Non-Myeloablative Allogeneic HSCT From HLA Matched Related or Unrelated Donors for the Treatment of Low Grade B Cell Malignancies

• Sponsor: University of Alabama at Birmingham (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00714259
• Collaborator: (none)
• Enrollment: 5
• Location: 1
• Arm: 1
• Duration (Months): 55.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

A non-myeloablative treatment strategy and uniform selection criteria will enable patients with a variety of low grade B-Cell malignancies to attain long term disease control without unacceptably high treatment related mortality.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma; CLL / SLL; Non Hodgkin's Lymphoma; Waldenstroms; Mantle Cell Lymphoma	Drug: Fludarabine; Radiation: Total Body Irradiation; Other: Infusion of Stem Cells	Phase 2/Phase 3

Detailed Description

Non myeloablative transplant aims to achieve the immunological advantage of graft versus tumor effect as conventional myeloablative therapy without causing high treatment related toxicities. Non myeloablative transplant has been gaining wider acceptance as a way to achieve longer disease free and over all survival in patients with low grade B-cell malignancies, which otherwise is an incurable disease. Recent studies of non-myeloablative HSCT have demonstrated the powerful effect of graft versus leukemia alone against myeloma and other malignant B-cell malignancies if the transplant is performed for low grade, low volume disease.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: UAB 0775 Phase II Trial of Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation Protocol From HLA Matched Related Donors for The Treatment of Patients With Low Grade B Cell Malignancies
• Study Start Date: Jul 1, 2008
• Actual Primary Completion Date: Feb 1, 2013
• Actual Study Completion Date: Feb 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Other: Non Myeloablative Treatment Non-myeloablative Transplant Conditioning Chemotherapy : Fludarabine - 30 mg/m2/day x 3 days Total Body Irradiation - 200cGy x1 dose Infusion of Stem Cells - On Day 0 pts will received an infusion of HLA matched sibling donor stem cells. Dose is determined by the volume of cells obtained from donor. Minimum dose is 2x10*6 CD34+ cells per kilogram of recipient weight.

Drug: Fludarabine; Fludarabine 30 mg/m2/day x 3 days; Radiation: Total Body Irradiation; TBI 200cGy x1 dose on transplant day; Other: Infusion of Stem Cells; On Day 0 pts will received an infusion of HLA matched sibling donor stem cells. Dose is determined by the volume of cells obtained from donor. Minimum dose is 2x10*6 CD34+ cells per kilogram of recipient weight.

Outcome Measures

Primary Outcome Measures

1. Progressive Free Survival Post Transplant [100 days post transplant]

   subjects surviving without disease progression at 100 days after transplant as evidenced by decreased disease and no new disease showing on radiologic scans and / or bone marrow pathology.

2. Progressive Free Survival Post Transplant [180 days post transplant]

   Subjects surviving without disease progression 180 days after transplant as evidenced by decreased disease and no new disease showing on radiologic scans and / or bone marrow pathology.

3. Progressive Free Survival Post Transplant [365 days post transplant]

   Subjects surviving without disease progression 365 days after transplant as evidenced by decreased disease and no new disease showing on radiologic scans and / or bone marrow pathology.

4. Progression Free Survival Post Transplant [2 years post transplant]

   Subjects surviving without disease progression 2 years after transplant as evidenced by no new disease showing on radiologic scans and / or bone marrow pathology.

Secondary Outcome Measures

1. Non-relapse Treatment Related Mortality [Within 100 days post transplant]

   Death related to treatment without relapse within 100 days after transplant

2. Number of Participants With Detectable Donor Chimerism at up to 100 Days Post Transplant [Post transplant up to 100 days post transplant]

   Measured by number of participants that have chimerism study results that show the number of donor cells and the number of recipient cells present in the blood after post-transplant lymphocyte infusions continue to be predominately either donor or recipient.

3. Composite Incidence of Acute and Chronic Graft Versus Host Disease [Up to 100 days post transplant.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Stage II or III non-progressive disease Multiple Myeloma.

• CLL/SLL, and low grade Hodgkin Lymphomas that are in a very good partial response or complete response with non-progressive disease.

• ≤ 70 years old.

• Eligible and willing HLA matched related donor.

• Bilirubin <2xULN.

• ALT and AST <3xULN.

• LVEF > 40%.

• Creatinine Clearance >40mL/min.

• Pulmonary function DLCO corrected to ≥ 70%.

• Minimum performance score of 70%.

• Platelet count >130 x103 micro L.

• LDH ≤1.5xULN.

• No proceeding co-morbid condition that significantly increases the risk of severe regimen related toxicity.

• No uncontrolled infections.

Exclusion Criteria:

• Age >70 years old.

• Performance status <70%.

• Uncontrolled infections or is HIV positive

• Prior malignancies that are felt to have a <80% probability of being cured.

• Pregnant, breastfeeding, or refuse to use contraceptive techniques during and for 12 months following transplant.

• Prior Allograft

• History of rapidly growing disease at diagnosis or at any progression or have MDS.

• No eligible and willing HLA matched donor.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama in Birmingham BMT/CT Program Outpatient Clinic	Birmingham	Alabama	United States	35249-6979

Sponsors and Collaborators

• University of Alabama at Birmingham

Investigators

• Principal Investigator: William P. Vaughan, MD, University of Alabama in Birmingham

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Racquel Innis-Shelton, MD, Principal Investigator, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT00714259
• Other Study ID Numbers: F080429003; UAB-0775
• First Posted: Jul 14, 2008
• Last Update Posted: Jul 24, 2017
• Last Verified: Jun 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Racquel Innis-Shelton, MD, Principal Investigator, University of Alabama at Birmingham: Low Grade B Cell Malignancies; nonmyeloablative transplant; allogeneic
• Additional relevant MeSH terms: Lymphoma; Multiple Myeloma; Neoplasms; Lymphoma, Mantle-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Fludarabine

Study Results

Participant Flow

Arm/Group Title	Single Arm Trial
Arm/Group Description	Single Arm Intervention trial as noted in interventions section Fludarabine: Fludarabine 30 mg/m2/day x 3 days Total Body Irradiation: TBI 200cGy x1 dose on transplant day Infusion of Stem Cells: On Day 0 pts will received an infusion of HLA matched sibling donor stem cells. Dose is determined by the volume of cells obtained from donor. Minimum dose is 2x10*6 CD34+ cells per kilogram of recipient weight.
Period Title: Overall Study
STARTED	5
COMPLETED	3
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Single Arm Trial
Arm/Group Description	Single Arm Intervention trial as noted in interventions section Fludarabine: Fludarabine 30 mg/m2/day x 3 days Total Body Irradiation: TBI 200cGy x1 dose on transplant day Infusion of Stem Cells: On Day 0 pts will received an infusion of HLA matched sibling donor stem cells. Dose is determined by the volume of cells obtained from donor. Minimum dose is 2x10*6 CD34+ cells per kilogram of recipient weight.
Overall Participants	5
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	5 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	1 20%
Male	4 80%

Outcome Measures

1. Primary Outcome

Title	Progressive Free Survival Post Transplant
Description	subjects surviving without disease progression at 100 days after transplant as evidenced by decreased disease and no new disease showing on radiologic scans and / or bone marrow pathology.
Time Frame	100 days post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm Trial
Arm/Group Description	Single Arm Intervention trial as noted in interventions section Fludarabine: Fludarabine 30 mg/m2/day x 3 days Total Body Irradiation: TBI 200cGy x1 dose on transplant day Infusion of Stem Cells: On Day 0 pts will received an infusion of HLA matched sibling donor stem cells. Dose is determined by the volume of cells obtained from donor. Minimum dose is 2x10*6 CD34+ cells per kilogram of recipient weight.
Measure Participants	5
Number [participants]	4 80%

2. Secondary Outcome

Title	Non-relapse Treatment Related Mortality
Description	Death related to treatment without relapse within 100 days after transplant
Time Frame	Within 100 days post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm Trial
Arm/Group Description	Single Arm Intervention trial as noted in interventions section Fludarabine: Fludarabine 30 mg/m2/day x 3 days Total Body Irradiation: TBI 200cGy x1 dose on transplant day Infusion of Stem Cells: On Day 0 pts will received an infusion of HLA matched sibling donor stem cells. Dose is determined by the volume of cells obtained from donor. Minimum dose is 2x10*6 CD34+ cells per kilogram of recipient weight.
Measure Participants	5
Number [participants]	0 0%

3. Secondary Outcome

Title	Number of Participants With Detectable Donor Chimerism at up to 100 Days Post Transplant
Description	Measured by number of participants that have chimerism study results that show the number of donor cells and the number of recipient cells present in the blood after post-transplant lymphocyte infusions continue to be predominately either donor or recipient.
Time Frame	Post transplant up to 100 days post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm Trial
Arm/Group Description	Single Arm Intervention trial as noted in interventions section Fludarabine: Fludarabine 30 mg/m2/day x 3 days Total Body Irradiation: TBI 200cGy x1 dose on transplant day Infusion of Stem Cells: On Day 0 pts will received an infusion of HLA matched sibling donor stem cells. Dose is determined by the volume of cells obtained from donor. Minimum dose is 2x10*6 CD34+ cells per kilogram of recipient weight.
Measure Participants	5
Number [participant]	1

4. Secondary Outcome

Title	Composite Incidence of Acute and Chronic Graft Versus Host Disease
Time Frame	Up to 100 days post transplant.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm Trial
Arm/Group Description	Single Arm Intervention trial as noted in interventions section Fludarabine: Fludarabine 30 mg/m2/day x 3 days Total Body Irradiation: TBI 200cGy x1 dose on transplant day Infusion of Stem Cells: On Day 0 pts will received an infusion of HLA matched sibling donor stem cells. Dose is determined by the volume of cells obtained from donor. Minimum dose is 2x10*6 CD34+ cells per kilogram of recipient weight.
Measure Participants	5
Number [participants]	2 40%

5. Primary Outcome

Title	Progressive Free Survival Post Transplant
Description	Subjects surviving without disease progression 180 days after transplant as evidenced by decreased disease and no new disease showing on radiologic scans and / or bone marrow pathology.
Time Frame	180 days post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm Trial
Arm/Group Description	Single Arm Intervention trial as noted in interventions section Fludarabine: Fludarabine 30 mg/m2/day x 3 days Total Body Irradiation: TBI 200cGy x1 dose on transplant day Infusion of Stem Cells: On Day 0 pts will received an infusion of HLA matched sibling donor stem cells. Dose is determined by the volume of cells obtained from donor. Minimum dose is 2x10*6 CD34+ cells per kilogram of recipient weight.
Measure Participants	4
Number [participants]	4 80%

6. Primary Outcome

Title	Progressive Free Survival Post Transplant
Description	Subjects surviving without disease progression 365 days after transplant as evidenced by decreased disease and no new disease showing on radiologic scans and / or bone marrow pathology.
Time Frame	365 days post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm Trial
Arm/Group Description	Single Arm Intervention trial as noted in interventions section Fludarabine: Fludarabine 30 mg/m2/day x 3 days Total Body Irradiation: TBI 200cGy x1 dose on transplant day Infusion of Stem Cells: On Day 0 pts will received an infusion of HLA matched sibling donor stem cells. Dose is determined by the volume of cells obtained from donor. Minimum dose is 2x10*6 CD34+ cells per kilogram of recipient weight.
Measure Participants	4
Number [participants]	4 80%

7. Primary Outcome

Title	Progression Free Survival Post Transplant
Description	Subjects surviving without disease progression 2 years after transplant as evidenced by no new disease showing on radiologic scans and / or bone marrow pathology.
Time Frame	2 years post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm Trial
Arm/Group Description	Single Arm Intervention trial as noted in interventions section Fludarabine: Fludarabine 30 mg/m2/day x 3 days Total Body Irradiation: TBI 200cGy x1 dose on transplant day Infusion of Stem Cells: On Day 0 pts will received an infusion of HLA matched sibling donor stem cells. Dose is determined by the volume of cells obtained from donor. Minimum dose is 2x10*6 CD34+ cells per kilogram of recipient weight.
Measure Participants	4
Number [participants]	2 40%

Adverse Events

Arm/Group Title	Single Arm Trial
Arm/Group Description	Single Arm Intervention trial as noted in interventions section Fludarabine: Fludarabine 30 mg/m2/day x 3 days Total Body Irradiation: TBI 200cGy x1 dose on transplant day Infusion of Stem Cells: On Day 0 pts will received an infusion of HLA matched sibling donor stem cells. Dose is determined by the volume of cells obtained from donor. Minimum dose is 2x10*6 CD34+ cells per kilogram of recipient weight.
All Cause Mortality
	Single Arm Trial
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Single Arm Trial
	Affected / at Risk (%)	# Events
Total	3/5 (60%)
Respiratory, thoracic and mediastinal disorders
RSV pneumonia Infection	1/5 (20%)	1
Klebsiella pneumonia Infection	1/5 (20%)	1
Pneumonia	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	Single Arm Trial
	Affected / at Risk (%)	# Events
Total	0/5 (0%)

Limitations/Caveats

[Not Specified]

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.