Hematopoietic Stem Cell Transplant for Recurrent Non-Hodgkin's Lymphoma

NCT00574509 | Completed Phase 1 FDA Drug FDA Device

• 1 other identifier: 0165-96-FB
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the safety of 131I-anti-B1 Radioimmunotherapy when combined with high-dose BEAM or BEAC chemotherapy and hematopoietic stem cell transplantation. The study will also compare the difference in response rates and time to treatment failure between historical control patients receiving high-dose BEAM or BEAC chemotherapy with autologous hematopoietic stem cell transplant and patients receiving radioimmunotherapy and high-dose BEAM or BEAC chemotherapy with autologous hematopoietic stem cell transplant. Patients will receive escalating doses of radioimmunotherapy with anti-B1 radiolabeled with 131Iodine, high-dose carmustine, etoposide, cytarabine and Melphalan (BEAM) chemotherapy, and autologous hematopoietic stem cell transplant.

Conditions

Lymphoma

Keywords

NHL; Non Hodgkins Lymphoma; 131Iodine-Anti-B1 Radioimmunotherapy; Autologous Hematopoietic Stem Cell Transplant; AHSCT

Outcome Measures

Primary Outcomes (1)

• Safety of 131I-anti-B1 radioimmunotherapy when combined with high-dose BEAM or BEAC chemotherapy & HSCT

  Safety of 131I-anti-B1 radioimmunotherapy when combined with high-dose BEAM or BEAC chemotherapy \& HSCT. Calculations will be made such that in a dose escation study, whole body radiation doses of 30, 45, 60, and 75cGy will result from the administration of the therapeutic activity of 131I-anti-B1.

  During treatment

Secondary Outcomes (1)

• Comparing high-dose BEAM or BEAC chemo. with autologous HSCT and radioimmunotherapy and high-dose BEAM or BEAC chemo. with autologous HSCT

  time of registration to time of treatment discontinuation

Study Arms (1)

131I-Anti-B1

EXPERIMENTAL

BEAM + 131Iodine-Anti-B1 radioimmunotherapy and autologous HSCT

Radiation: 131Iodine-Anti-B1 Radioimmunotherapy; Drug: BEAM

Interventions

131Iodine-Anti-B1 Radioimmunotherapy RADIATION

Dosimetric dose of 450 mg unlabeled Anti-B1 followed by 35 mg Anti-B1 which has been trace labeled with 5mCi of 131I-Anti-B1.

131I-Anti-B1

BEAM DRUG

Carmustine (B) also known as BCNU Etoposide (E) Cytarabine (A) also known as Ara-C and cytosine arabinoside Melphalan (M) also known as alkeran

Also known as: Carmustine, Etoposide, Cytarabine, and Melphalan

131I-Anti-B1

Eligibility Criteria

• Age: 19 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pts with a diagnosis of indolent or aggressive B-cell non-Hodgkin's lymphoma who have failed \> 3 prior therapies, or are chemo resistant or refractory. Patients must be otherwise eligible for high-dose therapy with the BEAM protocol and ABMT or PSCT.
• Pts without evidence of severe organ dysfunction.
• The pre-transplant bone marrow biopsy must show no evidence of marrow involvement if an autologous BMT is to be performed and adequate cellularity, alternatively autologous PSCT will be considered if the bone marrow involvement is \<25%.
• The pt must have no other major medical problems and specifically life expectancy must be at least 4 months post transplant, with a performance status Karnofsky score of \>70.
• Pts with evidence that their tumor tissue expresses the CD20 antigen. Immunoperoxidase stains of tissue showing positive reactivity with L26 antibody or flow cytometry studies are acceptable evidence of CD20 positivity. Testing of tumor tissue from any time in the course of the patient's disease is acceptable.
• Pts must have normal renal function (creatinine \< 2.0 mg/dL) and hepatic function (bilirubin \< 2.0 mg/dL) within seven days of study entry.
• Pts with DLCO \>50% of predicted.
• If pt is \>60 years or has a significant cardiac history (MI or CHF) or has received \>350 mg/m2 of Adriamycin and ejection fraction must be \>40%.
• Pts must give written informed consent and sign an approved informed consent form prior to study entry.
• ts must have bidimensionally measurable disease.
• Females of child-bearing potential must have a negative serum pregnancy test prior to enrollment to the study, followed by the use of an effective method of birth control.

You may not qualify if:

• Pts with more than 25% of the intratrabecular marrow space involved by lymphoma in a unilateral bone marrow biopsy specimens as assessed microscopically prior to study entry.
• Pts who have received cytotoxic chemotherapy, radiation therapy or immunosuppressants within THREE weeks prior to the radioimmunoconjugate dose or who exhibit persistent clinical evidence of toxicity. The use of steroids must have been discontinued (except maintenance-dose steroids).
• Pts with obstructive hydronephrosis.
• Pts with evidence of active infection requiring intravenous antibiotics at the time of study entry.
• Pts with New York Heart Association class 3 or 4 heart disease or other serious illness that would preclude evaluation.
• Pts with prior malignancy other than lymphoma, except for adequately treated skin ca, in situ cervical ca, or other ca for which patient has been disease-free for 5 years.
• Pts with known HIV infection.
• Pts with known brain or leptomeningeal metastases.
• Pts who are pregnant. Patients of child-bearing potential must undergo a pregnancy test. Males and females must agree to use effective contraception during the study and females must continue effective contraception for one year following the radioimmunotherapy dose.
• Pts with previous allergic reactions to iodine. This does not include IV contrast materials.
• Pts who previously received radioimmunotherapy.
• Pts with progressive disease in a field that has been previously irradiated with more than 3500 cGy within the past year.
• Pts who are on another protocol involving non-FDA approved drugs or biologics.
• No vulnerable subjects will be entered into this study.
• Pts with a positive HAMA test at baseline will not be entered. Patients with a positive HAMA test at the end of the week following dosimetric dose administration may not continue on to receive the radioimmunotherapy dose without first contacting the FDA.

Sponsors & Collaborators

• University of Nebraska: lead

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198-7680, United States

Location

MeSH Terms

Conditions

Lymphoma; Lymphoma, Non-Hodgkin

Interventions

Carmustine; Etoposide; Cytarabine; Melphalan

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Julie M Vose, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2007
• First Posted: December 17, 2007
• Study Start: March 4, 1996
• Primary Completion: November 1, 2014
• Study Completion: December 10, 2014
• Last Updated: October 10, 2023

Record last verified: 2023-10

Locations

US (1)