Phase II Study of ONTAK in Previously Treated Patients With Low-grade Non-Hodgkin's Lymphoma (NHL)

• Sponsor: Eisai Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00051025
• Collaborator: (none)
• Enrollment: 9
• Locations: 2
• Duration (Months): 76
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to look at the safety and effectiveness of ONTAK in previously treated patients with NHL.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin's Lymphoma; Lymphoma, B-cell; Lymphoma, Low-grade	Drug: ONTAK	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: A Randomized, Multicenter, Phase II Evaluation of ONTAK (Denileukin Diftitox) in Patients With Previously Treated, Indolent, B-Cell, Non-Hodgkin's Lymphoma
• Study Start Date: May 1, 2000
• Actual Primary Completion Date: Jan 1, 2001
• Actual Study Completion Date: Sep 1, 2006

Outcome Measures

Primary Outcome Measures

1. Objective Clinical Response: Complete Response (CR) or Partial Response (PR) at Week 24, or, in the Event of Lengthened Cycle Intervals, at the End of Cycle 8. [24 Weeks]

   Complete response: achievement of a complete regression for >4 weeks of all palpable and x-ray demonstrable disease and bone marrow disease. Partial response: response to therapy with a 75% reduction in the greatest diameters of the measurable lesions for >4 weeks and had indeterminate bone marrow biopsy

Secondary Outcome Measures

1. Duration of Response [From beginning of response to time of relapse]

   The duration of response was defined as the time interval from start of the first response (CR or PR) to the time of documented disease progression.

2. Time-to-Treatment Failure [From start of first treatment]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Pathological diagnosis of low-grade (indolent), B-cell, non-Hodgkin's lymphoma.

• Positive expression for CD25 of tumor cells in a lymph node biopsy as defined by greater than 20% of malignant cells staining for CD25 by standardized immunohistochemical assay.

• Modified Ann Arbor Stage I, II, III or IV.

• Patients must have received at least two but no more than five prior therapies. One prior therapy must have been cytotoxic chemotherapy and one prior therapy must have been monoclonal antibody therapy. Combination chemotherapy, including regimens used prior to bone marrow transplantation, will count as a single therapy for purposes of eligibility.

• Patients must have bidimensionally measurable disease.

• Patients must be 18 years of age or older.

• An ECOG performance status of 0, 1, or 2.

• Acceptable organ function defined as follows:

• absolute neutrophil count (ANC) > or = to 1,000/mm3, platelet count > or = to 50,000/mm3, Hemoglobin > or = to 8 g/dL;

• Bilirubin < or = to 1.5 times the upper limit of normal (ULN);

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < or = to 1.5 times the upper limit of normal;

• Serum creatinine <1.8mg/dL;

• Serum albumin > or = to 3.0 g/dL.

• New York Heart Association classification of I or II and no history of poorly controlled hypertension.

• Must be free of serious concurrent illness.

• Female patients must meet the following criteria:

• If the patient is a female of childbearing potential, she must have negative serum beta human chorionic gonadotropin (B-hCG) pregnancy test within seven days prior to study entry and must have used an effective means of contraception or have been sexually abstinent for at least four weeks prior to the negative serum pregnancy test and through to study entry.

• Female patients of childbearing potential must agree to practice an effective method of birth control during the entire treatment period and for at least three weeks after their last treatment on protocol.

Exclusion Criteria:

• Patients with cutaneous T-cell lymphoma.

• Patients previously treated with ONTAK (DAB389lL-2) or DAB486IL-2.

• Inability to comply with protocol requirements for this study.

• Pregnant women or lactating women who are breast feeding or women planning to become pregnant during the treatment period or three weeks after their last treatment on protocol.

• Serious intercurrent medical illnesses or active infections requiring parenteral antibiotics, which would interfere with the ability of the patient to carry out the treatment program.

• Sero-positive for human immunodeficiency virus (HIV) antibody. History of ongoing Hepatitis B or Hepatitis C infection.

• Another malignancy or history of another cancer with less than five disease-free years (other than resected basal or squamous cell skin cancers or in situ cervical cancer).

• Patients with a known hypersensitivity to ONTAK or any of its components: diphtheria toxin, interleukin-2, or excipients.

• Any investigational agents within one month prior to study entry.

• Prior radiation therapy within four weeks of enrollment or to the only site of evaluable disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Central Baptist Hospital	Lexington	Kentucky	United States	40503
2	Hematology and Oncology Services	Metairie	Louisiana	United States	70006

Sponsors and Collaborators

• Eisai Inc.

Investigators

• Study Director: Elyane Lombardy, M.D., Ligand Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00051025
• Other Study ID Numbers: L4389-30; NCT00005621
• First Posted: Jan 3, 2003
• Last Update Posted: Jul 13, 2012
• Last Verified: Jul 1, 2012

• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell

Study Results

Participant Flow

Recruitment Details	This study was recruited at 6 centers in U.S. during the period of 18-May-2000 to 12-May-2001

Arm/Group Title	Ontak 4-Course Group	Ontak 8-Course Group
Arm/Group Description	Four courses of Ontak 9 mcg/kg/day for 5 consecutive days every 21 days	Eight courses of Ontak 9 mcg/kg/day for 5 consecutive days every 21 days
Period Title: Overall Study
STARTED	5	4
COMPLETED	3	0
NOT COMPLETED	2	4

Baseline Characteristics

Arm/Group Title	Ontak 4-Course Group	Ontak 8-Course Group	Total
Arm/Group Description	Four courses of Ontak 9 mcg/kg/day for 5 consecutive days every 21 days	Eight courses of Ontak 9 mcg/kg/day for 5 consecutive days every 21 days	Total of all reporting groups
Overall Participants	5	4	9
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	3 60%	2 50%	5 55.6%
>=65 years	2 40%	2 50%	4 44.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.4 (8.4)	60.8 (15.5)	63.3 (11.5)
Sex: Female, Male (Count of Participants)
Female	3 60%	1 25%	4 44.4%
Male	2 40%	3 75%	5 55.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 25%	1 11.1%
White	5 100%	3 75%	8 88.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	5 100%	4 100%	9 100%

Outcome Measures

1. Primary Outcome

Title	Objective Clinical Response: Complete Response (CR) or Partial Response (PR) at Week 24, or, in the Event of Lengthened Cycle Intervals, at the End of Cycle 8.
Description	Complete response: achievement of a complete regression for >4 weeks of all palpable and x-ray demonstrable disease and bone marrow disease. Partial response: response to therapy with a 75% reduction in the greatest diameters of the measurable lesions for >4 weeks and had indeterminate bone marrow biopsy
Time Frame	24 Weeks

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Ontak 4-Course Group	Ontak 8-Course Group
Arm/Group Description	Four courses of Ontak 9 mcg/kg/day for 5 consecutive days every 21 days	Eight courses of Ontak 9 mcg/kg/day for 5 consecutive days every 21 days
Measure Participants	5	4
Number [Participants]	1 20%	1 25%

2. Secondary Outcome

Title	Duration of Response
Description	The duration of response was defined as the time interval from start of the first response (CR or PR) to the time of documented disease progression.
Time Frame	From beginning of response to time of relapse

Outcome Measure Data

Analysis Population Description

Intent-to-treat. Please note: Data represent 1 subject in each treatment group who responded.

Arm/Group Title	Ontak 4-Course Group	Ontak 8-Course Group
Arm/Group Description	Four courses of Ontak 9 mcg/kg/day for 5 consecutive days every 21 days	Eight courses of Ontak 9 mcg/kg/day for 5 consecutive days every 21 days
Measure Participants	1	1
Number [Days]	175	797

3. Secondary Outcome

Title	Time-to-Treatment Failure
Time Frame	From start of first treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Ontak 4-Course Group		Ontak 8-Course Group
Arm/Group Description	Four courses of Ontak 9 mcg/kg/day for 5 consecutive days every 21 days		Eight courses of Ontak 9 mcg/kg/day for 5 consecutive days every 21 days
All Cause Mortality
	Ontak 4-Course Group		Ontak 8-Course Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ontak 4-Course Group		Ontak 8-Course Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/5 (20%)		1/4 (25%)
Gastrointestinal disorders
Abdominal Pain	0/5 (0%)		1/4 (25%)
General disorders
Chest Pain	0/5 (0%)		1/4 (25%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Progression of Mantle Cell Lymphoma	0/5 (0%)		1/4 (25%)
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	1/5 (20%)		0/4 (0%)
Respiratory Failure	1/5 (20%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Ontak 4-Course Group		Ontak 8-Course Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		4/4 (100%)
Cardiac disorders
Tachycardia	1/5 (20%)		2/4 (50%)
Gastrointestinal disorders
Abdominal Distention	1/5 (20%)		1/4 (25%)
Abdominal Pain	0/5 (0%)		2/4 (50%)
Diarrhea	0/5 (0%)		2/4 (50%)
Lip Blister	1/5 (20%)		1/4 (25%)
Nausea	3/5 (60%)		2/4 (50%)
Vomiting	1/5 (20%)		1/4 (25%)
General disorders
Asthenia	1/5 (20%)		1/4 (25%)
Chest Discomfort	0/5 (0%)		2/4 (50%)
Fatigue	3/5 (60%)		3/4 (75%)
Oedema Peripheral	2/5 (40%)		1/4 (25%)
Pain	1/5 (20%)		2/4 (50%)
Pyrexia	2/5 (40%)		2/4 (50%)
Metabolism and nutrition disorders
Anorexia	1/5 (20%)		1/4 (25%)
Musculoskeletal and connective tissue disorders
Back Pain	1/5 (20%)		1/4 (25%)
Pain in Extremity	1/5 (20%)		1/4 (25%)
Nervous system disorders
Headache	0/5 (0%)		2/4 (50%)
Psychiatric disorders
Insomnia	2/5 (40%)		2/4 (50%)
Respiratory, thoracic and mediastinal disorders
Cough	1/5 (20%)		1/4 (25%)
Dyspnea	3/5 (60%)		0/4 (0%)
Skin and subcutaneous tissue disorders
Rash	2/5 (40%)		1/4 (25%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.