Intensity Modulated Total Marrow Irradiation (IM-TMI) for Advanced Hematologic Malignancies

• Sponsor: University of Illinois at Chicago (Other)
• Overall Status: Completed
• CT.gov ID: NCT00988013
• Collaborator: (none)
• Enrollment: 14
• Location: 1
• Arms: 4
• Duration (Months): 77
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a phase I study using Intensity Modulated Total Marrow Irradiation (IM-TMI) in addition to a chemotherapy regimen in preparation for an allogeneic stem cell transplant for advanced hematologic malignancies such as acute myeloid or lymphoblastic leukemia, high grade non Hodgkin's or Hodgkin's lymphoma, chronic myelogenous leukemia, and plasma cell leukemia. Because the subjects participating in this study have a disease that is severe and has a high risk of relapse even after transplant, the investigators propose to use a chemotherapy regimen (fludarabine/busulfan), the name for the combination of chemotherapy drugs that is given to patients prior to transplantation of the donor stem cells, along with intensity modulated radiation (IM-TMI) to the bone marrow. Total body irradiation (TBI) in conjunction with chemotherapy is a standard of care as a pre-conditioning regimen prior to bone marrow transplant (BMT) in patients with hematologic malignancies. However, TBI can cause severe side effects due to irradiation of organs such as the lenses of the eye, whole brain, lungs, liver, kidneys, heart, small bowel and oral cavity. IM-TMI allows for the delivery of adequate doses of radiation to the bone marrow while sparing other organs and therefore limiting radiation side effects. The irradiation, along with receiving the chemotherapy drugs will suppress the subject's immune system and kill off tumor cells, but will also intensify the effect of the conditioning regimen thus allowing the bone marrow transplantation to have a greater chance of being successful.

No investigational drugs are used in this study. The investigational part of this study is the use of intensity modulated total marrow irradiation instead of conventional radiation. IMTMI can deliver 99% of the prescribed treatment to the targeted bones and reduce the doses of radiation to surrounding organs, as received in conventional TBI, by 29% to 65%.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia; Lymphoblastic Leukemia; Acute Leukemia; Non Hodgkins Lymphoma; Chronic Myeloid Leukemia	Radiation: IM-TMI (3Gy); Radiation: IM-TMI (6Gy); Radiation: IM-TMI (9Gy); Radiation: IM-TMI (12Gy)	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Intervention Model Description: Dose escalation of total marrow irradiation prior to stem cell transplantationDose escalation of total marrow irradiation prior to stem cell transplantation
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Study of Intensity Modulated Total Marrow Irradiation (IM-TMI) in Addition to Fludarabine/Busulfan Conditioning for Allogeneic Transplantation for Advanced Hematologic Malignancies
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Feb 1, 2016
• Actual Study Completion Date: Feb 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IM-TMI (3Gy) Patients will receive 3Gy per day for 1 day (total of 3Gy).	Radiation: IM-TMI (3Gy); Patients will receive 3Gy per day for 1 day.
Experimental: IM-TMI (6Gy) Patients will receive 3Gy per day for 2 days (for a total of 6Gy).	Radiation: IM-TMI (6Gy); Patients will receive 3Gy per day for 2 days.
Experimental: IM-TMI (9Gy) Patients will receive 3Gy per day for 3 days (for a total of 9Gy).	Radiation: IM-TMI (9Gy); Patients will receive 3Gy per day for 3 days.
Experimental: IM-TMI (12Gy) Patients will receive 3Gy per day for 4 days (for a total of 12Gy).	Radiation: IM-TMI (12Gy); Patients will receive 3Gy per day for 4 days.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Grade 4 TMI Toxicity [1 year post-transplant]

2. Number of Participants With 1 Year Mortality Unrelated to TMI [1 year post-transplant]

Secondary Outcome Measures

1. Time to Neutrophil and Platelet Engraftment in Patients With Hematologic Malignancies [Up to 100 days post-transplant]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with the following diseases:

• Acute myeloid or lymphoblastic leukemia in first complete remission if poor prognosis documented by failure to response after initial induction chemotherapy, or cytogenetic, or molecular studies.

• Acute leukemia in greater/equal second remission, or partial remission after chemotherapy.

• High grade non Hodgkin's or Hodgkin's lymphoma with marrow involvement resistant/ relapsed after second line therapy including high dose chemotherapy and autologous SCT.

• CML in advanced or blastic phase.

• Plasma cell leukemia.

• Age 18-60 years.

• Karnofsky performance status of 70

• Adequate cardiac and pulmonary function. Patients with decreased LVEF less than/equal to 40% or DLCO less than/equal to 50% of predicted will require clearance from cardiology or pulmonary services, respectively, prior to enrollment on this protocol.

• Serum creatinine less than/equal to 1.5 mg/dL or Creatinine Clearance greater than/equal to 50 ml/min .

• Serum bilirubin 2.0 mg/dl, SGPT less than/equal to 3 times the upper limit of normal

Exclusion Criteria:

• Life expectancy is severely limited by concomitant illness.

• Evidence of chronic active hepatitis or cirrhosis

• HIV-positive

• Patient is pregnant

• Patient or guardian is not able to sign informed consent.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Illinois at Chicago	Chicago	Illinois	United States	60612

Sponsors and Collaborators

• University of Illinois at Chicago

Investigators

• Study Chair: Damiano Rondelli, MD, University of Illinois at Chicago

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Damiano Rondelli, MD, Professor, University of Illinois at Chicago
• ClinicalTrials.gov Identifier: NCT00988013
• Other Study ID Numbers: 2009-0251
• First Posted: Oct 1, 2009
• Last Update Posted: Jun 14, 2021
• Last Verified: May 1, 2021

• Keywords provided by Damiano Rondelli, MD, Professor, University of Illinois at Chicago: total marrow irradiation; intensity modulated radiation; leukemia; hematologic diseases
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Hematologic Neoplasms; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Study Results

Participant Flow

Arm/Group Title	IM-TMI (3Gy)	IM-TMI (6Gy)	IM-TMI (9Gy)	IM-TMI (12Gy)
Arm/Group Description	Patients will receive 3Gy per day for 1 day (total of 3Gy). IM-TMI (3Gy): Patients will receive 3Gy per day for 1 day.	Patients will receive 3Gy per day for 2 days (for a total of 6Gy). IM-TMI (6Gy): Patients will receive 3Gy per day for 2 days.	Patients will receive 3Gy per day for 3 days (for a total of 9Gy). IM-TMI (9Gy): Patients will receive 3Gy per day for 3 days.	Patients will receive 3Gy per day for 4 days (for a total of 12Gy). IM-TMI (12Gy): Patients will receive 3Gy per day for 4 days.
Period Title: Overall Study
STARTED	3	3	6	2
COMPLETED	3	3	6	2
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	IM-TMI (3Gy)	IM-TMI (6Gy)	IM-TMI (9Gy)	IM-TMI (12Gy)	Total
Arm/Group Description	Patients will receive 3Gy per day for 1 day (total of 3Gy). IM-TMI (3Gy): Patients will receive 3Gy per day for 1 day.	Patients will receive 3Gy per day for 2 days (for a total of 6Gy). IM-TMI (6Gy): Patients will receive 3Gy per day for 2 days.	Patients will receive 3Gy per day for 3 days (for a total of 9Gy). IM-TMI (9Gy): Patients will receive 3Gy per day for 3 days.	Patients will receive 3Gy per day for 4 days (for a total of 12Gy). IM-TMI (12Gy): Patients will receive 3Gy per day for 4 days.	Total of all reporting groups
Overall Participants	3	3	6	2	14
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	3 100%	3 100%	6 100%	2 100%	14 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	52	38	39	53	52
Sex: Female, Male (Count of Participants)
Female	2 66.7%	2 66.7%	2 33.3%	1 50%	7 50%
Male	1 33.3%	1 33.3%	4 66.7%	1 50%	7 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 33.3%	1 33.3%	3 50%	1 50%	6 42.9%
Not Hispanic or Latino	0 0%	2 66.7%	0 0%	0 0%	2 14.3%
Unknown or Not Reported	2 66.7%	0 0%	3 50%	1 50%	6 42.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	1 33.3%	0 0%	0 0%	1 7.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	1 16.7%	0 0%	1 7.1%
White	3 100%	2 66.7%	4 66.7%	2 100%	11 78.6%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	1 16.7%	0 0%	1 7.1%
Region of Enrollment (Count of Participants)
United States	3 100%	3 100%	6 100%	2 100%	14 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Grade 4 TMI Toxicity
Time Frame	1 year post-transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IM-TMI (3Gy)	IM-TMI (6Gy)	IM-TMI (12Gy)	IM-TMI (9Gy)
Arm/Group Description	Patients will receive 3Gy per day for 1 day (total of 3Gy). IM-TMI (3Gy): Patients will receive 3Gy per day for 1 day.	Patients will receive 3Gy per day for 2 days (for a total of 6Gy). IM-TMI (6Gy): Patients will receive 3Gy per day for 2 days.	Patients will receive 3Gy per day for 3 days (for a total of 12Gy). IM-TMI (9Gy): Patients will receive 3Gy per day for 3 days.	Patients will receive 3Gy per day for 4 days (for a total of 9Gy). IM-TMI (12Gy): Patients will receive 3Gy per day for 4 days.
Measure Participants	3	3	6	2
Count of Participants [Participants]	0 0%	0 0%	0 0%	2 100%

2. Secondary Outcome

Title	Time to Neutrophil and Platelet Engraftment in Patients With Hematologic Malignancies
Time Frame	Up to 100 days post-transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IM-TMI (3Gy)	IM-TMI (6Gy)	IM-TMI (9Gy)	IM-TMI (12Gy)
Arm/Group Description	Patients will receive 3Gy per day for 1 day (total of 3Gy). IM-TMI (3Gy): Patients will receive 3Gy per day for 1 day.	Patients will receive 3Gy per day for 2 days (for a total of 6Gy). IM-TMI (6Gy): Patients will receive 3Gy per day for 2 days.	Patients will receive 3Gy per day for 3 days (for a total of 9Gy). IM-TMI (9Gy): Patients will receive 3Gy per day for 3 days.	Patients will receive 3Gy per day for 4 days (for a total of 12Gy). IM-TMI (12Gy): Patients will receive 3Gy per day for 4 days.
Measure Participants	3	3	6	2
Median (Full Range) [Days]	15	15	15	15

3. Primary Outcome

Title	Number of Participants With 1 Year Mortality Unrelated to TMI
Time Frame	1 year post-transplant

Outcome Measure Data

Analysis Population Description

Grade 4 TMI toxicity 0 Grade 4 TMI toxicity 0 Grade 4 TMI toxicity 0 Grade 4 TMI toxicity 0

Arm/Group Title	IM-TMI (3Gy)	IM-TMI (6Gy)	IM-TMI (9Gy)	IM-TMI (12Gy)
Arm/Group Description	Patients will receive 3Gy per day for 1 day (total of 3Gy). IM-TMI (3Gy): Patients will receive 3Gy per day for 1 day.	Patients will receive 3Gy per day for 2 days (for a total of 6Gy). IM-TMI (6Gy): Patients will receive 3Gy per day for 2 days.	Patients will receive 3Gy per day for 3 days (for a total of 9Gy). IM-TMI (9Gy): Patients will receive 3Gy per day for 3 days.	Patients will receive 3Gy per day for 4 days (for a total of 12Gy). IM-TMI (12Gy): Patients will receive 3Gy per day for 4 days.
Measure Participants	3	3	6	2
Count of Participants [Participants]	0 0%	0 0%	2 33.3%	2 100%

Adverse Events

Time Frame	7 years
Arm/Group Title	IM-TMI (3Gy)		IM-TMI (6Gy)		IM-TMI (9Gy)		IM-TMI (12Gy)
Arm/Group Description	Patients will receive 3Gy per day for 1 day (total of 3Gy). IM-TMI (3Gy): Patients will receive 3Gy per day for 1 day.		Patients will receive 3Gy per day for 2 days (for a total of 6Gy). IM-TMI (6Gy): Patients will receive 3Gy per day for 2 days.		Patients will receive 3Gy per day for 3 days (for a total of 9Gy). IM-TMI (9Gy): Patients will receive 3Gy per day for 3 days.		Patients will receive 3Gy per day for 4 days (for a total of 12Gy). IM-TMI (12Gy): Patients will receive 3Gy per day for 4 days.
All Cause Mortality
	IM-TMI (3Gy)		IM-TMI (6Gy)		IM-TMI (9Gy)		IM-TMI (12Gy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		0/3 (0%)		4/6 (66.7%)		2/2 (100%)
Serious Adverse Events
	IM-TMI (3Gy)		IM-TMI (6Gy)		IM-TMI (9Gy)		IM-TMI (12Gy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		2/6 (33.3%)		2/2 (100%)
Gastrointestinal disorders
GI hemorrhage	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/2 (50%)	1
Hepatobiliary disorders
Liver failure	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/2 (0%)	0
Infections and infestations
GVHD	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/2 (0%)	0
Pneumonia	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/2 (50%)	1
Bronchiolitis	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/2 (0%)	0
Other (Not Including Serious) Adverse Events
	IM-TMI (3Gy)		IM-TMI (6Gy)		IM-TMI (9Gy)		IM-TMI (12Gy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)		6/6 (100%)		2/2 (100%)
Gastrointestinal disorders
Gut mucocitis	0/3 (0%)	0	1/3 (33.3%)	1	1/6 (16.7%)	1	1/2 (50%)	1
Infections and infestations
Oral mucositis	3/3 (100%)	3	3/3 (100%)	3	6/6 (100%)	6	2/2 (100%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.