S1312, Inotuzumab Ozogamicin and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Leukemia

NCT ID: NCT01925131

Last Updated: 2023-05-03

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-06-13

Study Completion Date

2023-01-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This phase I trial studies the side effects and best dose of inotuzumab ozogamicin when given together with combination chemotherapy in treating patients with relapsed or refractory acute leukemia. Immunotoxins, such as inotuzumab ozogamicin, can find cancer cells that express cluster of differentiation (CD)22 and kill them without harming normal cells. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving inotuzumab ozogamicin together with combination chemotherapy may kill more cancer cells.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

PRIMARY OBJECTIVES:

I. To assess the safety of inotuzumab ozogamicin in combination with cyclophosphamide, vincristine (vincristine sulfate) and prednisone (CVP) and to determine the maximum tolerated dose (MTD) of inotuzumab ozogamicin in this regimen for patients with relapsed or refractory CD22+ acute leukemia (B-cell acute lymphoblastic leukemia \[B-ALL\], mixed phenotype, and Burkitt's).

SECONDARY OBJECTIVES:

I. To estimate the preliminary activity (response rate: complete remission \[CR\] + complete remission with incomplete count recovery \[CRi\]) of this combination in the expansion cohort.

II. To estimate the frequency and severity of toxicities of this combination in this patient population.

OUTLINE: This is a dose-escalation study of inotuzumab ozogamicin.

Patients receive cyclophosphamide intravenously (IV) on day 1, vincristine sulfate IV on day 1, prednisone orally (PO) on days 1-5, and inotuzumab ozogamicin IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months for 1 year, every 3 months for 1 year, and then every 6 months for 1 year.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Acute Leukemias of Ambiguous Lineage B-cell Adult Acute Lymphoblastic Leukemia Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Burkitt Lymphoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 1

Combination chemotherapy and inotuzumab ozogamicin - Dose level 1 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and 0.4 mg/m2 inotuzumab ozogamicin IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

cyclophosphamide

Intervention Type DRUG

Given IV

vincristine sulfate

Intervention Type DRUG

Given IV

prednisone

Intervention Type DRUG

Given PO

inotuzumab ozogamicin

Intervention Type BIOLOGICAL

Given IV

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 2

Combination chemotherapy and inotuzumab ozogamicin - Dose level 2 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.6 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

cyclophosphamide

Intervention Type DRUG

Given IV

vincristine sulfate

Intervention Type DRUG

Given IV

prednisone

Intervention Type DRUG

Given PO

inotuzumab ozogamicin

Intervention Type BIOLOGICAL

Given IV

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 3

Combination chemotherapy and inotuzumab ozogamicin - Dose level 3 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

cyclophosphamide

Intervention Type DRUG

Given IV

vincristine sulfate

Intervention Type DRUG

Given IV

prednisone

Intervention Type DRUG

Given PO

inotuzumab ozogamicin

Intervention Type BIOLOGICAL

Given IV

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 4

Combination chemotherapy and inotuzumab ozogamicin - Dose level 4 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

cyclophosphamide

Intervention Type DRUG

Given IV

vincristine sulfate

Intervention Type DRUG

Given IV

prednisone

Intervention Type DRUG

Given PO

inotuzumab ozogamicin

Intervention Type BIOLOGICAL

Given IV

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 5

Combination chemotherapy and inotuzumab ozogamicin - Dose level 5 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

cyclophosphamide

Intervention Type DRUG

Given IV

vincristine sulfate

Intervention Type DRUG

Given IV

prednisone

Intervention Type DRUG

Given PO

inotuzumab ozogamicin

Intervention Type BIOLOGICAL

Given IV

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Treatment (combination chemotherapy and inotuzumab ozogamicin) - MTD

Combination chemotherapy and inotuzumab ozogamicin - Maximum Tolerated Dose Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

cyclophosphamide

Intervention Type DRUG

Given IV

vincristine sulfate

Intervention Type DRUG

Given IV

prednisone

Intervention Type DRUG

Given PO

inotuzumab ozogamicin

Intervention Type BIOLOGICAL

Given IV

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

cyclophosphamide

Given IV

Intervention Type DRUG

vincristine sulfate

Given IV

Intervention Type DRUG

prednisone

Given PO

Intervention Type DRUG

inotuzumab ozogamicin

Given IV

Intervention Type BIOLOGICAL

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

CPM CTX Cytoxan Endoxan Endoxana leurocristine sulfate VCR Vincasar PFS DeCortin Deltra CMC-544

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Patients must have a diagnosis of relapsed or refractory CD22-positive acute leukemia including B-ALL, mixed phenotype leukemia (biphenotypic), or Burkitt's leukemia based on World Health Organization (WHO) classification; patients with bilineal leukemia are excluded
* Patients must have evidence of acute leukemia in their peripheral blood or bone marrow; patients must have \>= 5% blasts in the peripheral blood or bone marrow within 14 days prior to registration; at least \>= 20% of those blasts must be CD22-positive (surface) based on local immunophenotyping and histopathology
* Patients must be refractory or have relapsed following prior induction therapy; a standard induction regimen is defined as any program of treatment that includes vincristine and prednisone or dexamethasone, cytarabine/anthracycline, or high dose cytarabine
* For sites with the B1931022 pharmaceutical trial open, precursor B-cell ALL patients from that site may be eligible for S1312 providing they meet the following criteria:

* Patient is in second salvage or more; OR
* Patient was treated on the standard of care arm of B1931022 and failed therapy
* Patients may have received prior allogeneic transplant or autologous transplant; however, patients with prior allogeneic bone marrow transplant will be eligible only if both of the following conditions are met:

* The transplant must have been performed \>= 90 days prior to registration
* The patient must not have \>= grade 2 acute graft versus host disease (GvHD) or either moderate or severe limited chronic GvHD within 14 days prior to registration
* Patients known to have Philadelphia chromosome positive (Ph+) ALL must have either failed treatment or been intolerant to treatment with at least two second or third generation tyrosine kinase inhibitors
* Patients must not have received prior treatment with inotuzumab ozogamicin; previous treatment with other anti-CD22 antibodies must have been completed at least 90 days prior to registration
* Patients must have Zubrod performance status 0-2
* Patients must not have received any chemotherapy, investigational agents, or undergone major surgery within 14 days prior to registration with the following exceptions:

* Monoclonal antibodies must not have been received for 1 week prior to registration
* Chimeric antigen receptor (CAR) T-cells must not have been received for 28 days prior to registration.
* Steroids, hydroxyurea, vincristine, 6-mercaptopurine, methotrexate, thioguanine and intrathecal chemotherapy are permitted within any time frame prior to registration. FDA-approved TKIs may also be administered until 1 day prior to start of study therapy (C1, D1).
* All drug-related toxicities must have resolved to =\< grade 2
* Patients must not have a systemic bacterial, fungal, or viral infection that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement despite appropriate antibiotics or other treatment)
* Patients must not have any other serious concurrent disease or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that would put the patient at undue risk of undergoing therapy
* Patients must not have active central nervous system (CNS) involvement (by clinical evaluation); patients with previous documented history of CNS involvement of acute leukemia, or with clinical signs or symptoms consistent with CNS involvement of acute leukemia, must have a lumbar puncture which is negative for CNS involvement of acute leukemia; the lumbar puncture must be completed within 14 days prior to registration; patients with no previous history of documented CNS involvement and with no clinical signs or symptoms consistent with CNS involvement are not required to have completed a lumbar puncture before registration; note that treatment with intrathecal therapy is recommended during protocol treatment but CNS analysis during treatment is not required
* Patients must have a peripheral blast count \< 25,000/uL within 2 days prior to registration; (treatment with hydroxyurea and steroids is permitted to bring the countdown)
* Patients must have serum creatinine =\< 2 x institutional upper limits of normal (IULN) within 7 days prior to registration
* Patients must have bilirubin =\< 2 x IULN within 7 days prior to registration (unless the bilirubin is primarily unconjugated)
* Patients must have \< grade 2 neuropathy (sensory/motor) within 7 days prior to registration
* Patients must have serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =\< 2.5 x IULN within 7 days prior to registration
* Patients with a history of a serious allergic or anaphylactic reaction to humanized monoclonal antibodies are not eligible
* Patients must not have a history of chronic or active hepatitis B or C infection; patients must have negative hepatitis B and C serologies performed within 28 days prior to registration
* Patients must not have evidence or history of veno-occlusive disease or sinusoidal obstruction syndrome
* Patients must not have a cardiac ejection fraction \< 45% or the presence of New York Heart Association stage III or IV heart failure within 14 days prior to registration; either echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) may be used to determine ejection fraction
* Patients must not have a myocardial infarction within 6 months prior to registration
* Patients must not have a history of clinically significant arrhythmia, prolonged corrected QT (QTc) interval, or unexplained syncope not thought to be vasovagal in nature within 6 months prior to registration
* Patients must not have a screening corrected QT using Fridericia's formula (QTcF) interval \> 500 milliseconds (by Fridericia calculation) based on the average of triplicate electrocardiogram (EKG) performed within 7 days prior to registration; note that triplicate EKG is required at other timepoints
* Patients must not have a history of chronic liver disease (or cirrhosis)
* Patients who are known to be human immunodeficiency virus (HIV)+ are eligible providing they meet all of the following additional criteria within 28 days prior to registration:

* CD4+ cells \>= 350/mm\^3 (nadir)
* Viral load of \< 50 copies HIV messenger ribonucleic acid (mRNA)/mm\^3 if on combination antiretroviral therapy (cART) or \< 25,000 copies HIV mRNA if not on cART
* No zidovudine or stavudine as part of cART Patients who are HIV+ and do not meet all of these criteria are not eligible for this study
* Patients with evidence of extramedullary disease at diagnosis will have computed tomography (CT) scan of the chest, abdomen and pelvis to obtain baseline values within 28 days prior to registration
* Patients must have complete history and physical examination within 28 days prior to registration
* Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
* Prior malignancy other than acute leukemia is allowed, provided it is in remission and there is no plan to treat the malignancy at the time of registration
* Pretreatment cytogenetics must be performed on all patients; collection of pretreatment specimens must be completed within 14 days prior to registration to S1312; specimens must be submitted to the site's preferred Clinical Laboratory Improvement Amendments (CLIA)-approved cytogenetics laboratory; reports of the results must be submitted as described; note that cytogenetics are required at other time points
* Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
* As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
* Patients planning to enroll in this study must first have a slot reserved in advance of the registration; all site staff will use OPEN to create a slot reservation
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Anjali Advani

Role: PRINCIPAL_INVESTIGATOR

SWOG Cancer Research Network

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

Stanford Cancer Institute Palo Alto

Palo Alto, California, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Ben Taub General Hospital

Houston, Texas, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

NCI-2013-01368

Identifier Type: REGISTRY

Identifier Source: secondary_id

S1312

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180888

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA032102

Identifier Type: NIH

Identifier Source: secondary_id

View Link

S1312

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

A Study of BN104 in the Treatment of Acute Leukemia
NCT06052813 ACTIVE_NOT_RECRUITING PHASE1/PHASE2