Trial Outcomes & Findings for Agatolimod Sodium, Rituximab, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Recurrent or Refractory Non-Hodgkin Lymphoma (NCT NCT00438880)

Last Updated: 2016-02-04

Results Overview

Participants will be treated in cohorts of 6 patients at each dose level of CpG 7909 (0.08 mg/kg, 0.16 mg/kg, 0.32 mg/kg, 0.48 mg/kg) and observed for at least 10 weeks post treatment. If at most one of the 6 patients experiences a dose limiting toxicity (DLT), a new cohort of 6 patients will be treated at the next higher dose level. A DLT for this study is defined as patients with one of the following: * Absolute neutrophil counts or platelet counts below 10\*10\^9/L for 14 days * Absolute neutrophil counts greater than 0.5 or less than 1\*10\^9/L * Platelet counts greater than 10 or less than 50\*10\^9/L for 28 days. * Any grade 3 non-hematologic toxicity not explainable by another obvious cause as assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. We are reporting the number of DLTs at each of the dose levels. The maximum tolerated dose will be 0.48 mg/kg or the largest dose level where 1 or fewer participants reports a dose limiting toxicity.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

38 participants

Primary outcome timeframe

at least 10 weeks post treatment up to 3 months.

Results posted on

2016-02-04

Participant Flow

Phase I of this study opened 10/20/2004 and accrued 30 patients before closing 10/29/2007. Eight patients were accrued to the Phase II portion at the maximum tolerated dose established in Phase I.

Participant milestones

Participant milestones
Measure	Phase I Phase I patients will receive the following treatment: * 250 mg/m\^2 Rituximab IV on days 1, 8, and 15 of a 27 day cycle * 5 mCi (Indium-111), 1.6 mg Ibritumomab IV on day 1 * 10 mCi (Indium-111), 1.6 mg Ibritumomab IV on day 8 * CpG 7909 (Agatolimod Sodium) doses will be assigned in groups of 6 patients. Dose levels will escalate in each group until maximum tolerability is attained (starting at 0.08 mg/kg and sequentially escalating to 0.16 mg/kg, 0.32 mg/kg, 0.48 mg/kg). Doses will be taken day 6, 13, 20, and 27 of a 27 day cycle. * 0.4 mCi/kg Yttrium-90 Zevalin IV on day 15	Phase II Phase II patients will receive the following treatment: * 250 mg/m\^2 Rituximab IV on days 1, 8, and 15 of a 27 day cycle * 5 mCi (Indium-111), 1.6 mg Ibritumomab IV on day 8 * 0.48 mg/kg CpG 7909 (Agatolimod Sodium) doses will be taken day 6, 13, 20, and 27 of a 27 day cycle. * 0.4 mCi/kg Yttrium-90 Zevalin IV on day 15
Overall Study STARTED	30	8
Overall Study COMPLETED	30	8
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Agatolimod Sodium, Rituximab, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Recurrent or Refractory Non-Hodgkin Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I n=30 Participants Phase I patients will receive the following treatment: * 250 mg/m\^2 Rituximab IV on days 1, 8, and 15 of a 27 day cycle * 5 mCi (Indium-111), 1.6 mg Ibritumomab IV on day 1 * 10 mCi (Indium-111), 1.6 mg Ibritumomab IV on day 8 * CpG 7909 (Agatolimod Sodium) doses will be assigned in groups of 6 patients. Dose levels will escalate in each group until maximum tolerability is attained (starting at 0.08 mg/kg and sequentially escalating to 0.16 mg/kg, 0.32 mg/kg, 0.48 mg/kg). Doses will be taken day 6, 13, 20, and 27 of a 27 day cycle. * 0.4 mCi/kg Yttrium-90 Zevalin IV on day 15	Phase II n=8 Participants Phase II patients will receive the following treatment: * 250 mg/m\^2 Rituximab IV on days 1, 8, and 15 of a 27 day cycle * 5 mCi (Indium-111), 1.6 mg Ibritumomab IV on day 8 * 0.48 mg/kg CpG 7909 (Agatolimod Sodium) doses will be taken day 6, 13, 20, and 27 of a 27 day cycle. * 0.4 mCi/kg Yttrium-90 Zevalin IV on day 15	Total n=38 Participants Total of all reporting groups
Age, Continuous	60.5 years n=5 Participants	68.5 years n=7 Participants	62.5 years n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	4 Participants n=7 Participants	17 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	4 Participants n=7 Participants	21 Participants n=5 Participants
Region of Enrollment United States	30 participants n=5 Participants	8 participants n=7 Participants	38 participants n=5 Participants

PRIMARY outcome

Timeframe: at least 10 weeks post treatment up to 3 months.

Population: Only participants accrued to the Phase I portion of this study were used to determine the maximum tolerated dose.

Outcome measures

Outcome measures
Measure	Phase I n=30 Participants Phase I patients will receive the following treatment: * 250 mg/m\^2 Rituximab IV on days 1, 8, and 15 of a 27 day cycle * 5 mCi (Indium-111), 1.6 mg Ibritumomab IV on day 1 * 10 mCi (Indium-111), 1.6 mg Ibritumomab IV on day 8 * CpG 7909 (Agatolimod Sodium) doses will be assigned in groups of 6 patients. Dose levels will escalate in each group until maximum tolerability is attained (starting at 0.08 mg/kg and sequentially escalating to 0.16 mg/kg, 0.32 mg/kg, 0.48 mg/kg). Doses will be taken day 6, 13, 20, and 27 of a 27 day cycle. * 0.4 mCi/kg Yttrium-90 Zevalin IV on day 15	Phase II Phase II patients will receive the following treatment: * 250 mg/m\^2 Rituximab IV on days 1, 8, and 15 of a 27 day cycle * 5 mCi (Indium-111), 1.6 mg Ibritumomab IV on day 8 * 0.48 mg/kg CpG 7909 (Agatolimod Sodium) doses will be taken day 6, 13, 20, and 27 of a 27 day cycle. * 0.4 mCi/kg Yttrium-90 Zevalin IV on day 15
Maximum Tolerated Dose of CpG 7909 as Determined Using the Number of Participants With a DLT at Each Dose Level Dose Level 1: (.08 mg/kg), n=6	0 participants	—
Maximum Tolerated Dose of CpG 7909 as Determined Using the Number of Participants With a DLT at Each Dose Level Dose Level 2: (.16 mg/kg), n=6	1 participants	—
Maximum Tolerated Dose of CpG 7909 as Determined Using the Number of Participants With a DLT at Each Dose Level Dose Level 3: (.32 mg/kg), n=6	0 participants	—
Maximum Tolerated Dose of CpG 7909 as Determined Using the Number of Participants With a DLT at Each Dose Level Dose Level 4: (.48 mg/kg), n=12	1 participants	—

PRIMARY outcome

Timeframe: Evaluations occur every three months up to a year

Population: Participants accrued to the Phase I portion of this study were not used to analyze the Phase II primary endpoint.

Complete Response (CR): * No measurable or nonmeasurable disease. * No symptoms of Lymphoma. * Non-palpable spleen, if palpable at baseline. * Histologically negative bone marrow, if positive at baseline. * All nodes \<1.5 cm in transverse diameter. Partial Response (PR): * greater than 50% decrease from baseline in the sum of the products of the longest perpendicular diameters of the six largest dominant lesions. * No new lesions We are reporting the number of participants that attained a status of CR or PR.

Outcome measures

Outcome measures
Measure	Phase I Phase I patients will receive the following treatment: * 250 mg/m\^2 Rituximab IV on days 1, 8, and 15 of a 27 day cycle * 5 mCi (Indium-111), 1.6 mg Ibritumomab IV on day 1 * 10 mCi (Indium-111), 1.6 mg Ibritumomab IV on day 8 * CpG 7909 (Agatolimod Sodium) doses will be assigned in groups of 6 patients. Dose levels will escalate in each group until maximum tolerability is attained (starting at 0.08 mg/kg and sequentially escalating to 0.16 mg/kg, 0.32 mg/kg, 0.48 mg/kg). Doses will be taken day 6, 13, 20, and 27 of a 27 day cycle. * 0.4 mCi/kg Yttrium-90 Zevalin IV on day 15	Phase II n=8 Participants Phase II patients will receive the following treatment: * 250 mg/m\^2 Rituximab IV on days 1, 8, and 15 of a 27 day cycle * 5 mCi (Indium-111), 1.6 mg Ibritumomab IV on day 8 * 0.48 mg/kg CpG 7909 (Agatolimod Sodium) doses will be taken day 6, 13, 20, and 27 of a 27 day cycle. * 0.4 mCi/kg Yttrium-90 Zevalin IV on day 15
Tumor Response Complete Response (CR)	—	1 participants
Tumor Response Partial Response (PR)	—	0 participants

SECONDARY outcome

Timeframe: Up to 1 year from treatment start date

Population: Only participants accrued to the Phase II portion of the study were evaluated for this endpoint.

The Progression-free survival (PFS) is defined as the time from registration to progression or death due to any cause. The distribution of PFS will be estimated using the method of Kaplan-Meier.

Outcome measures

Outcome measures
Measure	Phase I Phase I patients will receive the following treatment: * 250 mg/m\^2 Rituximab IV on days 1, 8, and 15 of a 27 day cycle * 5 mCi (Indium-111), 1.6 mg Ibritumomab IV on day 1 * 10 mCi (Indium-111), 1.6 mg Ibritumomab IV on day 8 * CpG 7909 (Agatolimod Sodium) doses will be assigned in groups of 6 patients. Dose levels will escalate in each group until maximum tolerability is attained (starting at 0.08 mg/kg and sequentially escalating to 0.16 mg/kg, 0.32 mg/kg, 0.48 mg/kg). Doses will be taken day 6, 13, 20, and 27 of a 27 day cycle. * 0.4 mCi/kg Yttrium-90 Zevalin IV on day 15	Phase II n=8 Participants Phase II patients will receive the following treatment: * 250 mg/m\^2 Rituximab IV on days 1, 8, and 15 of a 27 day cycle * 5 mCi (Indium-111), 1.6 mg Ibritumomab IV on day 8 * 0.48 mg/kg CpG 7909 (Agatolimod Sodium) doses will be taken day 6, 13, 20, and 27 of a 27 day cycle. * 0.4 mCi/kg Yttrium-90 Zevalin IV on day 15
Progression-free Survival	—	1.57 months Interval 1.22 to 3.42

SECONDARY outcome

Timeframe: Up to 1 year from treatment start date

Population: The duration of response was not analyzed due to a lack of more than one response.

Duration of response (DoR) will be calculated from the documentation of response until the date of progression in the subset of patients who respond.

Outcome measures

Outcome data not reported

Adverse Events

Phase I

Serious events: 14 serious events

Other events: 30 other events

Deaths: 0 deaths

Phase II

Serious events: 5 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Phase I n=30 participants at risk Phase I patients will receive the following treatment: * 250 mg/m\^2 Rituximab IV on days 1, 8, and 15 of a 27 day cycle * 5 mCi (Indium-111), 1.6 mg Ibritumomab IV on day 1 * 10 mCi (Indium-111), 1.6 mg Ibritumomab IV on day 8 * CpG 7909 (Agatolimod Sodium) doses will be assigned in groups of 6 patients. Dose levels will escalate in each group until maximum tolerability is attained (starting at 0.08 mg/kg and sequentially escalating to 0.16 mg/kg, 0.32 mg/kg, 0.48 mg/kg). Doses will be taken day 6, 13, 20, and 27 of a 27 day cycle. * 0.4 mCi/kg Yttrium-90 Zevalin IV on day 15	Phase II n=8 participants at risk Phase II patients will receive the following treatment: * 250 mg/m\^2 Rituximab IV on days 1, 8, and 15 of a 27 day cycle * 5 mCi (Indium-111), 1.6 mg Ibritumomab IV on day 8 * 0.48 mg/kg CpG 7909 (Agatolimod Sodium) doses will be taken day 6, 13, 20, and 27 of a 27 day cycle. * 0.4 mCi/kg Yttrium-90 Zevalin IV on day 15
Blood and lymphatic system disorders Febrile neutropenia	3.3% 1/30 • Number of events 1	0.00% 0/8
Gastrointestinal disorders Constipation	0.00% 0/30	12.5% 1/8 • Number of events 1
Investigations Leukocyte count decreased	23.3% 7/30 • Number of events 7	0.00% 0/8
Investigations Neutrophil count decreased	33.3% 10/30 • Number of events 11	12.5% 1/8 • Number of events 1
Investigations Platelet count decreased	40.0% 12/30 • Number of events 20	50.0% 4/8 • Number of events 7
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	0.00% 0/30	12.5% 1/8 • Number of events 1

Other adverse events

Other adverse events
Measure	Phase I n=30 participants at risk Phase I patients will receive the following treatment: * 250 mg/m\^2 Rituximab IV on days 1, 8, and 15 of a 27 day cycle * 5 mCi (Indium-111), 1.6 mg Ibritumomab IV on day 1 * 10 mCi (Indium-111), 1.6 mg Ibritumomab IV on day 8 * CpG 7909 (Agatolimod Sodium) doses will be assigned in groups of 6 patients. Dose levels will escalate in each group until maximum tolerability is attained (starting at 0.08 mg/kg and sequentially escalating to 0.16 mg/kg, 0.32 mg/kg, 0.48 mg/kg). Doses will be taken day 6, 13, 20, and 27 of a 27 day cycle. * 0.4 mCi/kg Yttrium-90 Zevalin IV on day 15	Phase II n=8 participants at risk Phase II patients will receive the following treatment: * 250 mg/m\^2 Rituximab IV on days 1, 8, and 15 of a 27 day cycle * 5 mCi (Indium-111), 1.6 mg Ibritumomab IV on day 8 * 0.48 mg/kg CpG 7909 (Agatolimod Sodium) doses will be taken day 6, 13, 20, and 27 of a 27 day cycle. * 0.4 mCi/kg Yttrium-90 Zevalin IV on day 15
Blood and lymphatic system disorders Hemoglobin decreased	63.3% 19/30 • Number of events 40	100.0% 8/8 • Number of events 15
Cardiac disorders Arrhythmia	0.00% 0/30	12.5% 1/8 • Number of events 1
Gastrointestinal disorders Abdominal pain	3.3% 1/30 • Number of events 1	0.00% 0/8
Gastrointestinal disorders Diarrhea	0.00% 0/30	12.5% 1/8 • Number of events 1
Gastrointestinal disorders Nausea	3.3% 1/30 • Number of events 1	0.00% 0/8
General disorders Chills	3.3% 1/30 • Number of events 1	0.00% 0/8
General disorders Fatigue	6.7% 2/30 • Number of events 5	12.5% 1/8 • Number of events 1
General disorders Localized edema	3.3% 1/30 • Number of events 1	0.00% 0/8
General disorders Pain	3.3% 1/30 • Number of events 1	0.00% 0/8
Infections and infestations Abdominal infection	0.00% 0/30	12.5% 1/8 • Number of events 1
Infections and infestations Sinusitis	10.0% 3/30 • Number of events 3	0.00% 0/8
Investigations Alanine aminotransferase increased	0.00% 0/30	12.5% 1/8 • Number of events 1
Investigations Blood bilirubin increased	0.00% 0/30	12.5% 1/8 • Number of events 1
Investigations Leukocyte count decreased	86.7% 26/30 • Number of events 63	50.0% 4/8 • Number of events 7
Investigations Neutrophil count decreased	76.7% 23/30 • Number of events 37	50.0% 4/8 • Number of events 5
Investigations Platelet count decreased	86.7% 26/30 • Number of events 34	62.5% 5/8 • Number of events 7
Metabolism and nutrition disorders Anorexia	0.00% 0/30	12.5% 1/8 • Number of events 1
Metabolism and nutrition disorders Blood glucose increased	3.3% 1/30 • Number of events 1	0.00% 0/8
Musculoskeletal and connective tissue disorders Neck pain	3.3% 1/30 • Number of events 1	0.00% 0/8
Nervous system disorders Neurological disorder NOS	3.3% 1/30 • Number of events 1	0.00% 0/8
Nervous system disorders Syncope vasovagal	0.00% 0/30	12.5% 1/8 • Number of events 1
Skin and subcutaneous tissue disorders Petechiae	3.3% 1/30 • Number of events 1	0.00% 0/8
Skin and subcutaneous tissue disorders Rash desquamating	13.3% 4/30 • Number of events 4	0.00% 0/8
Skin and subcutaneous tissue disorders Sweating	3.3% 1/30 • Number of events 1	0.00% 0/8
Vascular disorders Hypotension	3.3% 1/30 • Number of events 1	12.5% 1/8 • Number of events 1

Additional Information

Thomas E. Witzig, M.D.

Mayo Clinic Cancer Center

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place