A Phase I Study of 90Y-DOTA-Peptide-Lym-1 With Peripheral Blood Stem Cell Support, Paclitaxel And Cyclosporin A In Patients With Non-Hodgkin's Lymphoma
Monoclonal Antibody Therapy, Chemotherapy, and Peripheral Stem Cell Transplantation in Treating Patients With Refractory Non-Hodgkin's Lymphoma
Sponsors
Source
National Cancer Institute (NCI)
Brief Summary
RATIONALE: Monoclonal antibodies can locate cancer cells and either kill them or deliver
tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use
different ways to stop cancer cells from dividing so they stop growing or die. Peripheral
stem cell transplantation may allow doctors to give higher doses of chemotherapy and kill
more cancer cells.
PURPOSE: Phase I trial to study the effectiveness of monoclonal antibody therapy,
cyclosporine, and paclitaxel followed by peripheral stem cell transplantation in treating
patients who have refractory non-Hodgkin's lymphoma.
Detailed Description
OBJECTIVES:
- Determine the maximum tolerated dose of yttrium Y 90 monoclonal antibody Lym-1
administered with cyclosporine and paclitaxel followed by autologous peripheral blood
stem cell transplantation in patients with refractory non-Hodgkin's lymphoma.
- Determine the toxicity of this treatment regimen in these patients.
OUTLINE: This is an open-label, dose escalation study of yttrium Y 90 monoclonal antibody
Lym-1 (Y90 MOAB Lym-1). Patients are assigned to one of four cohorts.
- Cohort I: Patients receive filgrastim (G-CSF) subcutaneously (SC) beginning 4 days prior
to peripheral blood stem cell (PBSC) mobilization and continuing until adequate PBSC are
collected. Patients receive unlabeled monoclonal antibody (MOAB) Lym-1 IV followed by a
tracer dose of indium In 111 MOAB Lym-1 (In111 MOAB Lym-1) IV on day 0 and unlabeled
MOAB Lym-1 IV followed by Y90 MOAB Lym-1 IV on day 7. Patients also receive oral
cyclosporine every 12 hours on days -2 to 14. Patients may undergo autologous PBSC
transplantation, if necessary, no earlier than day 17 and receive G-CSF SC beginning at
the completion of PBSC re-infusion and continuing until blood counts recover.
- Cohort II: Patients undergo PBSC mobilization and receive treatment as in cohort I.
Patients also receive paclitaxel IV over 3 hours on day 9.
- Cohort III: Patients undergo PBSC mobilization and receive unlabeled MOAB Lym-1, In111
MOAB Lym-1, Y90 MOAB Lym-1, and cyclosporine as in cohort I and paclitaxel as in cohort
II. Patients undergo autologous PBSC transplantation no earlier than day 17. Patients
receive G-CSF after transplantation as in cohort I.
- Cohort IV: Patients undergo PBSC mobilization and receive treatment as in cohort III.
Treatment repeats every 6 weeks for 2 courses in the absence of disease progression or
unacceptable toxicity.
Cohorts of 1 to 3 patients receive escalating doses of Y90 MOAB Lym-1 until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose at which 1 of 3 patients
require PBSC transplantation, or the dose preceding that at which 2 of 3 patients experience
dose-limiting toxicity.
Patients are followed monthly for 3 months, every 3 months for 1 year, every 6 months for 1
year, and then annually thereafter.
PROJECTED ACCRUAL: A maximum of 40 patients will be accrued for this study within 36 months.
Overall Status
Unknown status
Start Date
2001-02-01
Completion Date
N/A
Primary Completion Date
N/A
Phase
Phase 1
Study Type
Interventional
Condition
Intervention
Eligibility
Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed non-Hodgkin's lymphoma (NHL) that has failed standard therapy
- Any grade allowed
- Intermediate or high grade NHL must have failed standard therapy with curative
intent
- Measurable disease
- HAMA titer negative
- NHL tissue Lym-1 reactive in vitro
- Bilateral bone marrow biopsy less than 25% NHL
- No evidence of myelodysplastic syndrome in bone marrow NOTE: A new classification
scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of
"indolent" or "aggressive" lymphoma will replace the former terminology of "low",
"intermediate", or "high" grade lymphoma. However, this protocol uses the former
terminology.
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- Karnofsky 70-100%
Life expectancy:
- Not specified
Hematopoietic:
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 130,000/mm^3
Hepatic:
- Bilirubin no greater than 1.5 mg/dL
- AST no greater than 84 U/L
Renal:
- Creatinine less than 1.5 mg/dL OR
- Creatinine clearance at least 50 mL/min
Cardiovascular:
- LVEF at least 50%
Pulmonary:
- FEV1 at least 60% of predicted
- FVC at least 60% of predicted
- Corrected DLCO at least 50%
Other:
- No other malignancy within the past 5 years except for non- melanoma skin cancer
- HIV negative
- No AIDS
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- At least 4 weeks since prior chemotherapy
Endocrine therapy:
- Not specified
Radiotherapy:
- No prior radiotherapy involving more than 25% of bone marrow
- At least 4 weeks since prior external beam radiotherapy
Surgery:
- Not specified
Gender
All
Minimum Age
18 Years
Maximum Age
N/A
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
|
Gerald L. DeNardo, MD |
Study Chair |
University of California, Davis |
Location
Facility |
|
University of California Davis Cancer Center Sacramento California 95817 United States |
Location Countries
Country
United States
Verification Date
2002-12-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Keywords
recurrent grade 1 follicular lymphoma 
, recurrent grade 2 follicular lymphoma , recurrent grade 3 follicular lymphoma , recurrent adult diffuse small cleaved cell lymphoma , recurrent adult diffuse mixed cell lymphoma , recurrent adult diffuse large cell lymphoma , recurrent adult immunoblastic large cell lymphoma , recurrent adult lymphoblastic lymphoma , recurrent adult Burkitt lymphoma , recurrent mantle cell lymphoma , recurrent marginal zone lymphoma , recurrent small lymphocytic lymphoma , extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue , nodal marginal zone B-cell lymphoma , splenic marginal zone lymphoma
, recurrent grade 2 follicular lymphoma , recurrent grade 3 follicular lymphoma , recurrent adult diffuse small cleaved cell lymphoma , recurrent adult diffuse mixed cell lymphoma , recurrent adult diffuse large cell lymphoma , recurrent adult immunoblastic large cell lymphoma , recurrent adult lymphoblastic lymphoma , recurrent adult Burkitt lymphoma , recurrent mantle cell lymphoma , recurrent marginal zone lymphoma , recurrent small lymphocytic lymphoma , extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue , nodal marginal zone B-cell lymphoma , splenic marginal zone lymphoma Has Expanded Access
No
Condition Browse
Secondary Id
CDR0000068363
NCI-V00-1638
Intervention Browse
Mesh Term
Cyclosporine
Paclitaxel
Albumin-Bound Paclitaxel
Antineoplastic Agents, Immunological
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Cyclosporins
Firstreceived Results Date
N/A
Firstreceived Results Disposition Date
N/A
Study Design Info
Primary Purpose
Treatment
Masking
None (Open Label)
Study First Submitted
January 6, 2001
Study First Submitted Qc
May 30, 2003
Study First Posted
June 2, 2003
Last Update Submitted
August 6, 2013
Last Update Submitted Qc
August 6, 2013
Last Update Posted
August 7, 2013
Last Known Status
Active, not recruiting
ClinicalTrials.gov processed this data on December 06, 2019
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.