Mini-Allogeneic Peripheral Blood Progenitor Cell Transplantation For Recurrent or Metastatic Breast Cancer

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00429572
• Collaborator: (none)
• Enrollment: 19
• Location: 1
• Arm: 1
• Duration (Months): 124
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Primary Objectives:

1. To assess the feasibility of mini-allogeneic Peripheral Blood Progenitor Cell (PBPC) transplantation in patients with recurrent or metastatic breast cancer.

2. To determine the success rate (complete remission without severe toxicity or death) at 100 days after the transplant and long-term progression free survival (PFS) rate.

3. To examine the graft vs. breast cancer effect of allogeneic PBPC transplantation.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Fludarabine; Drug: Melphalan; Procedure: Stem Cell Infusion	Phase 2

Detailed Description

If tumors shrink by standard-dose chemotherapy, patients will receive moderate dose chemotherapy to prepare for the blood stem cell transplant. The drug fludarabine will be given by vein on days 1-5. The drug melphalan will be given by vein on days 4 and 5. Day 6 will be a rest day; no drugs will be given. The blood stem cell transplant will be given on day 7. Bone marrow from the matched donor may be used instead of blood stem cells, particularly for unrelated donors. A catheter (tube) will be placed in a large vein in the chest to reduce the number of times patients are stuck with a needle.

Researchers will collect blood stem cells from your brother or sister or from an unrelated donor using granulocyte colony-stimulating factor (G-CSF) before receiving high-dose chemotherapy. You will need to have enough stem cells before transplantation.

The drugs G-CSG, tacrolimus, and methotrexate will be given to ease side effects and help blood counts return to normal after the transplant. G-CSF is given as a shot under the skin, starting the day from transplant and continuing until the white blood cell count is normal. Tacrolimus is given by vein or by mouth for 4 to 7 months; during the last month it is given, the dose will be tapered off. Methotrexate is given by vein on days 1, 3, and 6 after transplant. Day 11 of methotrexate is given additionally if a donor is unrelated. Blood transfusions may be needed also.

Antithymocyte globulin will be given to patients who receive blood or bone marrow from donors whose cells do exactly match the patients or from unrelated donors.

Sometimes the transplanted cells attack the normal cells in the patient's body instead of the cancer cells. This is called graft-vs-host disease (GVHD). The drug methylprednisolone will be given by vein or by mouth to fight GVHD is it occurs.

Patients must stay in the hospital for about 3 to 4 weeks. Patients must stay in the Houston area for about 100 days after the transplant. Blood tests will be done daily while the patient is in the hospital. Blood and urine tests and chest x-rays, computer tomography (CT) scans, and/or bone scans will be done during the 100 days.

If there are no signs of disease after 100 days, treatment will stop. Patients must return to the clinic for check-ups once a month for the first year, 3 times a year for 4 years, and once a year after that. If disease is till present after 100 days, but the patient does not have GVHD, the patient may receive an infusion of donor lymphocytes by vein. This treatment may be repeated up to 3 times with 8 weeks between infusions. If no disease is found or if GVHD occurs, treatment will stop.

Before treatment starts, patients will have a complete exam including blood and urine tests. An EKG (heart function test) and a heart scan will be done. Patients will have a dental exam. A test of lung function will be done. A sample of breast tissue will be taken. This is done with a hollow needle while the doctor looks at a CT scan or with a lighted tube placed through a cut in the breast while the patient is under anesthesia.

Herceptin will be given every week, if you have Human Epidermal growth factor Receptor 2 (HER-2)/neu-overexpressing tumor. Prior to this an infusion heart test will be done.

This is an investigational study. Docetaxel, Melphalan, and Herceptin are approved by the US Food and Drug Administration for use against breast cancer. About 40 patients will take part in the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Mini-Allogeneic Peripheral Blood Progenitor Cell Transplantation For Recurrent or Metastatic Breast Cancer
• Study Start Date: Jan 1, 1998
• Actual Primary Completion Date: May 1, 2008
• Actual Study Completion Date: May 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Allogeneic Transplantation Intravenous Fludarabine 30 mg/m^2 daily on days 1-5, and Melphalan 70 mg/m^2 on days 4 and 5 followed by blood stem cell transplant on day 7.	Drug: Fludarabine; 30 mg/m^2 intravenously Daily for 5 Days; Drug: Melphalan; 70 mg/m^2 intravenously Daily for 2 Days; Procedure: Stem Cell Infusion; Stem Cell Infusion on Day 0.; Other Names: mini-allogeneic PBPC transplantation Stem Cell Transplant SCT

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Tumor Response [Baseline to measured progressive disease (post study follow-up period 24 months starting from the date of the last drug administration). Data collected every 4 months.]

   Best response recorded from start of treatment until disease progression/recurrence using World Health Organization (WHO) criteria of Complete Response: disappearance of all disease/symptoms > 4 weeks; Partial response, > 50% reduction in sum of products of diameters of each measurable lesion for more than 4 weeks; Stable Disease, no change in tumor size; and Progressive Disease, appearance of new lesions or > 25% increase in sum of products of diameters of any measurable lesions.

2. Overall Survival [Transplant until death.]

   Survival duration was calculated from time of transplantation by number of days.

3. Time to Progressive Disease [Transplant to Progression.]

   Progression-free was measured, by days, at time from transplantation to development to disease or death from any cause, which ever occurred first.

4. Grade II-IV Toxicity [Up to one year.]

   Non-hematopoietic toxicity within the first year of transplantation, acute Graft versus Host Disease (GVHD) above National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade I and chronic above Grade I are reported by participant incidence. Broad classification of adverse events (AE) categories based on anatomy and/or pathophysiology; within each category, AEs are listed accompanied by their descriptions of severity (Grade, Grade 1 least severe).

5. Number of Participants With Acute or Chronic GVHD And Response to Therapy [Transplant to 1 year post transplant]

   Participants diagnosed with Graft versus Host Disease (GVHD) post transplant were divided into either acute (aGVHD), normally observed within the first 100 days post-transplant; and chronic GVHD (cGVHD) cases, normally occur after 100 days, then evaluated and scored according to standard criteria from "Consensus conference on acute GVHD grading," Bone Marrow Transplant 1995; 15: 825-828, noted is type of case and whether responds to therapy.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Recurrent or residual metastatic breast carcinoma

• Zubrod performance status less than 2

• 18-60 years old

• Related donor human leukocyte antigen (HLA)-compatible for allogeneic transplantation or unrelated HLA-compatible donor.

• No major organ dysfunction or active infection

Exclusion Criteria: None

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	U.T.M.D. Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center

Investigators

• Principal Investigator: Naoto Ueno, MD, PhD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• The University of Texas M.D.Anderson Cancer Center

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00429572
• Other Study ID Numbers: DM97-268
• First Posted: Jan 31, 2007
• Last Update Posted: Aug 7, 2012
• Last Verified: Aug 1, 2012

• Keywords provided by M.D. Anderson Cancer Center: Breast Cancer; PBPC Transplantation; Stem Cell Infusion; Fludarabine; Melphalan
• Additional relevant MeSH terms: Breast Neoplasms; Fludarabine; Melphalan

Study Results

Participant Flow

Recruitment Details	Recruitment Period of January 1999 to December 2006. All participants were recruited at University of Texas MD Anderson Cancer Center.

Arm/Group Title	Allogeneic Transplantation
Arm/Group Description	Intravenous Fludarabine 30 mg/m^2 daily on days 1-5, and Melphalan 70 mg/m^2 on days 4 and 5 followed by blood stem cell transplant on day 7.
Period Title: Overall Study
STARTED	19
COMPLETED	18
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Allogeneic Transplantation
Arm/Group Description	Intravenous Fludarabine 30 mg/m^2 daily on days 1-5, and Melphalan 70 mg/m^2 on days 4 and 5 followed by blood stem cell transplant on day 7.
Overall Participants	19
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	41
Sex: Female, Male (Count of Participants)
Female	19 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	19 100%
Tumor Characteristic (participants) [Number]
ER negative	12 63.2%
ER positive	7 36.8%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Tumor Response
Description	Best response recorded from start of treatment until disease progression/recurrence using World Health Organization (WHO) criteria of Complete Response: disappearance of all disease/symptoms > 4 weeks; Partial response, > 50% reduction in sum of products of diameters of each measurable lesion for more than 4 weeks; Stable Disease, no change in tumor size; and Progressive Disease, appearance of new lesions or > 25% increase in sum of products of diameters of any measurable lesions.
Time Frame	Baseline to measured progressive disease (post study follow-up period 24 months starting from the date of the last drug administration). Data collected every 4 months.

Outcome Measure Data

Analysis Population Description

As treated: Eighteen received the allogeneic transplantation.

Arm/Group Title	Allogeneic Transplantation
Arm/Group Description	Intravenous Fludarabine 30 mg/m^2 daily on days 1-5, and Melphalan 70 mg/m^2 on days 4 and 5 followed by blood stem cell transplant on day 7.
Measure Participants	18
Complete Response	5 26.3%
Stable Disease	9 47.4%
Partial Response	1 5.3%
Progressive Disease	3 15.8%

2. Primary Outcome

Title	Overall Survival
Description	Survival duration was calculated from time of transplantation by number of days.
Time Frame	Transplant until death.

Outcome Measure Data

Analysis Population Description

As treated: Eighteen received the allogeneic transplantation.

Arm/Group Title	Allogeneic Transplantation
Arm/Group Description	Intravenous Fludarabine 30 mg/m^2 daily on days 1-5, and Melphalan 70 mg/m^2 on days 4 and 5 followed by blood stem cell transplant on day 7.
Measure Participants	18
Median (Full Range) [Days]	643

3. Primary Outcome

Title	Time to Progressive Disease
Description	Progression-free was measured, by days, at time from transplantation to development to disease or death from any cause, which ever occurred first.
Time Frame	Transplant to Progression.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allogeneic Transplantation
Arm/Group Description	Intravenous Fludarabine 30 mg/m^2 daily on days 1-5, and Melphalan 70 mg/m^2 on days 4 and 5 followed by blood stem cell transplant on day 7.
Measure Participants	18
Median (Full Range) [Days]	202

4. Primary Outcome

Title	Grade II-IV Toxicity
Description	Non-hematopoietic toxicity within the first year of transplantation, acute Graft versus Host Disease (GVHD) above National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade I and chronic above Grade I are reported by participant incidence. Broad classification of adverse events (AE) categories based on anatomy and/or pathophysiology; within each category, AEs are listed accompanied by their descriptions of severity (Grade, Grade 1 least severe).
Time Frame	Up to one year.

Outcome Measure Data

Analysis Population Description

As treated: Eighteen received the allogeneic transplantation.

Arm/Group Title	Allogeneic Transplantation
Arm/Group Description	Intravenous Fludarabine 30 mg/m^2 daily on days 1-5, and Melphalan 70 mg/m^2 on days 4 and 5 followed by blood stem cell transplant on day 7.
Measure Participants	18
Cardiac	1 5.3%
Pulmonary	3 15.8%
Gastrointestinal	8 42.1%
Renal	0 0%
Neurological	2 10.5%
Fever/Flu like symptoms	2 10.5%
Infection	3 15.8%
Genitourinary	2 10.5%
Skin	2 10.5%

5. Primary Outcome

Title	Number of Participants With Acute or Chronic GVHD And Response to Therapy
Description	Participants diagnosed with Graft versus Host Disease (GVHD) post transplant were divided into either acute (aGVHD), normally observed within the first 100 days post-transplant; and chronic GVHD (cGVHD) cases, normally occur after 100 days, then evaluated and scored according to standard criteria from "Consensus conference on acute GVHD grading," Bone Marrow Transplant 1995; 15: 825-828, noted is type of case and whether responds to therapy.
Time Frame	Transplant to 1 year post transplant

Outcome Measure Data

Analysis Population Description

As treated: Eighteen received the allogeneic transplantation.

Arm/Group Title	Allogeneic Transplantation
Arm/Group Description	Intravenous Fludarabine 30 mg/m^2 daily on days 1-5, and Melphalan 70 mg/m^2 on days 4 and 5 followed by blood stem cell transplant on day 7.
Measure Participants	18
aGVHD	9 47.4%
aGVHD responded to therapy	7 36.8%
cGVHD	14 73.7%
cGVHD responded to therapy	14 73.7%

Adverse Events

Time Frame	7 Years
Adverse Event Reporting Description	Cardiac 1 Pulmonary 3 Gastrointestinal 8 Renal 0 Neurological 2 Fever/Flu like symptoms 2 Infection 3 Genitourinary 2 Skin 2
Arm/Group Title	Allogeneic Transplantation
Arm/Group Description	Intravenous Fludarabine 30 mg/m^2 daily on days 1-5, and Melphalan 70 mg/m^2 on days 4 and 5 followed by blood stem cell transplant on day 7.
All Cause Mortality
	Allogeneic Transplantation
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Allogeneic Transplantation
	Affected / at Risk (%)	# Events
Total	0/19 (0%)
Other (Not Including Serious) Adverse Events
	Allogeneic Transplantation
	Affected / at Risk (%)	# Events
Total	9/19 (47.4%)
Gastrointestinal disorders
Diarhhea	9/19 (47.4%)
Nausea	9/19 (47.4%)
Vomitting	9/19 (47.4%)
Skin and subcutaneous tissue disorders
Skin rash	9/19 (47.4%)

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.