NCT01004991

Brief Summary

This is a phase I/II open label, multi-center study of azacytidine in combination with standard RCHOP therapy in patients with DLBCL. Patients will be treated with azacytidine at escalating doses on days 1-5, followed by standard dose rituximab plus CHOP chemotherapy on day 8, every 21 days. Patients will be treated for a total 6 cycles. The phase II portion will then evaluate efficacy of the combination at the established MTD.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
14

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jan 2010

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 29, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

October 30, 2009

Completed
2 months until next milestone

Study Start

First participant enrolled

January 1, 2010

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2013

Completed
2.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2016

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

April 10, 2017

Completed
Last Updated

April 10, 2017

Status Verified

February 1, 2017

Enrollment Period

3.7 years

First QC Date

October 29, 2009

Results QC Date

February 23, 2017

Last Update Submit

February 23, 2017

Conditions

Outcome Measures

Primary Outcomes (1)

  • Complete Response

    Complete Response

    13 months

Study Arms (1)

All patients

EXPERIMENTAL

subjects will receive azacytidine dose dependent on dose-escalation schedule at time of enrollment - all will receive standard dose RCHOP

Biological: rituximabDrug: cyclophosphamideDrug: vincristineDrug: doxorubicinDrug: prednisoneDrug: azacytidine

Interventions

rituximabBIOLOGICAL

375 mg/m2 on Day 8 of each of 6 cycles

All patients

750 mg/m2 on Day 8 of each of 6 cycles

All patients

1.4 mg/m2 on Day 8 of each of 6 cycles

All patients

50 mg/m2 on Day 8 of each of 6 cycles

All patients

100 mg PO days 8-12 of each of 6 cycles

All patients

Dose level 1: azacytidine 25 mg/m2 days 1-5 Dose level 2: azacytidine 50 mg/m2 days 1-5 Dose level 3: azacytidine 75 mg/m2 days 1-5

All patients

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients must have histologically confirmed DLBCL with characteristic immunophenotypic profiles. Tumor tissue must be confirmed to express the CD20 antigen by flow cytometry or immunohistochemistry.
  • Patients must have at least one site of measurable disease, 1.5 cm in diameter or greater.
  • Patient has not had any previous treatment.
  • Stage II (not appropriate for abbreviated chemoimmunotherapy and radiotherapy), III or IV disease
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Patients must have laboratory test results within these ranges:
  • Absolute neutrophil count \> = 1500/mm³
  • Platelet count \> = 75,000/mm³
  • Serum creatinine \< = 1.5X upper limit of normal (ULN)
  • Total bilirubin \< = 1.5X ULN. Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis.
  • AST (SGOT) and ALT (SGPT) \< = 2 x ULN
  • Disease free of prior malignancies for \> = 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
  • Women of childbearing potential must have a negative serum pregnancy test prior to azacitidine treatment.
  • Women of childbearing potential should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment with azacitidine. The effects of azacytidine on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Age \>18 years.
  • +2 more criteria

You may not qualify if:

  • Patients must not have any serious medical condition, laboratory abnormality,or psychiatric illness that would prevent the subject from signing the informed consent form.
  • Patients must not have any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
  • Use of any other experimental drug or therapy within 28 days of baseline.
  • Concurrent use of other anti-cancer agents or treatments.
  • Known positive for HIV or infectious hepatitis B.
  • Known central nervous system involvement by lymphoma.
  • Known or suspected hypersensitivity to azacitidine or mannitol.
  • Patients must not have advanced malignant hepatic tumors.
  • Pregnant and lactating women are excluded from the study because the risks to an unborn fetus or potential risks in nursing infants are unknown.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

RituximabCyclophosphamideVincristineDoxorubicinPrednisoneAzacitidine

Condition Hierarchy (Ancestors)

Lymphoma, B-CellLymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsVinca AlkaloidsSecologanin Tryptamine AlkaloidsIndole AlkaloidsAlkaloidsHeterocyclic CompoundsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingIndolizidinesIndolizinesDaunorubicinAnthracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicPolycyclic CompoundsAminoglycosidesGlycosidesCarbohydratesPregnadienediolsPregnadienesPregnanesSteroidsFused-Ring CompoundsAza CompoundsCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosides

Results Point of Contact

Title
Peter Martin, MD
Organization
Weill Cornell Medicine

Study Officials

  • Peter Martin, MD

    Weill Medical College of Cornell University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 29, 2009

First Posted

October 30, 2009

Study Start

January 1, 2010

Primary Completion

September 1, 2013

Study Completion

February 1, 2016

Last Updated

April 10, 2017

Results First Posted

April 10, 2017

Record last verified: 2017-02

Locations