A Phase 2 Clinical Trial of Rituxan and B-Glucan PGG in Relapsed Indolent Non-Hodgkin Lymphoma

• Sponsor: Dana-Farber Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT02086175
• Collaborator: HiberCell, Inc. (Industry)
• Enrollment: 25
• Location: 1
• Arm: 1
• Actual Duration (Months): 74.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This research study is evaluating a drug combination called Imprime PGG and Rituximab as a possible treatment for relapsed/refractory indolent B cell non-Hodgkin lymphomas (NHL).

Condition or Disease	Intervention/Treatment	Phase
Relapsed/Refractory Indolent B Cell Non-Hodgkin Lymphomas	Drug: Imprime PGG; Drug: Rituximab	Phase 2

Detailed Description

After the screening procedures confirms eligibility:

Study Drugs: The participant will receive both Imprime PGG and rituximab weekly, for four weeks.

Clinical Exams: At the participant's weekly visit there will be have a physical exam and general health and specific questions about any problems they might be having and any medications the participant may be taking.

Scans (or Imaging tests):The Investigator will measure the participant's tumor 10 weeks after Week 4 of treatment by CT scan. Additional scans will be performed at 6 months and 12 months following the end of treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Clinical Trial of Rituxan and B-Glucan PGG in Relapsed Indolent Non-Hodgkin Lymphoma
• Actual Study Start Date: Dec 1, 2014
• Actual Primary Completion Date: Oct 11, 2018
• Actual Study Completion Date: Feb 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Imprime PGG and Rituximab The study drug, Imprime PGG, will be administered intravenously at a dose of 4mg/kg weekly for 4 weeks. Rituximab will be administered intravenously by institutional standards concurrently at a dose of 375mg/m2 weekly for 4 weeks. Response will be assessed with CT scans 10 weeks +/- 3 days following the completion of treatment	Drug: Imprime PGG; Drug: Rituximab; Other Names: IDEC-102 IDEC-C2B8 Rituxan Mabthera

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate [Response assessed at week 14 of study calendar (10 weeks after the 4-week treatment regimen).]

   Overall response rate is percentage of participants with complete (CR) and partial (PR) responses as best response during treatment. CR: Nodal Masses: For FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative For variably FDG-avid or PET negative; regression to normal size on CT. Liver/Spleen: No palpable nodules -Bone Marrow Infiltrate cleared on repeat biopsy; if indeterminate by morphology, immunohistochemistry should be negative. PR: Nodal Masses: 50% decrease in SPD of up to 6 largest dominant masses; no increase in size of other nodes. FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site. Variably FDG-avid or PET negative; regression on CT. Liver/Spleen: 50% decrease in SPD of nodules; no increase in size of liver or spleen. Bone Marrow: Irrelevant if positive prior to therapy; cell type should be specified.

Secondary Outcome Measures

1. Median Progression-free Survival (PFS) [Patients were followed for a median (range) of 13.6 months (3-25).]

   Progression free survival (PFS) is defined as the time from start of treatment to disease progression or death from any cause as estimated by Kaplan Meier methods. Patients who have not progressed and are alive are censored at the date the patient is known to be progression-free. Response is measure using the International Harmonization Project for Lymphoma criteria Cheson 2007, using CT scans of the chest, abdomen, and pelvis.

2. Duration of Response (DOR) [Patients were followed for a median (range) of 13.6 months (3-25).]

   Duration of response DR is defined as the time from the date of first response (complete or partial) after treatment to the date of disease progression or death for any cause. Patients who are alive without progression are censored at the date the patient is last know to be progression-free.

3. Imprime PGG-bound Neutrophils Status by Response [Up to 14 weeks with a median (range of) 13 weeks (12-14).]

   Imprime PGG-bound neutrophils analyzed using established methods (peripheral blood samples and post-treatment tumor samples to quantify the binding of Imprime PGG to neutrophils) by treatment response, best response.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Participants must meet the following criteria on screening examination to be eligible to participate in the study:

• Patients must have histologically determined indolent NHL that is relapsed or primary refractory after initial therapy. Indolent NHL includes the morphologic and clinical variants:

• Follicular lymphoma, grades 1-3a

• Marginal zone lymphoma (extranodal, nodal, or splenic)

• All nodal marginal zone lymphomas are eligible

• Extranodal marginal zone lymphomas of the stomach (gastric MALT lymphomas) may not be candidates for cure with antibiotics or local radiotherapy. Patients who have failed antibiotics or local therapy are eligible for the protocol as long as they have measurable disease and are naïve to chemotherapy and monoclonal antibody therapy.

• Splenic marginal zone lymphoma patients may have received prior splenectomy as long as they have measurable disease and are naïve to chemotherapy and monoclonal antibody therapy.

• Re-biopsy is not mandated at relapse unless there is clinical suspicion about an alternate diagnosis.

• Between 1-3 prior lines of chemoimmunotherapy and/or monotherapy with rituximab. Patients may not have had prior autologous or allogeneic stem cell transplantation.

• Measurable disease that has not been previously irradiated on CT scans of at least 2 cm, OR if the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation. Imaging must be completed no greater than 4 weeks prior to study enrollment.

• ECOG performance status 0-2 (Appendix B, Section 17.2)

• Absolute neutrophil count ≥1000 prior to treatment

• Oxygen saturation ≥ 90%, no more than 2 LPM oxygen

• Serum creatinine ≤ 1.5 X ULN

• AST ≤ 3 X ULN

• Total bilirubin ≤ 1.5 X ULN (unless there is lymphoma in the liver)

• Age ≥18 years

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

Exclusion Criteria:

• Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.

• Patients currently receiving anticancer therapies or who have received anticancer therapies within 30 days of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.). Steroids for symptom palliation are allowed, but must be either discontinued or on stable doses at the time of initiation of protocol therapy.

• Patients may not be receiving any other investigational agents, or have received investigational agents within 4 weeks of beginning treatment.

• Patients who have previously received PGG-Betafectin (Betafectin®) or Imprime PGG.

• Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study.

• Patients with known leptomeningeal or brain metastases. Imaging or spinal fluid analysis to exclude CNS involvement is not required, unless there is clinical suspicion by the treating investigator.

• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy or a known hypersensitivity to baker's yeast.

• Patients with known HIV infection or hepatitis B or C infection.HIV testing is not mandated and is to be performed at the discretion of the treating investigator.

• Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).

• Prior history of another malignancy (except for non-melanoma skin cancer or in situ cervical or breast cancer) unless disease free for at least three years. Patients with prostate cancer are allowed if PSA is less than 1.

• Patients should not receive immunization with attenuated live vaccine within one week of study entry or during study period.

• Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. Women of child bearing potential (WOCBP) or male study participants of reproductive potential must agree to use double barrier birth control method of contraception during the course of the study treatment period and for 3 months after completing study treatment.

-- WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who are not postmenopausal (no menses) for at least 12 consecutive months. WOCBP must have a negative urine or serum pregnancy test within 7 days prior to administration of treatment.

• History of noncompliance to medical regimens.

• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:

• New York Heart Association Class III or IV cardiac disease, including pre-existing clinically significant arrhythmia, congestive heart failure, or cardiomyopathy

• unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease

• Other uncontrolled intercurrent illness that would limit adherence to study requirements.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Dana-Farber Cancer Institute
• HiberCell, Inc.

Investigators

• Principal Investigator: Caron Jacobson, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 13, 2018

More Information

Publications

None provided.

• Responsible Party: Caron A. Jacobson, Principal Investigator, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT02086175
• Other Study ID Numbers: 13-398
• First Posted: Mar 13, 2014
• Last Update Posted: Apr 5, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Caron A. Jacobson, Principal Investigator, Dana-Farber Cancer Institute: relapsed/refractory indolent B cell non-Hodgkin lymphomas
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Rituximab

Study Results

Participant Flow

Arm/Group Title	Imprime PGG and Rituximab
Arm/Group Description	The study drug, Imprime PGG, will be administered intravenously at a dose of 4mg/kg weekly for 4 weeks. Rituximab will be administered intravenously by institutional standards concurrently at a dose of 375mg/m2 weekly for 4 weeks. Response will be assessed with CT scans 10 weeks +/- 3 days following the completion of treatment Imprime PGG Rituximab
Period Title: Overall Study
STARTED	25
COMPLETED	25
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Imprime PGG and Rituximab
Arm/Group Description	The study drug, Imprime PGG, will be administered intravenously at a dose of 4mg/kg weekly for 4 weeks. Rituximab will be administered intravenously by institutional standards concurrently at a dose of 375mg/m2 weekly for 4 weeks. Response will be assessed with CT scans 10 weeks +/- 3 days following the completion of treatment Imprime PGG Rituximab
Overall Participants	25
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	13 52%
>=65 years	12 48%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63
Sex: Female, Male (Count of Participants)
Female	13 52%
Male	12 48%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	24 96%
Unknown or Not Reported	1 4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	25 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	25 100%
ECOG Performance Status (Count of Participants)
0 - Fully Active	18 72%
1 - Restricted	7 28%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate
Description	Overall response rate is percentage of participants with complete (CR) and partial (PR) responses as best response during treatment. CR: Nodal Masses: For FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative For variably FDG-avid or PET negative; regression to normal size on CT. Liver/Spleen: No palpable nodules -Bone Marrow Infiltrate cleared on repeat biopsy; if indeterminate by morphology, immunohistochemistry should be negative. PR: Nodal Masses: 50% decrease in SPD of up to 6 largest dominant masses; no increase in size of other nodes. FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site. Variably FDG-avid or PET negative; regression on CT. Liver/Spleen: 50% decrease in SPD of nodules; no increase in size of liver or spleen. Bone Marrow: Irrelevant if positive prior to therapy; cell type should be specified.
Time Frame	Response assessed at week 14 of study calendar (10 weeks after the 4-week treatment regimen).

Outcome Measure Data

Analysis Population Description

All evaluated participants including two (2) non evaluable (NE) participants with partial or complete response (PR, CR)

Arm/Group Title	Imprime PGG and Rituximab
Arm/Group Description	The study drug, Imprime PGG, will be administered intravenously at a dose of 4mg/kg weekly for 4 weeks. Rituximab will be administered intravenously by institutional standards concurrently at a dose of 375mg/m2 weekly for 4 weeks. Response will be assessed with CT scans 10 weeks +/- 3 days following the completion of treatment Imprime PGG Rituximab
Measure Participants	25
Count of Participants [Participants]	12 48%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Imprime PGG and Rituximab
	Comments	Patients will be accrued in a single stage design, with a goal accrual of 25 patients. Assuming a 30% response rate with rituximab alone, if the true but unknown rate of CR or PR is 50% with the addition of Imprime PGG, the probability of observing 11 or more patients with a response is 0.79 with 0.098 one-sided type-I error. Therefore a study with 25 patients, in which an observed response rate of 11/25 (44%) would be considered worthy of further consideration.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.044
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	percent
	Estimated Value	48
	Confidence Interval	(2-Sided) 90%; 31 to 66
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Median Progression-free Survival (PFS)
Description	Progression free survival (PFS) is defined as the time from start of treatment to disease progression or death from any cause as estimated by Kaplan Meier methods. Patients who have not progressed and are alive are censored at the date the patient is known to be progression-free. Response is measure using the International Harmonization Project for Lymphoma criteria Cheson 2007, using CT scans of the chest, abdomen, and pelvis.
Time Frame	Patients were followed for a median (range) of 13.6 months (3-25).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Imprime PGG and Rituximab
Arm/Group Description	The study drug, Imprime PGG, will be administered intravenously at a dose of 4mg/kg weekly for 4 weeks. Rituximab will be administered intravenously by institutional standards concurrently at a dose of 375mg/m2 weekly for 4 weeks. Response will be assessed with CT scans 10 weeks +/- 3 days following the completion of treatment Imprime PGG Rituximab
Measure Participants	25
Median (Full Range) [months]	14.4

3. Secondary Outcome

Title	Duration of Response (DOR)
Description	Duration of response DR is defined as the time from the date of first response (complete or partial) after treatment to the date of disease progression or death for any cause. Patients who are alive without progression are censored at the date the patient is last know to be progression-free.
Time Frame	Patients were followed for a median (range) of 13.6 months (3-25).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Imprime PGG and Rituximab
Arm/Group Description	The study drug, Imprime PGG, will be administered intravenously at a dose of 4mg/kg weekly for 4 weeks. Rituximab will be administered intravenously by institutional standards concurrently at a dose of 375mg/m2 weekly for 4 weeks. Response will be assessed with CT scans 10 weeks +/- 3 days following the completion of treatment Imprime PGG Rituximab
Measure Participants	25
Median (Full Range) [months]	11.8

4. Secondary Outcome

Title	Imprime PGG-bound Neutrophils Status by Response
Description	Imprime PGG-bound neutrophils analyzed using established methods (peripheral blood samples and post-treatment tumor samples to quantify the binding of Imprime PGG to neutrophils) by treatment response, best response.
Time Frame	Up to 14 weeks with a median (range of) 13 weeks (12-14).

Outcome Measure Data

Analysis Population Description

Imprime PGG-bound neutrophil status only available for this analysis population.

Arm/Group Title	Imprime PGG and Rituximab
Arm/Group Description	The study drug, Imprime PGG, will be administered intravenously at a dose of 4mg/kg weekly for 4 weeks. Rituximab will be administered intravenously by institutional standards concurrently at a dose of 375mg/m2 weekly for 4 weeks. Response will be assessed with CT scans 10 weeks +/- 3 days following the completion of treatment Imprime PGG Rituximab
Measure Participants	22
Complete Response	0 0%
Partial Response	4 16%
Stable Disease	4 16%
Progressive Disease	0 0%
Complete Response	1 4%
Partial Response	5 20%
Stable Disease	4 16%
Progressive Disease	4 16%

Adverse Events

Time Frame	Up to 66 weeks
Arm/Group Title	Imprime PGG and Rituximab
Arm/Group Description	The study drug, Imprime PGG, will be administered intravenously at a dose of 4mg/kg weekly for 4 weeks. Rituximab will be administered intravenously by institutional standards concurrently at a dose of 375mg/m2 weekly for 4 weeks. Response will be assessed with CT scans 10 weeks +/- 3 days following the completion of treatment Imprime PGG Rituximab
All Cause Mortality
	Imprime PGG and Rituximab
	Affected / at Risk (%)	# Events
Total	2/25 (8%)
Serious Adverse Events
	Imprime PGG and Rituximab
	Affected / at Risk (%)	# Events
Total	0/25 (0%)
Other (Not Including Serious) Adverse Events
	Imprime PGG and Rituximab
	Affected / at Risk (%)	# Events
Total	12/25 (48%)
Gastrointestinal disorders
Diarrhea	1/25 (4%)	1
Dry mouth	1/25 (4%)	1
General disorders
Infusion related reaction	5/25 (20%)	8
Fatigue	2/25 (8%)	2
Chills	1/25 (4%)	1
Infections and infestations
Otitis externa	1/25 (4%)	1
Investigations
Alanine aminotransferase increased	1/25 (4%)	1
Alkaline phosphatase increased	1/25 (4%)	1
Aspartate aminotransferase increased	1/25 (4%)	1
Neutrophil count decreased	1/25 (4%)	2
White blood cell decreased	1/25 (4%)	2
Metabolism and nutrition disorders
Hyponatremia	1/25 (4%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	2/25 (8%)	3
Musculoskeletal and connective tissue disorder - Other, specify	1/25 (4%)	1
Nervous system disorders
Peripheral sensory neuropathy	1/25 (4%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/25 (4%)	1
Dyspnea	1/25 (4%)	1

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.