BMT-02: Total Marrow Irradiation With High Dose Melphalan Prior to Autologous Transplant for Multiple Myeloma

• Sponsor: University of Illinois at Chicago (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02043860
• Collaborator: (none)
• Enrollment: 3
• Location: 1
• Arm: 1
• Actual Duration (Months): 33.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

In this phase I trial, patients with multiple myeloma will receive standard high dose melphalan with autologous stem cell rescue. In addition the pre-transplant conditioning will include targeted total marrow irradiation (TMI). This conventional 3+3 phase I trial will increase the dose of TMI until the maximum tolerated dose (MTD) is reached. Initial patients enrolled will receive the lowest possible dose of 3Gy. Maximum dose will be 12Gy.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Radiation: Total Marrow Irradiation; Procedure: Autologous Transplant; Drug: Melphalan; Drug: Filgrastim (G-CSF)	Phase 1

Detailed Description

To establish the maximal tolerated dose of total marrow irradiation which can be added to high dose melphalan conditioning in patients with multiple myeloma undergoing autologous stem cell transplant.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: BMT-02: A Phase I Trial of Total Marrow Irradiation in Addition to High Dose Melphalan Conditioning Prior to Autologous Transplant for Multiple Myeloma Following Initial Induction Therapy
• Actual Study Start Date: Jan 10, 2014
• Actual Primary Completion Date: Nov 7, 2016
• Actual Study Completion Date: Nov 7, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Total Marrow Irradiation Escalating doses of total marrow irradiation (3Gy, 6Gy, 9Gy, or 12Gy) with standard high dose melphalan prior to autologous stem cell rescue.

Radiation: Total Marrow Irradiation; Subjects in this trial will receive total body irradiation (3Gy) per day for up to four days and as little as one day. Total IMT doses: 3Gy, 6Gy, 9Gy, or 12Gy.; Procedure: Autologous Transplant; Subjects will receive standard melphalan 200mg/m^2 (100mg/m^2 day-2 and day-1) conditioning with escalating doses of total marrow irradiation prior to autologous stem cell rescue.; Drug: Melphalan; Subjects will receive standard melphalan 200mg/m^2 (100mg/m^2 day-2 and day-1) conditioning therapy prior to transplant.; Other Names: Alkeran ® ; Drug: Filgrastim (G-CSF); Subjects to begin GCSF 5 μg/kg/d SC or IV on Day 5 and continue until ANC > 1000/mm^3 over period of 3 days.; Other Names: Neupogen®

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival No Results Due to 1 Subject Came Off Treatment Within 7 Days and 1 Subject Came Off Treatment Within 5 Days. Not Enough Data to Analyze [Up to 1 year post-transplant.]

   To evaluate progression free survival (PFS) and in patients with multiple myeloma undergoing autologous stem cell transplant using the combination of high dose melphalan and total marrow irradiation.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients meeting criteria for symptomatic myeloma

2. Patients must be high or intermediate risk of disease progression as defined by having one of the following criteria: 2.1 ISS stage 2 or 3 disease 2.2 Abnormal metaphase cytogenetics 2.3 Presence of FISH abnormalities aside from hyperdiploidy

3. Patients who have received at least 2 cycles of systemic treatment of any kind in the preceding 12 months

4. Patient age 18-75 years at time of enrollment

5. Karnofsky performance status of ≥70

6. Cardiac function: LVEF >40%

7. Hepatic: Bilirubin <2x upper limit of normal and ALT and AST < 2.5x the upper limit of normal

8. Renal: Creatinine clearance of ≥30mL/min, estimated or calculated

9. Pulmonary: DLCO, FEV1, FVC >50% of predicted (after correction for hemoglobin)

Exclusion Criteria:

1. Patients with diagnosis of plasma cell leukemia

2. Patients with myeloma who have had any disease progression prior to enrollment

3. Patients with truly non secretory myeloma (patients with light chain disease are eligible)

4. Pregnant or breast-feeding

5. Uncontrolled viral, fungal or bacterial infection Note: Infection is permitted if there is evidence of response to medication. Eligibility of HIV infected patients will be determined on a case-by-case basis.

6. Patients who have undergone prior allograft or autologous transplant

7. Prior solid organ transplant

8. Patients receiving prior radiation to more than 20% of bone marrow containing areas

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UIC Cancer Center	Chicago	Illinois	United States	60612

Sponsors and Collaborators

• University of Illinois at Chicago

Investigators

• Principal Investigator: Pritesh Patel, MD, University of Illinois at Chicago

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pritesh Patel, MD, Faculty, Assistant Professor, University of Illinois at Chicago
• ClinicalTrials.gov Identifier: NCT02043860
• Other Study ID Numbers: 2013-0202; 2013-0202
• First Posted: Jan 23, 2014
• Last Update Posted: Oct 14, 2019
• Last Verified: Sep 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Pritesh Patel, MD, Faculty, Assistant Professor, University of Illinois at Chicago: Multiple Myeloma; High Risk; Intermediate Risk; Symptomatic
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Melphalan

Study Results

Participant Flow

Recruitment Details	1 ineligible

Arm/Group Title	Total Marrow Irradiation
Arm/Group Description	Escalating doses of total marrow irradiation (3Gy(gray), 6Gy, 9Gy, or 12Gy) with standard high dose melphalan prior to autologous stem cell rescue. Total Marrow Irradiation (TMI): Subjects in this trial will receive total body irradiation (3Gy) per day for up to four days and as little as one day. Total IMT doses: 3Gy, 6Gy, 9Gy, or 12Gy. Autologous Transplant: Subjects will receive standard melphalan 200mg/m^2 (100mg/m^2 day-2 and day-1) conditioning with escalating doses of total marrow irradiation prior to autologous stem cell rescue. Melphalan: Subjects will receive standard melphalan 200mg/m^2 (100mg/m^2 day-2 and day-1) conditioning therapy prior to transplant. Filgrastim (G-CSF): Subjects to begin GCSF 5 μg/kg/d SC or IV on Day 5 and continue until ANC > 1000/mm^3 over period of 3 days.
Period Title: Overall Study
STARTED	2
COMPLETED	2
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Total Marrow Irradiation
Arm/Group Description	Escalating doses of total marrow irradiation (3Gy, 6Gy, 9Gy, or 12Gy) with standard high dose melphalan prior to autologous stem cell rescue. Total Marrow Irradiation: Subjects in this trial will receive total body irradiation (3Gy) per day for up to four days and as little as one day. Total IMT doses: 3Gy, 6Gy, 9Gy, or 12Gy. Autologous Transplant: Subjects will receive standard melphalan 200mg/m^2 (100mg/m^2 day-2 and day-1) conditioning with escalating doses of total marrow irradiation prior to autologous stem cell rescue. Melphalan: Subjects will receive standard melphalan 200mg/m^2 (100mg/m^2 day-2 and day-1) conditioning therapy prior to transplant. Filgrastim (G-CSF): Subjects to begin GCSF 5 μg/kg/d SC or IV on Day 5 and continue until ANC > 1000/mm^3 over period of 3 days.
Overall Participants	2
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 50%
>=65 years	1 50%
Sex: Female, Male (Count of Participants)
Female	1 50%
Male	1 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	2 100%
Unknown or Not Reported	0 0%
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	1 50%
White	1 50%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival No Results Due to 1 Subject Came Off Treatment Within 7 Days and 1 Subject Came Off Treatment Within 5 Days. Not Enough Data to Analyze
Description	To evaluate progression free survival (PFS) and in patients with multiple myeloma undergoing autologous stem cell transplant using the combination of high dose melphalan and total marrow irradiation.
Time Frame	Up to 1 year post-transplant.

Outcome Measure Data

Analysis Population Description

Data not collected

Arm/Group Title	Cohort 1 TMI Dose 3Gy
Arm/Group Description	Cohort 1 patients will receive standard high dose melphalan with autologous stem cell rescue. Plus TMI at a dose of 3Gy.
Measure Participants	0

Adverse Events

Time Frame	2 years
Arm/Group Title	Cohort 1 TMI Dose 3Gy
Arm/Group Description	This is a phase I trial. Patients will receive standard high dose melphalan with autologous stem cell rescue. In addition the pre-transplant conditioning will include targeted total marrow irradiation (TMI). The dose of TMI will increase until the maximum tolerated dose (MTD) is reached. 3 participants will be in each cohort beginning with the lowest possible dose of 3Gy to a maximum dose of 12Gy. All Cause Mortality Total 0/2 0% Serious Adverse Events Total 0/2 0% Adverse Events not including serious adverse events Total 2/2 100% Oral Mucositis 2/2 100% Diarrhea 2/2 100% Nausea 1/2 50% Non-productive cough 1/2 50% Rash to face and back 1/2 50% Throat pain 1/2 50% GI bleed 1/2 50%
All Cause Mortality
	Cohort 1 TMI Dose 3Gy
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Serious Adverse Events
	Cohort 1 TMI Dose 3Gy
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1 TMI Dose 3Gy
	Affected / at Risk (%)	# Events
Total	2/2 (100%)
Gastrointestinal disorders
Diarrhea	2/2 (100%)	2
GI bleed	1/2 (50%)	1
Nausea	1/2 (50%)	1
General disorders
Mucositis	2/2 (100%)	2
Throat pain	1/2 (50%)	1
Respiratory, thoracic and mediastinal disorders
Non-productive cough	1/2 (50%)	1
Shortness of breath on exertion	1/2 (50%)	1
Skin and subcutaneous tissue disorders
Rash to face and back	1/2 (50%)	1

Limitations/Caveats

Only 2 subjects received total marrow irradiation at 3Gy dose

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.