Phase I/II Trial of R-CHOP + Azacytidine in Diffuse Large B Cell Lymphoma

• Sponsor: Weill Medical College of Cornell University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01004991
• Collaborator: Celgene (Industry)
• Enrollment: 14
• Location: 1
• Arm: 1
• Actual Duration (Months): 73
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B Cell Lymphoma	Biological: rituximab; Drug: cyclophosphamide; Drug: vincristine; Drug: doxorubicin; Drug: prednisone; Drug: azacytidine	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Trial of Azacytidine + R-CHOP in Diffuse Large B-Cell Lymphoma
• Actual Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Feb 1, 2016

Arms and Interventions

Arm

Intervention/Treatment

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

Biological: rituximab; 375 mg/m2 on Day 8 of each of 6 cycles; Drug: cyclophosphamide; 750 mg/m2 on Day 8 of each of 6 cycles; Drug: vincristine; 1.4 mg/m2 on Day 8 of each of 6 cycles; Drug: doxorubicin; 50 mg/m2 on Day 8 of each of 6 cycles; Drug: prednisone; 100 mg PO days 8-12 of each of 6 cycles; Drug: azacytidine; 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

Outcome Measures

Primary Outcome Measures

1. Complete Response [13 months]

   Complete Response

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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.

• Ability to understand and the willingness to sign a written informed consent document.

• ECOG performance status of 0-2

Exclusion Criteria:

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Weill Cornell Medical College	New York	New York	United States	10065

Sponsors and Collaborators

• Weill Medical College of Cornell University
• Celgene

Investigators

• Principal Investigator: Peter Martin, MD, Weill Medical College of Cornell University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT01004991
• Other Study ID Numbers: 0907010513
• First Posted: Oct 30, 2009
• Last Update Posted: Apr 10, 2017
• Last Verified: Feb 1, 2017

• Additional relevant MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Vincristine; Azacitidine

Study Results

Participant Flow

Arm/Group Title	All Patients
Arm/Group Description	subjects will receive azacytidine dose dependent on dose-escalation schedule at time of enrollment - all will receive standard dose RCHOP rituximab: 375 mg/m2 on Day 8 of each of 6 cycles cyclophosphamide: 750 mg/m2 on Day 8 of each of 6 cycles vincristine: 1.4 mg/m2 on Day 8 of each of 6 cycles doxorubicin: 50 mg/m2 on Day 8 of each of 6 cycles prednisone: 100 mg PO days 8-12 of each of 6 cycles azacytidine: 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
Period Title: Overall Study
STARTED	12
COMPLETED	12
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Patients
Arm/Group Description	subjects will receive azacytidine dose dependent on dose-escalation schedule at time of enrollment - all will receive standard dose RCHOP rituximab: 375 mg/m2 on Day 8 of each of 6 cycles cyclophosphamide: 750 mg/m2 on Day 8 of each of 6 cycles vincristine: 1.4 mg/m2 on Day 8 of each of 6 cycles doxorubicin: 50 mg/m2 on Day 8 of each of 6 cycles prednisone: 100 mg PO days 8-12 of each of 6 cycles azacytidine: 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
Overall Participants	12
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	65
Sex: Female, Male (Count of Participants)
Female	5 41.7%
Male	7 58.3%

Outcome Measures

1. Primary Outcome

Title	Complete Response
Description	Complete Response
Time Frame	13 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Patients
Arm/Group Description	subjects will receive azacytidine dose dependent on dose-escalation schedule at time of enrollment - all will receive standard dose RCHOP rituximab: 375 mg/m2 on Day 8 of each of 6 cycles cyclophosphamide: 750 mg/m2 on Day 8 of each of 6 cycles vincristine: 1.4 mg/m2 on Day 8 of each of 6 cycles doxorubicin: 50 mg/m2 on Day 8 of each of 6 cycles prednisone: 100 mg PO days 8-12 of each of 6 cycles azacytidine: 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
Measure Participants	12
Count of Participants [Participants]	11 91.7%

Adverse Events

Arm/Group Title	All Patients
Arm/Group Description	all study patients
All Cause Mortality
	All Patients
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	0/12 (0%)
Other (Not Including Serious) Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	12/12 (100%)
Blood and lymphatic system disorders
Neutropenia	12/12 (100%)
Neutropenic Fever	4/12 (33.3%)
thrombocytopenia	1/12 (8.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.