Allogeneic Transplantation From Related Haploidentical Donors

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00185692
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arm: 1
• Duration (Months): 124
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the feasibility and safety of transplanting CD34+ selected hematopoietic cells from a haploidentical related donor following a nonmyeloablative regimen of total lymphoid irradiation (TLI) and antithymocyte globulin (ATG).

Condition or Disease	Intervention/Treatment	Phase
Blood Cancer; Leukemia; Graft Versus Host Disease; Malignancy; CLL; NHL; Hodgkin's Disease; MDS	Procedure: non-myeloablative hematopoietic cell transplantation; Drug: Anti-Thymocyte Globulin; Drug: Cyclosporine; Drug: Mycophenolate Mofetil; Drug: G-CSF; Drug: Solumedrol; Drug: Acetaminophen; Drug: Diphenydramine; Drug: Hydrocortisone	Phase 2

Detailed Description

An alternative to conventional allogeneic bone marrow transplantation is by using a non-myeloablative conditioning regimen. This regime would consist of both; total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG). Used in combination to achieve engraftment of haploidentical CD34+ selected peripheral blood stem cells in older patients or patients with underlying medical conditions that preclude standard allogeneic treatment. The expected results of this transplant regime will be expected to result in hematopoietic and immunologic reconstitution, decreased deaths related to the treatment regimen and decreased gravft-vs-host disease (GVHD).

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Allogeneic Hematopoietic Cell Transplantation of Positively Selected CD34+ Cells and Defined Inoculum of T Cells From Related Haploidentical Donors for Older Patients With Indolent Hematologic Malignancies
• Study Start Date: Aug 1, 2000
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Dec 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Transplantation of CD34+ cells Week #1: Total Lymphoid Inrradiation (TLI) 120 cGy + Anti-thymocyte Globulin (ATG) 1.5 mg/kg + Solumedrol 1.0 mg/kg Daily for 5 days. Week #2: TLI 120 cGy (3 days a week, double on the 4th day) 5 days of CSP (oraly) one day after TLI was started. 3 days of MMF 4 days after TLI was started.

Procedure: non-myeloablative hematopoietic cell transplantation; TLI and ATG infusion of the donor graft Post-transplant immunosuppression with cyclosporine and mycophenolate mofetil.; Other Names: Peripheral-blood stem-cell transplantation ; Drug: Anti-Thymocyte Globulin; 1.5 mg/kg QD x 5, IV. Dosage will be based on body weight. Purified, sterile IgG fraction of immune serum of rabbits immumixied with human thymus lymphocyte. This drug acts to modify the number and function of lymphocytes.; Other Names: ATG ; Drug: Cyclosporine; 6.25 mg/kg BID, PO.Mechanism of action is inhibition of T-cell activation by binding to a cytoplasmic protein (cyclophillin).; Other Names: INN/BAN USAN CSA ; Drug: Mycophenolate Mofetil; 15 mg/kg Q 8 hours, PO. Inhibtis the enzme inosine monophsophate dehydrogenase (MPDII) noncompetitively which blocks the de nobo synthesis of guanosine required for DNA synthesis and has an effect on T and B cells.; Other Names: MMF CellCept ; Drug: G-CSF; 16 mg/kg, SQ Growth factor used to make bone marrow produce more blood cells; Other Names: Granulocyte colony-stimulating factor CSF 3 ; Drug: Solumedrol; 1.0 mg/kg IV 2 hours prior to ATG Used to treat severe inflamation; Other Names: 6-Methylprednisolone Methylprednisolone Acetate Methylprednisolone Sodium Succinate ; Drug: Acetaminophen; 650 mg PO, 30 minutes prior to infusion Pain reliever; Other Names: Tylenol ; Drug: Diphenydramine; 50 mg IV, 30 minutes prior to infusion Used to relieve allergy symptoms; Other Names: Benadryl Allermax Q-Dryl Diphen Cough ; Drug: Hydrocortisone; 100 mg IV, 1 hour prior to infusion Used to relieve itching, redness and swelling of the skin; Other Names: Hydrocortisone Sodium Phosphate

Outcome Measures

Primary Outcome Measures

1. Engraftment of Haploidentical CD34+ Selected Blood Stem Cells in Older Patients or Those With Medical Co-morbidities Following Total Lymphoid Irradiation and Antithymocyte Globulin Transplant Conditioning [100 days]

   number achieving donor cell engraftment (>95%) by day 90 after transplant.

Secondary Outcome Measures

1. Acute Graft-versus-Host Disease (GVHD) Grade 2-4 Risk From Time of Transplant Until Day 90 Post-transplant [90 days]

   GVHD grading system goes from 0-4 where grade 4 is the most severe. Grade 0 and 1 do not require systemic treatment, Grade 2-4 require treatment. This trial evaluated the risk of developing acute GVHD grades 2-4 within 90 days of transplant.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Months and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age ≥ 50 years with hematologic malignancies treatable by a mixed chimera allogeneic HCT.

• For patients ≤ 50 years of age with hematologic malignacies treatable with mixed chimera HCT who because of pre-exisiting medical conditions or prior therapy are considered to be at high risk for regimen-related toxicity associated with conventional transplants.

• Indolent advanced stage NHL, CLL, HD - Must have received and failed front-line therapy.

• Multiple myeloma (Stage II or III) - Must have received prior chemotherapy. Consolidation after prior autografting is permitted.

• AML/ALL - Must be in complete hematologic remission and have received cytotoxic chemotherapy at some stage before transplant. Patients with molecular or cytogenetic relapse will be accepted providing a donor is available. Patients with persistent or refractory disease will be considered on a case by case basis and transplants must be approved by the principal investigator.

• CML - Patients will be accepted in chronic or accelerated phase. Patients who have received prior autografts after high dose therapy or have undergone intensive chemotherapy for either peripheral blood stem cell mobilization or treatment of advanced CML may be enrolled provided they are in CR, chronic phase or accelerated phase.

• MDS - All patients with MDS will be eligible for this protocol, however, those patients with >10% blasts will require chemotherapy to reduce the blast % to < 10%.

• SAA - Patients with severe aplastic anemia who have failed front line therapy.

• A fully HLA-identical sibling donor is not available.

• A matched unrelated donor has not been identified.

• A haploidentical related donor is available who is in good health and does not have contraindications to donation.

Exclusion Criteria:

• Patients with rapidly progressive intermediate or high grade NHL

• Uncontrolled CNS involvement with disease

• Fertile men

• Women unwilling to use contraceptive techniques during and for 12 months following treatment

• Females who are pregnant

• Cardiac function: ejection fraction < 30% or cardiac failure requiring therapy

• Pulmonary: DLCO < 40% predicted and/or receiving supplementary continuous oxygen

• Liver function abnormalities: elevation of bilirubin to > 4 mg/dl and/or transaminases

3x the upper limit of normal. If hyperbilirubinemai is due to a known cause that will not increase the risks of transplant, than this upper limit may be exceeded.

• Renal: creatinine clearance < 50 cc/min (24 hour urine collection)

• Karnofsky performance score < 60%

• Patients with poorly controlled hypertension.

• Documented fungal disease that persists despite treatment

• HIV positive patients.

• Hepatitis B and C positive patients will be evaluated on a case by case basis

• Psychiatric disorders or psychosocial problems which in the opinion of the primary physician or principal investigator would place the patient at unacceptable risk from this regimen.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Robert Lowsky, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Robert Lowsky, Associate Professor of Medicine, Stanford University
• ClinicalTrials.gov Identifier: NCT00185692
• Other Study ID Numbers: IRB-13371; 75117; BMT124
• First Posted: Sep 16, 2005
• Last Update Posted: Dec 4, 2019
• Last Verified: Jan 1, 2015

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Neoplasms; Hodgkin Disease; Hematologic Neoplasms; Graft vs Host Disease; Acetaminophen; Cyclosporine; Mycophenolic Acid; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Cyclosporins; Antilymphocyte Serum; Lenograstim; Prednisolone hemisuccinate; Prednisolone phosphate

Study Results

Participant Flow

Arm/Group Title	Transplating of CD34+ Selected Hematopietic Cells
Arm/Group Description
Period Title: Overall Study
STARTED	16
COMPLETED	0
NOT COMPLETED	16

Baseline Characteristics

Arm/Group Title	Transplating of CD34+ Selected Hematopietic Cells
Arm/Group Description
Overall Participants	16
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	52
Sex: Female, Male (Count of Participants)
Female	6 37.5%
Male	10 62.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 25%
Not Hispanic or Latino	12 75%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 6.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	14 87.5%
More than one race	1 6.3%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Engraftment of Haploidentical CD34+ Selected Blood Stem Cells in Older Patients or Those With Medical Co-morbidities Following Total Lymphoid Irradiation and Antithymocyte Globulin Transplant Conditioning
Description	number achieving donor cell engraftment (>95%) by day 90 after transplant.
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transplantation of CD34+ Cells
Arm/Group Description	Week #1: Total Lymphoid Inrradiation (TLI) 120 cGy + Anti-thymocyte Globulin (ATG) 1.5 mg/kg + Solumedrol 1.0 mg/kg Daily for 5 days. Week #2: TLI 120 cGy (3 days a week, double on the 4th day) 5 days of CSP (oraly) one day after TLI was started. 3 days of MMF 4 days after TLI was started. non-myeloablative hematopoietic cell transplantation: TLI and ATG infusion of the donor graft Post-transplant immunosuppression with cyclosporine and mycophenolate mofetil. Anti-Thymocyte Globulin: 1.5 mg/kg QD x 5, IV. Dosage will be based on body weight. Purified, sterile IgG fraction of immune serum of rabbits immumixied with human thymus lymphocyte. This drug acts to modify the number and function of lymphocytes. Cyclosporine: 6.25 mg/kg BID, PO.Mechanism of action is inhibition of T-cell activation by binding to a cytoplasmic protein (cyclophillin). Mycophenolate Mofetil: 15 mg/kg Q 8 hours, PO. Inhibtis the enzme inosine monophsophate dehydrogenase (MPDII) noncompetitively
Measure Participants	16
Count of Participants [Participants]	4 25%

2. Secondary Outcome

Title	Acute Graft-versus-Host Disease (GVHD) Grade 2-4 Risk From Time of Transplant Until Day 90 Post-transplant
Description	GVHD grading system goes from 0-4 where grade 4 is the most severe. Grade 0 and 1 do not require systemic treatment, Grade 2-4 require treatment. This trial evaluated the risk of developing acute GVHD grades 2-4 within 90 days of transplant.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transplantation of CD34+ Cells
Arm/Group Description	Week #1: Total Lymphoid Inrradiation (TLI) 120 cGy + Anti-thymocyte Globulin (ATG) 1.5 mg/kg + Solumedrol 1.0 mg/kg Daily for 5 days. Week #2: TLI 120 cGy (3 days a week, double on the 4th day) 5 days of CSP (oraly) one day after TLI was started. 3 days of MMF 4 days after TLI was started. non-myeloablative hematopoietic cell transplantation: TLI and ATG infusion of the donor graft Post-transplant immunosuppression with cyclosporine and mycophenolate mofetil. Anti-Thymocyte Globulin: 1.5 mg/kg QD x 5, IV. Dosage will be based on body weight. Purified, sterile IgG fraction of immune serum of rabbits immumixied with human thymus lymphocyte. This drug acts to modify the number and function of lymphocytes. Cyclosporine: 6.25 mg/kg BID, PO.Mechanism of action is inhibition of T-cell activation by binding to a cytoplasmic protein (cyclophillin). Mycophenolate Mofetil: 15 mg/kg Q 8 hours, PO. Inhibtis the enzme inosine monophsophate dehydrogenase (MPDII) noncompetitively
Measure Participants	16
Count of Participants [Participants]	1 6.3%

Adverse Events

Time Frame	120 days
Adverse Event Reporting Description	Non-serious adverse events were not collected.
Arm/Group Title	CD34+ Selected Hematopietic Cells
Arm/Group Description
All Cause Mortality
	CD34+ Selected Hematopietic Cells
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	CD34+ Selected Hematopietic Cells
	Affected / at Risk (%)	# Events
Total	14/16 (87.5%)
General disorders
Death	14/16 (87.5%)	14
Other (Not Including Serious) Adverse Events
	CD34+ Selected Hematopietic Cells
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

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.