Trial Outcomes & Findings for Trial of Low-Dose Methotrexate and I 131 Tositumomab for Previously Untreated, Advanced-Stage, Follicular Lymphoma (NCT NCT01389076)

Last Updated: 2017-01-30

Results Overview

The percentage of patients that experience early onset HAMA conversion following treatment. Early-onset HAMA is defined as antimouse antibody levels (in blood serum) of at least 5 times the level of detection, occurring at or prior to the 7th week of I-131 tositumomab therapy.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

22 participants

Primary outcome timeframe

7 weeks

Results posted on

2017-01-30

Participant Flow

Participant milestones

Participant milestones
Measure	Methotrexate and Bexxar Low dose methotrexate and Bexxar (tositumomab) Patients will begin taking methotrexate 7.5 mg orally once weekly 3 weeks prior to initiating I-131 tositumomab, with additional weekly doses once I-131 tositumomab therapy has begun for a total of 10 doses. On Study Day 0, patients will receive the IV administration of 450 mg unlabeled tositumomab followed by the IV administration of the dosimetric dose (5 mCi of Iodine I 131 tositumomab).
Overall Study STARTED	22
Overall Study COMPLETED	22
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Trial of Low-Dose Methotrexate and I 131 Tositumomab for Previously Untreated, Advanced-Stage, Follicular Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Methotrexate and Bexxar n=22 Participants Low dose methotrexate and Bexxar (tositumomab) Patients will begin taking methotrexate 7.5 mg orally once weekly 3 weeks prior to initiating I-131 tositumomab, with additional weekly doses once I-131 tositumomab therapy has begun for a total of 10 doses. On Study Day 0, patients will receive the IV administration of 450 mg unlabeled tositumomab followed by the IV administration of the dosimetric dose (5 mCi of Iodine I 131 tositumomab).
Age, Continuous	56 years n=5 Participants
Gender Female	9 Participants n=5 Participants
Gender Male	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: 7 weeks

Outcome measures

Outcome measures
Measure	Methotrexate and Bexxar n=22 Participants Low dose methotrexate and Bexxar (tositumomab) Patients will begin taking methotrexate 7.5 mg orally once weekly 3 weeks prior to initiating I-131 tositumomab, with additional weekly doses once I-131 tositumomab therapy has begun for a total of 10 doses. On Study Day 0, patients will receive the IV administration of 450 mg unlabeled tositumomab followed by the IV administration of the dosimetric dose (5 mCi of Iodine I 131 tositumomab).
Rate of Early Onset HAMA (Human Anti-mouse Antibody) Conversion Following Treatment	18.2 percentage of participants Interval 5.2 to 40.3

SECONDARY outcome

Timeframe: 2 years

The overall response rate (PR \[partial response\] + CR \[complete response\]) was determined. Partial response is defined as the regression of measurable disease with no new sites of disease. Complete response is defined as the disappearance of all evidence of disease.

Outcome measures

Outcome measures
Measure	Methotrexate and Bexxar n=22 Participants Low dose methotrexate and Bexxar (tositumomab) Patients will begin taking methotrexate 7.5 mg orally once weekly 3 weeks prior to initiating I-131 tositumomab, with additional weekly doses once I-131 tositumomab therapy has begun for a total of 10 doses. On Study Day 0, patients will receive the IV administration of 450 mg unlabeled tositumomab followed by the IV administration of the dosimetric dose (5 mCi of Iodine I 131 tositumomab).
Percentage of Participants That Respond to Treatment	90.9 percentage of participants Interval 70.8 to 98.9

SECONDARY outcome

Timeframe: 2 years

Overall survival was examined at 2 years

Outcome measures

Outcome measures
Measure	Methotrexate and Bexxar n=22 Participants Low dose methotrexate and Bexxar (tositumomab) Patients will begin taking methotrexate 7.5 mg orally once weekly 3 weeks prior to initiating I-131 tositumomab, with additional weekly doses once I-131 tositumomab therapy has begun for a total of 10 doses. On Study Day 0, patients will receive the IV administration of 450 mg unlabeled tositumomab followed by the IV administration of the dosimetric dose (5 mCi of Iodine I 131 tositumomab).
The Percentage of Participants Alive at 2 Years	100 percentage of participants

SECONDARY outcome

Timeframe: 2 Years

Population: Due to the withdrawal of Bexxar by the manufacture and failure to find another supplier, the trial was abandoned and follow-up scans were not obtained. Therefore only survival is known. Progression information is not available.

The median time patients survived without progression.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to week 13

Outcome measures

Outcome measures
Measure	Methotrexate and Bexxar n=22 Participants Low dose methotrexate and Bexxar (tositumomab) Patients will begin taking methotrexate 7.5 mg orally once weekly 3 weeks prior to initiating I-131 tositumomab, with additional weekly doses once I-131 tositumomab therapy has begun for a total of 10 doses. On Study Day 0, patients will receive the IV administration of 450 mg unlabeled tositumomab followed by the IV administration of the dosimetric dose (5 mCi of Iodine I 131 tositumomab).
Number of Participants That Experienced SAEs During Treatment.	2 participants

Adverse Events

Methotrexate and Bexxar

Serious events: 4 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Methotrexate and Bexxar n=22 participants at risk Low dose methotrexate and Bexxar (tositumomab) Patients will begin taking methotrexate 7.5 mg orally once weekly 3 weeks prior to initiating I-131 tositumomab, with additional weekly doses once I-131 tositumomab therapy has begun for a total of 10 doses. On Study Day 0, patients will receive the IV administration of 450 mg unlabeled tositumomab followed by the IV administration of the dosimetric dose (5 mCi of Iodine I 131 tositumomab).
Musculoskeletal and connective tissue disorders back pain	4.5% 1/22
Musculoskeletal and connective tissue disorders bilateral Arm Pain	4.5% 1/22
General disorders pain	4.5% 1/22
General disorders pain due to disease progression	4.5% 1/22
Gastrointestinal disorders rectal fissures	4.5% 1/22

Other adverse events

Other adverse events
Measure	Methotrexate and Bexxar n=22 participants at risk Low dose methotrexate and Bexxar (tositumomab) Patients will begin taking methotrexate 7.5 mg orally once weekly 3 weeks prior to initiating I-131 tositumomab, with additional weekly doses once I-131 tositumomab therapy has begun for a total of 10 doses. On Study Day 0, patients will receive the IV administration of 450 mg unlabeled tositumomab followed by the IV administration of the dosimetric dose (5 mCi of Iodine I 131 tositumomab).
Gastrointestinal disorders abdominal pain	22.7% 5/22
General disorders achiness - whole body	4.5% 1/22
Skin and subcutaneous tissue disorders acne	4.5% 1/22
Blood and lymphatic system disorders Anemia	4.5% 1/22
Metabolism and nutrition disorders Anorexia	4.5% 1/22
Psychiatric disorders Anxiety	4.5% 1/22
Musculoskeletal and connective tissue disorders Arterosclerosis calcifications on spine	4.5% 1/22
Musculoskeletal and connective tissue disorders back pain	9.1% 2/22
Nervous system disorders bad smell	4.5% 1/22
Nervous system disorders Bilateral Arm Paresthesias	4.5% 1/22
Vascular disorders Bilateral Foot Swelling	4.5% 1/22
Musculoskeletal and connective tissue disorders Bilateral Leg Pain	4.5% 1/22
Gastrointestinal disorders bleeding gums	9.1% 2/22
Gastrointestinal disorders Bloating	4.5% 1/22
Gastrointestinal disorders Blood in stool	4.5% 1/22
Vascular disorders bruising	13.6% 3/22
Nervous system disorders Burning sensation of skin	4.5% 1/22
Musculoskeletal and connective tissue disorders Chest Tenderness	4.5% 1/22
General disorders Chills	13.6% 3/22
Gastrointestinal disorders Cholelithiasis	4.5% 1/22
Eye disorders conjunctivitis	4.5% 1/22
Gastrointestinal disorders Constipation	18.2% 4/22
Blood and lymphatic system disorders Decreased ANC	27.3% 6/22
Blood and lymphatic system disorders Decreased WBC	27.3% 6/22
Metabolism and nutrition disorders Dehydration	4.5% 1/22
Gastrointestinal disorders Diarrhea	22.7% 5/22
Nervous system disorders Dizziness	4.5% 1/22
Skin and subcutaneous tissue disorders Dry Skin	4.5% 1/22
Gastrointestinal disorders dysgeusia	4.5% 1/22
Respiratory, thoracic and mediastinal disorders dyspnea	4.5% 1/22
Investigations Elevated Creatinine	4.5% 1/22
Skin and subcutaneous tissue disorders Facial Flushing	4.5% 1/22
General disorders Fatigue	36.4% 8/22
General disorders Fever	9.1% 2/22
Injury, poisoning and procedural complications Finger Puncture wound	4.5% 1/22
General disorders flu-like symptoms	4.5% 1/22
Psychiatric disorders forgetful	4.5% 1/22
Musculoskeletal and connective tissue disorders General Arthalgias	4.5% 1/22
Musculoskeletal and connective tissue disorders General Myalgias	4.5% 1/22
Skin and subcutaneous tissue disorders Generalized Itching	4.5% 1/22
Skin and subcutaneous tissue disorders Generalized rash	4.5% 1/22
Nervous system disorders Hand Paresthesia	4.5% 1/22
Nervous system disorders Hand tremor	4.5% 1/22
Nervous system disorders Headache	27.3% 6/22
Skin and subcutaneous tissue disorders hyperpigmentation	4.5% 1/22
Investigations Hypothyroidism	9.1% 2/22
Immune system disorders infusion related reaction	4.5% 1/22
Psychiatric disorders Insomnia	4.5% 1/22
Psychiatric disorders irritable	4.5% 1/22
Skin and subcutaneous tissue disorders Itching	13.6% 3/22
Musculoskeletal and connective tissue disorders Jaw pain	4.5% 1/22
Musculoskeletal and connective tissue disorders Left hip pain	4.5% 1/22
Musculoskeletal and connective tissue disorders Leg pain - bilateral	4.5% 1/22
Gastrointestinal disorders loose stool	4.5% 1/22
Nervous system disorders Lower extremity neuropathy	4.5% 1/22
Vascular disorders Lower extremity swelling	4.5% 1/22
Blood and lymphatic system disorders Lymphocyte count decreased	4.5% 1/22
Musculoskeletal and connective tissue disorders Mild Narrowing of C3-4, C4-5	4.5% 1/22
Musculoskeletal and connective tissue disorders Muscle Soreness	4.5% 1/22
Respiratory, thoracic and mediastinal disorders Nasal polyps	4.5% 1/22
Gastrointestinal disorders Nausea	50.0% 11/22
General disorders Night sweats	4.5% 1/22
Respiratory, thoracic and mediastinal disorders Non-productive cough	9.1% 2/22
Nervous system disorders numbness hands	4.5% 1/22
Respiratory, thoracic and mediastinal disorders occasional Wheezing	4.5% 1/22
General disorders Pain around tumor site	4.5% 1/22
Musculoskeletal and connective tissue disorders Pain in bilateral axilla	4.5% 1/22
Musculoskeletal and connective tissue disorders Pain in extremity	4.5% 1/22
Musculoskeletal and connective tissue disorders Pain in lower extremities and bilateral groin	4.5% 1/22
Musculoskeletal and connective tissue disorders Pain on bilateral feet	4.5% 1/22
Skin and subcutaneous tissue disorders Papular rash on anterior chest	4.5% 1/22
Skin and subcutaneous tissue disorders Papular rash on lower neck	4.5% 1/22
Eye disorders Periorbital edema	4.5% 1/22
Psychiatric disorders Phonophobia	4.5% 1/22
Eye disorders Photophobia	4.5% 1/22
Skin and subcutaneous tissue disorders Pityriasis Rosea	4.5% 1/22
Musculoskeletal and connective tissue disorders pleuritic chest pain	4.5% 1/22
Respiratory, thoracic and mediastinal disorders Productive cough	4.5% 1/22
Respiratory, thoracic and mediastinal disorders Pulmonary nodules	4.5% 1/22
Skin and subcutaneous tissue disorders Puritus	4.5% 1/22
Skin and subcutaneous tissue disorders Rash on tumor site	4.5% 1/22
Skin and subcutaneous tissue disorders rash, neck	4.5% 1/22
Gastrointestinal disorders Rectal bleeding	4.5% 1/22
Respiratory, thoracic and mediastinal disorders Rhinnorhea	4.5% 1/22
Injury, poisoning and procedural complications Right ankle fracture	4.5% 1/22
Musculoskeletal and connective tissue disorders Right leg Pain	4.5% 1/22
Nervous system disorders Right Leg Paresthesia	4.5% 1/22
Respiratory, thoracic and mediastinal disorders Right maxillary sinus pain	4.5% 1/22
Skin and subcutaneous tissue disorders Scaly rash on upper extremities, bilateral	4.5% 1/22
Musculoskeletal and connective tissue disorders Shoulder pain	4.5% 1/22
Respiratory, thoracic and mediastinal disorders Sinus congestion	13.6% 3/22
Infections and infestations Sinus infection	9.1% 2/22
Respiratory, thoracic and mediastinal disorders sinus pressure	4.5% 1/22
Vascular disorders Small scattered ecchymosis on lower extremities	4.5% 1/22
Gastrointestinal disorders Sore Throat	13.6% 3/22
Eye disorders Swelling around eyes	4.5% 1/22
Blood and lymphatic system disorders thrombocytopenia	27.3% 6/22
Infections and infestations upper respiratory infection	13.6% 3/22
Renal and urinary disorders Urinary Frequency	4.5% 1/22
Renal and urinary disorders UTI	4.5% 1/22
Gastrointestinal disorders Vomiting	13.6% 3/22
Nervous system disorders warm/burning sensation in throat	4.5% 1/22
Nervous system disorders wooziness	4.5% 1/22
Gastrointestinal disorders Worsening GERD	4.5% 1/22
Reproductive system and breast disorders yeast infection	4.5% 1/22

Additional Information

Dr. Mark Kaminski, M.D.

University of Michigan Comprehensive Cancer Center

Phone: 734-936-5310

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place