Phase 2 N=30 Randomized Treatment

Open Label Multicenter Study of CVP Followed by Iodine-131 Anti-B1 Antibody for Subjects With Untreated Low-Grade Non Hodgkin's Lymphoma.

Lymphoma, Non-Hodgkin

Bottom Line

View on ClinicalTrials.gov: NCT01663714 ↗

Enrolled (actual)

Serious AEs

31.1%

Results posted

Apr 2013

Primary outcome: Primary: Number of Participants (Par.) With Unconfirmed Response (Complete Response, Complete Response/Unconfirmed, or Partial Response), as Assessed by the Investigator — 30 participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: cycolophosphamide, vacristine, and pednisone (CVP) x6 cycles followed by tositumomab and iodine I 131 tositumomab. (Biological)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: GlaxoSmithKline
Primary completion: Feb 2012

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants (Par.) With Unconfirmed Response (Complete Response, Complete Response/Unconfirmed, or Partial Response), as Assessed by the Investigator	30	—
PRIMARY Number of Participants (Par.) With Confirmed Response (Complete Response [CR], Complete Response/Unconfirmed [CRu], or Partial Response [PR]), as Assessed by the Investigator	30	—
SECONDARY Number of Participants With Unconfirmed Complete Response (CR), as Assessed by the Investigator	21	—
SECONDARY Number of Participants With Confirmed Complete Response (CR), as Assessed by the Investigator	21	—
SECONDARY Duration of Response (DOR), as Assessed by the Investigator	129.6; 129.6	—
SECONDARY DOR for Unconfirmed and Confirmed Complete Response, as Assessed by the Investigator	129.6; 129.6	—
SECONDARY Time to Progression of Disease or Death, as Assessed by the Investigator	110.2	—
SECONDARY Time to Treatment Failure, as Assessed by the Investigator	78.9	—
SECONDARY Total Body Residence Time (TBRT; Average Amount of Time TST Spends in the Body, Calculated From the Rate of TB Clearance of Radioactivity During the Dosimetric Dose [DD]) of Iodine 131 TST Antibody Following the DD	103.7	—
SECONDARY Time to Nadir for Hematological Parameters: Absolute Neutrophil Count (ANC), Hemoglobin, Platelets, and White Blood Cell (WBC) Count	49.0; 49.0; 35.5; 44.0	—
SECONDARY Time to Recovery (TTR) to Baseline (BL) for Hematologic Laboratory (Lab.) Evaluations	77.0; 76.5; 60.5; 126.5	—
SECONDARY Nadir Values for Absolute Neutrophil Count (ANC)	0.4	—
SECONDARY Nadir Values for Hemoglobin	10.6	—
SECONDARY Nadir Values for Platelet Count	57.0	—
SECONDARY Nadir Values for WBC Count	1.8	—
SECONDARY Number of Participants With the Indicated Grade 3 or Grade 4 Adverse Events (AEs)	29; 23; 12; 2; 15; 6	—
SECONDARY Number of Participants With the Indicated Grade 3 or Grade 4 AEs Possibly or Probably Related to Study Drug	29; 23; 12; 2; 15; 6	—
SECONDARY Number of Participants With Any Treatment-related Serious Adverse Event (SAE)	5; 2; 2; 2; 1; 1	—
SECONDARY Number of Participants With the Indicated Primary Cause of Death	5; 1; 3	—
SECONDARY Number of Participants Who Received Any Supportive Care	17	—
SECONDARY Number of Participants Who Were Negative for Human Anti-murine Antibodies (HAMA) at Baseline (Study Entry) But Positive or Negative at Month 24	0; 30	—
SECONDARY Overall Survival	NA	—

Summary

This is a phase II, open-label, multicenter study of the efficacy and safety of sequential administration of CVP x 6 followed by tositumomab and iodine I 131 tositumomab (formerly referred to as tositumomab and iodine I 131 tositumomab). All patients who complete three cycles of CVP, regardless of response, will be eligible for treatment with tositumomab and iodine I 131 tositumomab. Subjects who have rapidly progressive disease prior to completing three cycles of CVP may be removed from study. In order to proceed to tositumomab and iodine I 131 tositumomab therapy, patients must have completed six cycles of CVP within 20 weeks as described. Patients may proceed to Iodine-131 Anti-B1 Antibody if they have progressive disease documented at the response evaluation following 6 cycles of CVP. In addition, patients must still meet the eligibility inclusion exclusion criteria based upon the week 20 assessments, as applicable. Patients must also have an average of ≤25% bone marrow involved by NHL to receive treatment with tositumomab and iodine I 131 tositumomab. The dosimetric dose of tositumomab and iodine I 131 tositumomab must be given within 28 days of the response evaluation following CVP and no later than 56 days from the first day of the sixth cycle of CVP.

Eligibility Criteria

Inclusion Criteria

Subjects must have a histologically confirmed initial diagnosis of low-grade non-Hodgkin's B-cell lymphoma according to the International Working Formulation (IWF) (32) (i.e., small lymphocytic with or without plasmacytoid differentiation; follicular small cleaved cell; or follicular, mixed small cleaved and large cell).
Subjects must have Ann Arbor Stage III, Stage IV, or bulky Stage II disease at diagnosis. Bulky Stage II is defined as a mediastinal mass greater than one-third of the maximum chest diameter, or any other mass greater than or equal to 10 cm in maximum diameter.
Subjects must have evidence that their tumor tissue expresses the CD20 antigen. Immunoperoxidase stains of paraffin-embedded tissue showing positive reactivity with L26 antibody or immunoperoxidase stains of frozen tissue showing positive reactivity with Anti B1 Antibody (Coulter Clone®) or similar commercially available CD20 antibody or evidence of CD20 positivity by flow cytometry are acceptable evidence of CD20 positivity. Testing of tumor tissue from any time in the course of the patient's disease is acceptable.
Subjects must have a performance status of at least 60% on the Karnofsky Performance Scale and an anticipated survival of at least 3 months.
Subjects must have an ANC≥1500 cells/mm3 and a platelet count ≥100,000 cells/mm3 within 14 days of study enrollment. These blood counts must be sustained without support of hematopoietic cytokines or transfusion of blood products.
Subjects must have adequate renal function (defined as serum creatinine <1.5 times the upper limit of normal) and hepatic function (defined as total bilirubin <1.5 times the upper limit of normal and AST <5 times the upper limit of normal) within 14 days of study enrollment.
Subjects must have bi-dimensionally measurable disease. At least one lesion must be ≥2.0x2.0 cm by computerized tomography scan.
Subjects must be at least 18 years of age.
Subjects of childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.
Subjects must give written informed consent and sign an IRB-approved informed consent form prior to study enrollment.

Exclusion Criteria

Subjects who have received prior chemotherapy, biologic therapy, steroids, or radiation therapy as treatment for their NHL.
Subjects with active obstructive hydronephrosis.
Subjects with New York Heart Association class III or IV heart disease or other serious illness that would preclude evaluation.
Subjects with prior malignancy other than lymphoma, except for adequately treated skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for 5 years. Patients who have been disease-free of another cancer for greater than 5 years must be carefully assessed at the time of study entry to rule out recurrent disease.
Subjects with known HIV infection.
Subjects who are HAMA positive.
Subjects with known brain or leptomeningeal metastases.
Subjects who are pregnant or breastfeeding. Males and females must agree to use a contraceptive method from enrollment to 6 months after receiving Iodine 131 Anti B1 Antibody.
Subjects with active infection requiring IV anti-infectives at the time of study enrollment.
Subjects with intermediate- or high-grade NHL.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01663714). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.