NCT00984165

Pilot Study of Radiation-Enhanced Allogeneic Cell Therapy for Progressive Hematologic Malignancy After Allogeneic Hematopoietic Stem Cell Transplantation

Terminated Phase 2 Results posted Last updated 2 May 2018

What this trial tests

Phase 2 trial testing Single fraction radiation in Hodgkin's Lymphoma in 18 participants. Terminated before completion.

Timeline

19 January 2010

Primary endpoint
18 January 2013

31 January 2013

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	18
Start date	19 January 2010
Primary completion	18 January 2013
Estimated completion	31 January 2013
Sites	1 location across United States

Drugs / interventions tested

• Single fraction radiation
• Donor Lymphocyte Infusion (DLI) — full drug profile →
• Apheresis

Conditions studied

• Hodgkin's Lymphoma — all drugs for Hodgkin's Lymphoma →
• Non-Hodgkin's Lymphoma — all drugs for Non-Hodgkin's Lymphoma →
• Chronic Lymphocytic Leukemias — all drugs for Chronic Lymphocytic Leukemias →
• Multiple Myeloma With Plasmacytoma — all drugs for Multiple Myeloma With Plasmacytoma →

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 18 to 75, any sex, with Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Response to Graft Versus Host Disease (GVHD) Treatment Primary · Up to 100 days

The following criteria is used to determine response to GVHD treatment. Complete response (CR) is complete resolution of all clinical signs and symptoms of acute GVHD. Partial response (PR) is 50% reduction in skin rash, stool volume or frequency, and/or total bilirubin. Failure to maintain adequate performance status (Karnofsky Score \>/= 70%). Non-responder (NR) \<50% reduction in skin rash, stool volume or frequency, and/or total bilirubin. Failure to maintain adequate performance status (Karnofsky Score \</= 70%). Progressive disease (PD) is further progression of signs and symptoms of acu

Complete Response (CR)

Group	Value	95% CI
Donor Lymphocyte Infusion/Radiation	0
Radiation/No Donor Lymphocyte Infusion	0
Donor Lymphocyte Infusion-Control	0

Partial Response (PR)

Group	Value	95% CI
Donor Lymphocyte Infusion/Radiation	1
Radiation/No Donor Lymphocyte Infusion	0
Donor Lymphocyte Infusion-Control	0

Non-responder (NR)

Group	Value	95% CI
Donor Lymphocyte Infusion/Radiation	6
Radiation/No Donor Lymphocyte Infusion	1
Donor Lymphocyte Infusion-Control	3

Progressive Disease (PD)

Group	Value	95% CI
Donor Lymphocyte Infusion/Radiation	2
Radiation/No Donor Lymphocyte Infusion	0
Donor Lymphocyte Infusion-Control	1

Number of Participants With Adverse Events Secondary · Date treatment consent signed to date off study, approximately 36 months.

Here is the number of participants with adverse events. For the detailed list of adverse events, see the adverse event module.

Group	Value	95% CI
Donor Lymphocyte Infusion/Radiation	9
Radiation/No Donor Lymphocyte Infusion	1
Donor Lymphocyte Infusion - Control	4
Donor Lymphocyte Infusion - Donor	0

Adverse events — posted to ClinicalTrials.gov

Time frame: Date treatment consent signed to date off study, approximately 36 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Donor Lymphocyte Infusion/Radiation

Serious: 4/9 (44%)

Deaths: 0/9

Radiation/No Donor Lymphocyte Infusion

Serious: 0/1 (0%)

Deaths: 0/1

Donor Lymphocyte Infusion - Control

Serious: 0/4 (0%)

Deaths: 0/4

Donor Lymphocyte Infusion - Donor

Serious: 0/4 (0%)

Deaths: 0/4

Serious adverse events (22 terms)

Reaction	System	Donor Lymphocyte Infusion/…	Radiation/No Donor Lymphoc…	Donor Lymphocyte Infusion …	Donor Lymphocyte Infusion …
Hypoxia	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Lung infection	Infections and infestations	—	—	—	—
Acidosis	Metabolism and nutrition disorders	—	—	—	—
Acute kidney injury	Renal and urinary disorders	—	—	—	—
Anemia	Blood and lymphatic system disorders	—	—	—	—
Ascites	Gastrointestinal disorders	—	—	—	—
Bronchopulmonary hemorrhage	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Confusion	Psychiatric disorders	—	—	—	—
Delirium	Psychiatric disorders	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
General disorders and administration site conditions - Other, specify (coma)	General disorders	—	—	—	—
Infections and infestations - Other, specify (aspergillis (+) in sputum)	Infections and infestations	—	—	—	—
Infections and infestations - Other, specify (sputum, pseudomonas (+))	Infections and infestations	—	—	—	—
Laryngeal edema	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Left ventricular systolic dysfunction	Cardiac disorders	—	—	—	—
Lethargy	Nervous system disorders	—	—	—	—
Multi-organ failure	General disorders	—	—	—	—
Neutrophil count decreased	Investigations	—	—	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Pleural infection	Infections and infestations	—	—	—	—
Pulmonary edema	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Sinus tachycardia	Cardiac disorders	—	—	—	—

Other adverse events (63 terms — click to expand)

Reaction	System	Donor Lymphocyte Infusion/…	Radiation/No Donor Lymphoc…	Donor Lymphocyte Infusion …	Donor Lymphocyte Infusion …
Anemia	Blood and lymphatic system disorders	—	—	—	—
Hypoalbuminemia	Metabolism and nutrition disorders	—	—	—	—
Neutrophil count decreased	Investigations	—	—	—	—
White blood cell decreased	Investigations	—	—	—	—
Activated partial thromboplastin time prolonged	Investigations	—	—	—	—
Alkaline phosphatase increased	Investigations	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—
Hypomagnesemia	Metabolism and nutrition disorders	—	—	—	—
Lymphocyte count decreased	Investigations	—	—	—	—
Platelet count decreased	Investigations	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—
Fatigue	General disorders	—	—	—	—
Hypocalcemia	Metabolism and nutrition disorders	—	—	—	—
Hypophosphatemia	Metabolism and nutrition disorders	—	—	—	—
Pain	General disorders	—	—	—	—
Blood bilirubin increased	Investigations	—	—	—	—
Creatinine increased	Investigations	—	—	—	—
Fever	General disorders	—	—	—	—
Hypercalcemia	Metabolism and nutrition disorders	—	—	—	—
Hyperkalemia	Metabolism and nutrition disorders	—	—	—	—
Hypermagnesemia	Metabolism and nutrition disorders	—	—	—	—
Hypernatremia	Metabolism and nutrition disorders	—	—	—	—
Hypokalemia	Metabolism and nutrition disorders	—	—	—	—
Hyponatremia	Metabolism and nutrition disorders	—	—	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—
Alkalosis	Metabolism and nutrition disorders	—	—	—	—
Anorexia	Metabolism and nutrition disorders	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Bronchospasm	Respiratory, thoracic and mediastinal disorders	—	—	—	—
CPK increased	Investigations	—	—	—	—
Chills	General disorders	—	—	—	—
Confusion	Psychiatric disorders	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Dermatitis radiation	Injury, poisoning and procedural complications	—	—	—	—
Dry eye	Eye disorders	—	—	—	—
Dysphagia	Gastrointestinal disorders	—	—	—	—
Ear and labyrinth disorders - Other, specify (b/l ear fullness)	Ear and labyrinth disorders	—	—	—	—
Flu like symptoms	General disorders	—	—	—	—
Haptoglobin decreased	Investigations	—	—	—	—

Most-reported serious reactions: Hypoxia, Lung infection, Acidosis, Acute kidney injury, Anemia, Ascites, Bronchopulmonary hemorrhage, Confusion.

Data from ClinicalTrials.gov NCT00984165 adverse events section.

Sponsor's own description

Background:

* Allogeneic hematopoietic stem cell transplantation (allotransplant) has been used to treat many kinds of cancer that develop in cells from the blood or immune system. After allotransplant, donor cells take over production of the recipient s blood and immune cells, and donor immune cells can directly attack and control tumor. However, for cancers that do not respond to allotransplant, there are no proven cures.
* A single treatment with radiation can improve the potency of immune-cell therapies. This is probably because the tumor tissue is damaged in a way that new tumor proteins are exposed, attracting immune cells to the tumor. By giving only a single dose of radiation, the immune cells that are attracted to the tumor are allowed to survive and function in their usual way, traveling throughout the body and educating other immune cells to recognize tumor, and to activate and expand in order to kill the tumor cells. Some research has shown that radiation may have a widespread effect on stimulating the immune system, educating immune cells to recognize and control tumors that have not been radiated.

Objectives:

\- To determine whether a single treatment of radiation will help donor immune cells control cancer after allotransplant without causing excessive side effects.

Eligibility:

* Recipients: Individuals 18 years of age and older who have blood cancers that have not responded to allotransplant.
* Donors: Healthy individuals 18 years of age and older who were previous allotransplant donors for one of the study recipients.

Design:

* Donors will provide additional blood immune cells, called lymphocytes, through apheresis. Apheresis involves drawing blood, separating out the lymphocytes, and returning the rest of the blood to the donor.
* Recipients will receive a single dose of radiation to the greatest amount of tumor that can be irradiated safely. Researchers will intentionally leave some tumor that will not be radiated in order to evaluate whether there is a widespread response to the treatment.
* There are two treatment arms on the study.
* Arm 1: Study participants who have donor lymphocytes available and who have not had major complications from the allotransplant will be given a dose of donor cells after they receive radiation, to provide an additional boost to the donor immune response.
* Arm 2: Study participants who cannot receive donor lymphocytes because their donor is not available, they received an allotransplant from a partially matched relative, or they have had significant complications from the allotransplant - will receive radiation without additional donor lymphocytes.
* All recipients will be followed closely for side effects and for tumor response to radiation with or without donor lymphocytes. Additional tests will be performed, including tumor biopsies, bone marrow samples, and blood draws, in order to study the immune effects of radiation and donor lymphocytes.
* A separate, control group of allotransplant recipients will not receive radiation. This group will include participants whose transplant doctors plan to use donor lymphocyte therapy alone to control cancer progression. This group will donate blood immune cells through blood draws and apheresis. These cells will be examined to study the immune effects of receiving donor lymphocytes without radiation.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Proceedings from the National Cancer Institute's Second International Workshop on the Biology, Prevention, and Treatment of Relapse After Hematopoietic Stem Cell Transplantation: part III. Prevention and treatment of relapse after allogeneic transplantation.
   de Lima M, Porter DL, Battiwalla M, Bishop MR, et al · · 2014 · cited 115× · PMID 24018392 · DOI 10.1016/j.bbmt.2013.08.012