERAPY: Patients receive cyclophosphamide intravenously (IV) over 3 hours every 12 hours on days 1-3 and dexamethasone IV or orally (PO) on days 1-4 and 11-14 of courses 1 and 3. Patients may receive ofatumumab IV over 2 hours on days 1, 2 and 11 of course 1, days 1 and 8 of courses 2 and 4, and days 1 and 11 of course 3, or rituximab IV over 2 hours on days 1 and 11 of courses 1 and 3, and days 1 and 8 of courses 2 and 4. Patients also receive methotrexate intrathecally (IT) on day 2 of courses 1 and 3, IV over 24 hours on day 1 and IT on day 8 of courses 2 and 4, doxorubicin hydrochloride IV over 24 hours on day 4 of courses 1 and 3, vincristine sulfate IV over 1 hour on days 4 and 11 of courses 1 and 3, cytarabine IT on day 7 of courses 1 and 3, and IV over 2 hours every 12 hours on days 2 and 3, and IT on day 5 of courses 2 and 4, leucovorin calcium IV 4 times a days on day 2 of courses 2 and 4. Patients then receive inotuzumab ozogamicin IV over 1 hour on days 1 and 8 of courses 5-8. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive mercaptopurine PO thrice a day, methotrexate PO once a week, vincristine sulfate IV over 1 hour on day 1 and prednisone PO on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and every 6 months.

02

Conditions studied

  • Acute Lymphoblastic Leukemia in Remission
  • B Acute Lymphoblastic Leukemia
  • B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative

Browse trials for

03

Who can participate

Ages eligible
16 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Patients with newly diagnosed, previously untreated B-lineage ALL, or having achieved complete remission (CR) with one course of induction chemotherapy
  • Patients with extramedullary disease only are eligible
  • Failure to one induction course of chemotherapy (these patients will be analyzed separately)
  • Performance status of 0-3
  • Creatinine less than or equal to 2.0 mg/dL (unless considered tumor related)
  • Bilirubin less than or equal to 2.0 mg/dL (unless considered tumor related)
  • Adequate cardiac function as assessed by history and physical examination
  • No active or co-existing malignancy with life expectancy less than 12 months
  • Women of childbearing potential (WOCBP) or male subjects with a partner who is WOCBP must agree to use contraception during the study, if sexually active

Exclusion criteria

Exclusion Criteria:

  • Pregnant or nursing women
  • Known to be human immunodeficiency virus (HIV)-positive
  • Philadelphia chromosome (Ph)-positive 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 involvement or stable chronic liver disease per investigator assessment)
  • Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active hepatitis C
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
4 participants (actual)

Study arms

  • Experimental
    Treatment (hyper-CVAD, inotuzumab ozogamicin)

    See detailed description.

    Drug: Cyclophosphamide · Drug: Cytarabine · Drug: Dexamethasone · Drug: Doxorubicin Hydrochloride · Biological: Inotuzumab Ozogamicin · Other: Laboratory Biomarker Analysis · Drug: Leucovorin Calcium · Drug: Mercaptopurine · Drug: Methotrexate · Biological: Ofatumumab · Drug: Prednisone · Biological: Rituximab · Drug: Vincristine Sulfate

Interventions

  • DrugCyclophosphamide

    Given IV

    Also known as: (-)-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

  • DrugCytarabine

    Given IT or IV

    Also known as: .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

  • DrugDexamethasone

    Given IV or PO

    Also known as: 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

  • DrugDoxorubicin Hydrochloride

    Given IV

    Also known as: 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

  • BiologicalInotuzumab Ozogamicin

    Given IV

    Also known as: Besponsa, CMC-544, Way 207294, WAY-207294

  • OtherLaboratory Biomarker Analysis

    Correlative studies

  • DrugLeucovorin Calcium

    Given IV

    Also known as: Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate, Calcium Leucovorin, Calfolex, Calinat, Cehafolin, Citofolin, Citrec, citrovorum factor, Cromatonbic Folinico, Dalisol, Disintox, Divical, Ecofol, Emovis, Factor, Citrovorum, Flynoken A, Folaren, Folaxin, FOLI-cell, Foliben, Folidan, Folidar, Folinac, Folinate Calcium, folinic acid, Folinic Acid Calcium Salt Pentahydrate, Folinoral, Folinvit, Foliplus, Folix, Imo, Lederfolat, Lederfolin, Leucosar, leucovorin, Rescufolin, Rescuvolin, Tonofolin, Wellcovorin

  • DrugMercaptopurine

    Given PO

    Also known as: 3H-Purine-6-thiol, 6 MP, 6 Thiohypoxanthine, 6 Thiopurine, 6-Mercaptopurine, 6-Mercaptopurine Monohydrate, 6-MP, 6-Purinethiol, 6-Thiopurine, 6-Thioxopurine, 6H-Purine-6-thione, 1,7-dihydro- (9CI), 7-Mercapto-1,3,4,6-tetrazaindene, Alti-Mercaptopurine, Azathiopurine, BW 57-323H, Flocofil, Ismipur, Leukerin, Leupurin, Mercaleukim, Mercaleukin, Mercaptina, Mercaptopurinum, Mercapurin, Mern, NCI-C04886, Puri-Nethol, Purimethol, Purine, 6-mercapto-, Purine-6-thiol (8CI), Purine-6-thiol, monohydrate, Purinethiol, Purinethol, U-4748, WR-2785

  • DrugMethotrexate

    Given IT, IV or PO

    Also known as: 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

  • BiologicalOfatumumab

    Given IV

    Also known as: Arzerra, GSK1841157, HuMax-CD20, HuMax-CD20, 2F2

  • DrugPrednisone

    Given PO

    Also known as: .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisonum, Prednitone, Promifen, Servisone, SK-Prednisone

  • BiologicalRituximab

    Given IV

    Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, RTXM83

  • DrugVincristine Sulfate

    Given IV

    Also known as: Kyocristine, Leurocristine sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfate

05

What researchers measure

Primary outcomes

  1. Event-Free Survival

    Event-free survival defined as the time interval from date of treatment start until the date of death, disease progression or relapse.

    Time frame: Start of treatment up to 2 years

Secondary outcomes

  1. Overall Survival

    Time from date of treatment start until date of death due to any cause or last Follow-up.

    Time frame: Start of treatment up to 2 years

  2. Participants to Achieve Complete Remission (CR):

    Complete Remission (CR) is defined as - Normalization of the peripheral blood and bone marrow blasts \</= 5% in normocellular or hypercellular marrow, granulocyte count of 1x10\^9/L or above and platelets \>/= 100X10\^9/L and complete resolution of all sites of extramedullary disease.

    Time frame: Start of treatment up to 2 years

  3. Number of Participants With Minimal Residual Disease (MRD) Negativity

    MRD levels continuously assessed during induction and consolidation therapy by 6-color multiparameter flow. MRD negativity defined by a value of at least 10-4 and confirmed on a second bone marrow aspiration/biopsy performed after a subsequent cycle.

    Time frame: Start of treatment up to 2 years

  4. Number of Participants With Adverse Events

    For the purpose of toxicity monitoring, toxicities are defined as any treatment -related grade 3 or 4 non-hematologic AEs occurred any time during the trial.NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 utilized for adverse event reporting.

    Time frame: Start of treatment up to 30 days after last dose received.

06

Results

Posted Apr 13, 2021

Participant flow

Recruitment Period: March 2018 to January 2019

Participant flow — Overall Study
MilestoneTreatment (Hyper-CVAD, Inotuzumab Ozogamicin)
Started4
Completed0
Not completed4
Withdrew: Off protocol therapy2
Withdrew: Stem cell transplant2

Outcome measures

PrimaryEvent-Free Survival

Event-free survival defined as the time interval from date of treatment start until the date of death, disease progression or relapse.

Time frame:
Start of treatment up to 2 years
Reported as:
Median · Months
Event-Free Survival
MonthsTreatment (Hyper-CVAD, Inotuzumab Ozogamicin)
Event-Free Survival24 (18.5 to 24)
SecondaryOverall Survival

Time from date of treatment start until date of death due to any cause or last Follow-up.

Time frame:
Start of treatment up to 2 years
Reported as:
Median · Months
Overall Survival
MonthsTreatment (Hyper-CVAD, Inotuzumab Ozogamicin)
Overall Survival24 (18.5 to 24)
SecondaryParticipants to Achieve Complete Remission (CR):

Complete Remission (CR) is defined as - Normalization of the peripheral blood and bone marrow blasts \</= 5% in normocellular or hypercellular marrow, granulocyte count of 1x10\^9/L or above and platelets \>/= 100X10\^9/L and complete resolution of all sites of extramedullary disease.

Time frame:
Start of treatment up to 2 years
Reported as:
Count of participants · Participants
Participants to Achieve Complete Remission (CR):
ParticipantsTreatment (Hyper-CVAD, Inotuzumab Ozogamicin)
Participants to Achieve Complete Remission (CR):4
SecondaryNumber of Participants With Minimal Residual Disease (MRD) Negativity

MRD levels continuously assessed during induction and consolidation therapy by 6-color multiparameter flow. MRD negativity defined by a value of at least 10-4 and confirmed on a second bone marrow aspiration/biopsy performed after a subsequent cycle.

Time frame:
Start of treatment up to 2 years
Reported as:
Count of participants · Participants
Number of Participants With Minimal Residual Disease (MRD) Negativity
ParticipantsTreatment (Hyper-CVAD, Inotuzumab Ozogamicin)
Number of Participants With Minimal Residual Disease (MRD) Negativity4
SecondaryNumber of Participants With Adverse Events

For the purpose of toxicity monitoring, toxicities are defined as any treatment -related grade 3 or 4 non-hematologic AEs occurred any time during the trial.NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 utilized for adverse event reporting.

Time frame:
Start of treatment up to 30 days after last dose received.
Reported as:
Count of participants · Participants
Number of Participants With Adverse Events
ParticipantsTreatment (Hyper-CVAD, Inotuzumab Ozogamicin)
Neutropenic Fever2
Peripheral Sensory Neuropathy1
Allergic Reaction1
Muscle Weakness1

Adverse events

Collected over Up to 2 years. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Treatment (Hyper-CVAD, Inotuzumab Ozogamicin)0/4 (0%)3/4 (75%)4/4 (100%)
Most frequent serious events
Most frequent serious events
EventTreatment (Hyper-CVAD, Inotuzumab Ozogamicin)
Neutropenic FeverBlood and lymphatic system disorders2/4
FeverGeneral disorders2/4
Kidney InfectionInfections and infestations1/4
Muscle WeaknessMusculoskeletal and connective tissue disorders1/4
Most frequent other events
Showing 10 of 25
Most frequent other events
EventTreatment (Hyper-CVAD, Inotuzumab Ozogamicin)
Peripheral Sensory NeuropathyNervous system disorders4/4
HeadacheNervous system disorders3/4
NeutropeniaInvestigations3/4
Oral MucositisGastrointestinal disorders3/4
ThrombocytopeniaInvestigations3/4
Abdominal PainGastrointestinal disorders2/4
Alanine Aminotransferase IncreasedInvestigations2/4
Allergic ReactionImmune system disorders2/4
ConstipationGastrointestinal disorders2/4
Infusion Related ReactionGeneral disorders2/4

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Treatment (Hyper-CVAD, Inotuzumab Ozogamicin)
<=18 years0
Between 18 and 65 years4
>=65 years0
Age, Continuous
Age, Continuous(years)Treatment (Hyper-CVAD, Inotuzumab Ozogamicin)
Median29 (19 to 37)
Sex: Female, Male
Sex: Female, Male(Participants)Treatment (Hyper-CVAD, Inotuzumab Ozogamicin)
Female2
Male2
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Treatment (Hyper-CVAD, Inotuzumab Ozogamicin)
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White3
More than one race0
Unknown or Not Reported1
Region of Enrollment
Region of Enrollment(participants)Treatment (Hyper-CVAD, Inotuzumab Ozogamicin)
United States4
07

Study locations

1 site
  • M D Anderson Cancer Center
    Houston, Texas 77030, United States
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Aug 6, 2018

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03488225
Lead sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Apr 4, 2018
Start date
Mar 28, 2018
Primary completion
Apr 2, 2020
Completion
Apr 2, 2020
Results posted
Apr 13, 2021
Last update
Jul 30, 2026

Study contacts

Elias Jabbour
principal investigator · M.D. Anderson Cancer Center

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is terminated, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion