Iodine I 131 Monoclonal Antibody BC8 Before Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00860171
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 16
• Location: 1
• Arm: 1
• Duration (Months): 133.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This phase I trial studies the side effects and best dose of iodine I 131 monoclonal antibody BC8 when given before autologous stem cell transplant in treating patients with Hodgkin lymphoma or non-Hodgkin lymphoma that has returned after a period of improvement or does not respond to treatment. Radiolabeled monoclonal antibodies, such as iodine I 131 monoclonal antibody BC8, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Giving iodine I 131 monoclonal antibody BC8 before an autologous stem cell transplant may kill more cancer cells.

Condition or Disease	Intervention/Treatment	Phase
Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma	Procedure: Autologous Hematopoietic Stem Cell Transplantation; Radiation: Iodine I 131 Monoclonal Antibody BC8; Other: Laboratory Biomarker Analysis	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

1. To estimate the maximally tolerated dose of 131I-BC8 (anti-cluster of differentiation [CD]45) (iodine I 131 monoclonal antibody BC8) that can be delivered prior to autologous stem cell transplantation for patients with relapsed/refractory B-non-Hodgkin lymphoma (NHL), T-NHL, or Hodgkin lymphoma (HL).

SECONDARY OBJECTIVES:

1. To optimize the protein dose (antibody [Ab]) to deliver a favorable biodistribution in the majority of patients.

2. To assess the radiation dose delivered to tumor sites and normal organs by the above therapy.

3. To evaluate the dose-response relationship of radiation-dose to tumor and clinical response.

4. To estimate the overall and progression-free survival of the above regimen in such patients.

5. To evaluate the toxicity and tolerability of the above therapy.

6. To evaluate the feasibility of delivering high-dose 131I-BC8 and autologous stem cell transplantation (ASCT) to B-Cell NHL, T-NHL, and HL patients.

7. To evaluate the ability to reduce infusion reactions via unlabeled BC8 preinfusion.

OUTLINE: This is a dose-escalation study.

Patients receive a dosimetric dose of iodine I 131 monoclonal antibody BC8 intravenously (IV) on day -20 and a therapeutic dose on day -11. Before day -20, patients may also receive up to 2 additional dosimetric doses of iodine I 131 monoclonal antibody BC8 IV approximately 1-2 weeks apart. Patients then undergo autologous stem cell transplantation on day 0.

After completion of study treatment, patients are followed up at 1, 3, 6, and 12 months and then annually thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: A single site, open label clinical trial.A single site, open label clinical trial.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Study Evaluating Escalating Doses of 131I-BC8 (Anti-CD45) Antibody Followed by Autologous Stem Cell Transplantation for Relapsed or Refractory Lymphoid Malignancies
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Mar 1, 2015
• Actual Study Completion Date: Mar 21, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (iodine I 131 monoclonal antibody B, autologous HCT) Patients receive a dosimetric dose of iodine I 131 monoclonal antibody BC8 IV on day -20 and a therapeutic dose on day -11. Before day -20, patients may also receive up to 2 additional dosimetric doses of iodine I 131 monoclonal antibody BC8 IV approximately 1-2 weeks apart. Patients then undergo autologous stem cell transplantation on day 0.

Procedure: Autologous Hematopoietic Stem Cell Transplantation; Autologous stem cells given via central catheter; Other Names: Autologous Stem Cell Transplantation ; Radiation: Iodine I 131 Monoclonal Antibody BC8; Given IV; Other Names: I 131 MOAB BC8 I 131 Monoclonal Antibody BC8 iodine I 131 MOAB BC8 MOAB BC8, iodine I 131 monoclonal antibody BC8, iodine I 131 ; Other: Laboratory Biomarker Analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose (MTD) of I-131-BC8 That Can be Delivered Prior to Transplant [Within 30 days post-transplant]

   Dose escalation/de-escalation will be conducted by the "two-stage" approach introduced by Storer. Escalation will continue until a dose-limiting toxicity (DLT) occurs. A DLT will be defined as a therapy-related grade III or IV Bearman (transplant) toxicity. The MTD is estimated to be the dose that is associated with a toxicity rate of 25% (Bearman grade 3-4).

2. I-131 Activity Administered [At time of I-131 therapy]

Secondary Outcome Measures

1. Adverse Events [Up to 6 years]

   Descriptive statistics will be calculated. DLT will be defined by the Bearman Scale that is designed to address the specific toxicities associated with transplantation.

2. Overall Survival [Up to 6 years]

3. Progression-free Survival [Up to 6 years]

   number of people with progression free survival

4. Relapse Rate [Up to 6 years]

   Number of relapse

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have a histologically confirmed diagnosis of B-NHL, T-NHL, or HL; CD45 antigen expression must be documented on tumor specimens in all cases except HL, in whom histologic demonstration of CD45+ cells adjacent to the Reed Sternberg cells is required

• Patients must have received at least one prior standard systemic therapy with documented recurrent or refractory disease

• Mantle cell lymphoma (MCL), T-NHL, or other high-risk malignancies may be enrolled/transplanted in complete remission (CR)/first partial remission (PR1)

• Patients are preferred to have either a tumor mass amenable to core needle biopsy during the dosimetry phase, or a measurable tumor mass with at least one site of involvement measuring 2.0 cm in largest dimension on computed tomography (CT) imaging for purposes of planar and/or single-photon emission CT (SPECT)/CT tumor dosimetry (patients with disease that does not allow tumor dosimetry will be allowed on study since they still can contribute toward achieving the primary endpoint, but these patients will be given a lower priority over those with evaluable disease)

• Creatinine [Cr] < 2.0

• Bilirubin < 1.5 mg/dL, with the exception of patients thought to have Gilbert's syndrome, who may have a total bilirubin above 1.5 mg/dL

• All patients eligible for therapeutic study must have a minimum of >= 4 x10^{6 CD34/kg autologous hematopoietic stem cells harvested and cryopreserved and divided into 2 aliquots of at least >= 2 x10}6 CD34/kg each; patients with a history of prior autologous hematopoietic cell transplant (HCT) are only required to have >= 2x10^6 CD34/kg stored

• Patients must have an expected survival of > 60 days and must be free of major infection

Exclusion Criteria:

• Circulating human anti-mouse antibody (HAMA), to be determined before each infusion

• Systemic anti-lymphoma therapy given in the previous 30 days before the scheduled therapy dose with the exception of rituximab

• Inability to understand or give an informed consent

• Lymphoma involving the central nervous system

• Other serious medical conditions considered to represent contraindications to bone marrow transplant (BMT) (e.g. abnormally decreased cardiac ejection fraction, diffusion capacity of the lung for carbon monoxide (DLCO) < 50% predicted, forced expiratory volume in one second (FEV1) < 70% predicted, acquired immune deficiency syndrome [AIDS], etc.)

• Known human immunodeficiency virus (HIV) seropositivity

• Pregnancy or breast feeding

• Prior allogeneic bone marrow or stem cell transplant

• Prior autologous bone marrow or stem cell transplant or prior radiation therapy (RT) > 20 Gy to a critical organ within 1 year of enrollment

• Presence of circulating lymphoma cells by morphology or flow cytometry (> 0.1%) at or near the time of peripheral blood stem cell (PBSC) collection if unpurged/unselected PBSC are to be used (patients with cryopreserved stem cells which are negative [=< 0.1% involved] by flow cytometry will also be considered eligible)

• Southwest Oncology Group (SWOG) performance status >= 2.0

• Unable to perform self-care during radiation isolation

• Expected survival if untreated less than 60 days

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Fred Hutchinson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Ajay Gopal, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT00860171
• Other Study ID Numbers: 2238.00; NCI-2010-00128; 2238.00; P01CA044991; P30CA015704
• First Posted: Mar 12, 2009
• Last Update Posted: Apr 3, 2020
• Last Verified: Aug 1, 2019

• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Hodgkin Disease; Lymphoma, B-Cell; Lymphoma, T-Cell; Recurrence; Iodine; Cadexomer iodine; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	Treatment (Iodine I 131 Monoclonal Antibody B, Autologous HCT)
Arm/Group Description	Patients receive a dosimetric dose of iodine I 131 monoclonal antibody BC8 IV on day -20 and a therapeutic dose on day -11. Before day -20, patients may also receive up to 2 additional dosimetric doses of iodine I 131 monoclonal antibody BC8 IV approximately 1-2 weeks apart. Patients then undergo autologous stem cell transplantation on day 0. Autologous Hematopoietic Stem Cell Transplantation: Autologous stem cells given via central catheter Iodine I 131 Monoclonal Antibody BC8: Given IV Laboratory Biomarker Analysis: Correlative studies
Period Title: Overall Study
STARTED	16
COMPLETED	16
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Iodine I 131 Monoclonal Antibody B, Autologous HCT)
Arm/Group Description	Patients receive a dosimetric dose of iodine I 131 monoclonal antibody BC8 IV on day -20 and a therapeutic dose on day -11. Before day -20, patients may also receive up to 2 additional dosimetric doses of iodine I 131 monoclonal antibody BC8 IV approximately 1-2 weeks apart. Patients then undergo autologous stem cell transplantation on day 0. Autologous Hematopoietic Stem Cell Transplantation: Autologous stem cells given via central catheter Iodine I 131 Monoclonal Antibody BC8: Given IV Laboratory Biomarker Analysis: Correlative studies
Overall Participants	16
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.81 (15.63)
Sex: Female, Male (Count of Participants)
Female	6 37.5%
Male	10 62.5%
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	16 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	16 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of I-131-BC8 That Can be Delivered Prior to Transplant
Description	Dose escalation/de-escalation will be conducted by the "two-stage" approach introduced by Storer. Escalation will continue until a dose-limiting toxicity (DLT) occurs. A DLT will be defined as a therapy-related grade III or IV Bearman (transplant) toxicity. The MTD is estimated to be the dose that is associated with a toxicity rate of 25% (Bearman grade 3-4).
Time Frame	Within 30 days post-transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Iodine I 131 Monoclonal Antibody B, Autologous HCT)
Arm/Group Description	Patients receive a dosimetric dose of iodine I 131 monoclonal antibody BC8 IV on day -20 and a therapeutic dose on day -11. Before day -20, patients may also receive up to 2 additional dosimetric doses of iodine I 131 monoclonal antibody BC8 IV approximately 1-2 weeks apart. Patients then undergo autologous stem cell transplantation on day 0. Autologous Hematopoietic Stem Cell Transplantation: Autologous stem cells given via central catheter Iodine I 131 Monoclonal Antibody BC8: Given IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	16
Number [Gray of I-131 (absorbed dose that the I]	NA

2. Primary Outcome

Title	I-131 Activity Administered
Time Frame	At time of I-131 therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Iodine I 131 Monoclonal Antibody B, Autologous HCT)
Arm/Group Description	Patients receive a dosimetric dose of iodine I 131 monoclonal antibody BC8 IV on day -20 and a therapeutic dose on day -11. Before day -20, patients may also receive up to 2 additional dosimetric doses of iodine I 131 monoclonal antibody BC8 IV approximately 1-2 weeks apart. Patients then undergo autologous stem cell transplantation on day 0. Autologous Hematopoietic Stem Cell Transplantation: Autologous stem cells given via central catheter Iodine I 131 Monoclonal Antibody BC8: Given IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	16
Mean (Full Range) [mCi I-131]	668.15

3. Secondary Outcome

Title	Adverse Events
Description	Descriptive statistics will be calculated. DLT will be defined by the Bearman Scale that is designed to address the specific toxicities associated with transplantation.
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Iodine I 131 Monoclonal Antibody B, Autologous HCT)
Arm/Group Description	Patients receive a dosimetric dose of iodine I 131 monoclonal antibody BC8 IV on day -20 and a therapeutic dose on day -11. Before day -20, patients may also receive up to 2 additional dosimetric doses of iodine I 131 monoclonal antibody BC8 IV approximately 1-2 weeks apart. Patients then undergo autologous stem cell transplantation on day 0. Autologous Hematopoietic Stem Cell Transplantation: Autologous stem cells given via central catheter Iodine I 131 Monoclonal Antibody BC8: Given IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	16
Number [number of adverse events]	0

4. Secondary Outcome

Title	Overall Survival
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Iodine I 131 Monoclonal Antibody B, Autologous HCT)
Arm/Group Description	Patients receive a dosimetric dose of iodine I 131 monoclonal antibody BC8 IV on day -20 and a therapeutic dose on day -11. Before day -20, patients may also receive up to 2 additional dosimetric doses of iodine I 131 monoclonal antibody BC8 IV approximately 1-2 weeks apart. Patients then undergo autologous stem cell transplantation on day 0. Autologous Hematopoietic Stem Cell Transplantation: Autologous stem cells given via central catheter Iodine I 131 Monoclonal Antibody BC8: Given IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	16
Mean (Standard Deviation) [days]	1057 (633.59)

5. Secondary Outcome

Title	Progression-free Survival
Description	number of people with progression free survival
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Iodine I 131 Monoclonal Antibody B, Autologous HCT)
Arm/Group Description	Patients receive a dosimetric dose of iodine I 131 monoclonal antibody BC8 IV on day -20 and a therapeutic dose on day -11. Before day -20, patients may also receive up to 2 additional dosimetric doses of iodine I 131 monoclonal antibody BC8 IV approximately 1-2 weeks apart. Patients then undergo autologous stem cell transplantation on day 0. Autologous Hematopoietic Stem Cell Transplantation: Autologous stem cells given via central catheter Iodine I 131 Monoclonal Antibody BC8: Given IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	16
Count of Participants [Participants]	5 31.3%

6. Secondary Outcome

Title	Relapse Rate
Description	Number of relapse
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Iodine I 131 Monoclonal Antibody B, Autologous HCT)
Arm/Group Description	Patients receive a dosimetric dose of iodine I 131 monoclonal antibody BC8 IV on day -20 and a therapeutic dose on day -11. Before day -20, patients may also receive up to 2 additional dosimetric doses of iodine I 131 monoclonal antibody BC8 IV approximately 1-2 weeks apart. Patients then undergo autologous stem cell transplantation on day 0. Autologous Hematopoietic Stem Cell Transplantation: Autologous stem cells given via central catheter Iodine I 131 Monoclonal Antibody BC8: Given IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	16
Count of Participants [Participants]	5 31.3%

Adverse Events

Arm/Group Title	Treatment (Iodine I 131 Monoclonal Antibody B, Autologous HCT)
Arm/Group Description	Patients receive a dosimetric dose of iodine I 131 monoclonal antibody BC8 IV on day -20 and a therapeutic dose on day -11. Before day -20, patients may also receive up to 2 additional dosimetric doses of iodine I 131 monoclonal antibody BC8 IV approximately 1-2 weeks apart. Patients then undergo autologous stem cell transplantation on day 0. Autologous Hematopoietic Stem Cell Transplantation: Autologous stem cells given via central catheter Iodine I 131 Monoclonal Antibody BC8: Given IV Laboratory Biomarker Analysis: Correlative studies
All Cause Mortality
	Treatment (Iodine I 131 Monoclonal Antibody B, Autologous HCT)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Iodine I 131 Monoclonal Antibody B, Autologous HCT)
	Affected / at Risk (%)	# Events
Total	3/16 (18.8%)
Gastrointestinal disorders
Mucositis/stomatitis	1/16 (6.3%)	1
General disorders
Fever	1/16 (6.3%)	1
Respiratory, thoracic and mediastinal disorders
dyspnea	1/16 (6.3%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Iodine I 131 Monoclonal Antibody B, Autologous HCT)
	Affected / at Risk (%)	# Events
Total	0/16 (0%)

Limitations/Caveats

This protocol was closed to enrollment when replaced by a newer approach.

More Information

Certain Agreements

All Principal Investigators ARE 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.