Haplo/Cord: Hematopoietic Stem Cell Transplantation (HSCT) Using CD34 Selected Mismatched Related Donor and One Umbilical Cord Unit

• Sponsor: Medical College of Wisconsin (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01050946
• Collaborator: (none)
• Enrollment: 1
• Arm: 1
• Duration (Months): 44

Study Details

Study Description

Brief Summary

This study is a means of providing transplantation to those patients who would be a stem cell transplant candidate who do not have an appropriate donor.

The use of CD34 selected haploidentical donor with an umbilical cord unit may help provide earlier engraftment without the need for long term immunosuppression.

This study tests a new method of bone marrow transplantation called combined haploidentical-cord blood transplantation. In this procedure, some of the blood forming cells (the stem cells) from a partially human leukocyte antigen (HLA) matched (haploidentical) related donor are collected from the blood, as well as cells from an umbilical cord are transplanted into the patient (the recipient) after administration of a "conditioning regimen". A conditioning regimen consists of chemotherapy and sometimes radiation to the entire body (total body irradiation, or TBI), which is meant to destroy the cancer cells and suppress the recipient's immune system to allow the transplanted cells to take (grow).

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Lymphocytic, Acute; Leukemia, Lymphocytic, Chronic; Leukemia, Myelocytic, Acute; Leukemia, Myeloid, Chronic; Lymphoma, Non-Hodgkin; Lymphoma, Hodgkins	Biological: Haploidentical/cord transplant	Phase 2

Detailed Description

This method of stem cell transplantation is designed to overcome some of the limitations of other alternative donor transplant options. Use of unrelated umbilical cord unit (UCB) donors appears to allow a greater degree of HLA mismatch with acceptable rates of GVHD. However, when UCB transplant was studied in the adult population, investigators discovered several limitations. One major limitation with UCB was delayed engraftment, resulting in higher risk of infection in the early post transplant period. The limitations to cord blood transplant involve delayed engraftment resulting in early complications such as infections. The main limitation associated with haploidentical donors is the significant immunosuppression required to prevent/treat aGVHD. Use of this combined modality of transplantation appears to allow for rapid neutrophil engraftment from the haploidentical donor and coupled with long term hematopoiesis from the UCB donor, thus requiring less long term immunosuppression.

This study tests a new method of bone marrow transplantation called combined haploidentical-cord blood transplantation. In this procedure, some of the blood forming cells (the stem cells) from a partially HLA matched (haploidentical) related donor are collected from the blood, as well as cells from an umbilical cord are transplanted into the patient (the recipient) after administration of a "conditioning regimen". A conditioning regimen consists of chemotherapy and sometimes radiation to the entire body (total body irradiation, or TBI),

One of two 'conditioning regimens' which will be determined by the physician.

1. FLUDARABINE, MELPHALAN, ATG

Fludarabine 30mg/m2(Days-7,-6,-5,-4,-3)-,Melphalan 70mg/m2(Day -3,-2), ATG 1.5mg/m2(Day-7,-5,-3,-1)

1. FLUDARABINE, BUSULFAN, 400 CGY TBI, ATG Fludarabine 50mg/m2(Day -6,-5,-4,-3,-2),Busulfan 3.2mg/kg(Day -5,-4,-3,-2) 400cGY Total Body Irradiation(TBI)Day-1,ATG 1.5mg/kg(Day-7,-5,-3,-1)

Day 0 -Haploidentical donor and one umbilical cord blood unit infusion

Filgrastim will be administered daily from day +1 until blood counts have completely recovered. Tacrolimus and another immunosuppressant, Cellcept, starting before transplant also to reduce the risks of graft versus host disease and to promote the growth of the graft. Tacrolimus will be given daily from two days before the transplant until at least three months after transplantation. Cellcept, will be tapered after the cells engraft.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study: HSCT Using CD34 Selected Mismatched Related Donor and One Umbilical Cord Unit
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Other: Haploidentical/cord transplant Haploidentical/cord transplant with the precondition regimen at discretion of treating physician.

Biological: Haploidentical/cord transplant; Myeloablative preparative regimen of chemotherapy and radiation followed by mismatch related(haploidentical)donor and one unit umbilical cord blood transplantation. Conditioning Regimens Choice of regimen at the discretion of the treating physician Fludarabine 30mg/m2(Days-7,-6,-5,-4,-3)-,Melphalan 70mg/m2(Day -3,-2), ATG 1.5mg/m2(Day-7,-5,-3,-1) Fludarabine 50mg/m2(Day -6,-5,-4,-3,-2),Busulfan 3.2mg/kg(Day -5,-4,-3,-2),400cGY Total Body Irradiation(TBI)Day-1,ATG 1.5mg/kg(Day-7,-5,-3,-1) Day 0 -Haploidentical donor and one umbilical cord blood unit infusion; Other Names: Cord Blood Transplant

Outcome Measures

Primary Outcome Measures

1. The Primary Objective is to Estimate the Overall Survival, Separately in the Two Risk Strata. [3 years]

Secondary Outcome Measures

1. Time to Relapse: To Assess the Incidence of Acute Leukemia or Lymphoma Relapse From Day of Transplant [2 years]

   NOT analyzed since there was only patient and no relapse was observed till patient passed away

2. Time to Neutrophil Engraftment: To Assess the Incidence of Neutrophil Engraftment From Day of Transplant [100 days]

   time to neutrophil recovery after transplant

3. Time to Platelet Engraftment: To Assess the Incidence of Platelet Engraftment From Day of Transplant, [100 days]

4. Time to Acute GVHD: We Will Assess the Incidence and Severity of Grades II-IV and Grades III-IV Acute GVHD From Day of Transplant. [100 days]

5. Transplant Related Mortality (TRM): TRM is Death Occurring in Patients in Continuous Complete Remission. [1 year]

6. Disease-free Survival:Death or Relapse Will be Considered Events for This Endpoint. [3 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients between 18 and 65 years old

• Patient has a related family member(haploidentical) or unrelated which is 5 of 10 HLA identical match.

Standard Risk

• Acute myelogenous leukemia: CR1 with high risk cytogenetics or molecular abnormalities such as FLT-3 ITD, or CR2 with a first remission that must have lasted > 1 year.

• Acute Lymphocytic Leukemia: CR1, in order to be standard risk must NOT have Philadelphia Chromosome.

• Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): Must be refractory to fludarabine or fail to have a complete or partial response after therapy with a regimen containing fludarabine (or another nucleoside analog, e.g. 2-CDA, pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing fludarabine (or another nucleoside analog).

• Chronic myelogenous leukemia: resistant to or intolerant of TKI, in CP1 or CP2, or with a mutation that suggests resistance to TKI.

• Myelodysplastic Syndrome: RA, RARS, must be IPSS ≥ INT-2, Blasts <5%.

High Risk Patients:

• Acute myelogenous leukemia: Patients with CR2 are considered high risk if they have high risk cytogenetics, or molecular abnormalities or CR1 lasted for less than 1 year. Any evidence of active disease or no blasts in an acellular marrow.

• Acute Lymphocytic Leukemia: CR1- with Ph+ disease, CR2/+ with any cytogenetics. Any evidence of active disease.

• Chronic myelogenous leukemia- CP2/+, AP1/+, resistant or intolerant to TKI.

• Hodgkin's or Non Hodgkin's lymphoma- Disease recurrence following an autologous transplant, or high risk disease not thought to benefit from autologous transplant.

• Chronic lymphocytic leukemia- that is resistant to fludarabine, and never has been in remission or with stable disease/progressive disease

• Multiple myeloma: Must have had prior treatment. Patients in CR2 or greater can be considered, must have already failed autologous transplant Previous autologous transplant,must have been greater than 6 months prior to undergoing this transplant.

• Myelodysplastic syndrome: RAEB

• Other Myeloproliferative disorders including myelofibrosis, spent phase p Vera,Essential thrombocytosis,CMML.

Exclusion Criteria:

• Patients <18 years old Disease related criteria

• APML, presence of t(15,17) in first CR

• Patients with good risk AML, for example t(8;21), or inv 16, or normal cytogenetics with FLT-3-ITD negative, NPM-1 positive disease in 1st CR

• MDS IPSS < INT-2 Miscellaneous Criteria

• Recipients who have a matched related sibling or unrelated donor

• If recipient has evidence of anti-HLA antibodies directed against cord or haplo-donor as determined byflowPRA.

Underlying health criteria:

• Zubrod performance status > 2 (see Appendix E)

• Life expectancy is limited to less than 8 weeks by concomitant illness

• Patients with severely decreased LVEF (EF < 40%)

• Impaired pulmonary function tests (PFT's) (FVC, FEV1, DLCO < 45% predicted)

• Estimated Creatinine Clearance <50 ml/min

• Serum bilirubin> 2.0 mg/dl or SGPT >3 x upper limit of normal

• Evidence of chronic active hepatitis or cirrhosis

• HIV-positive

• Patient is pregnant

• Patient or guardian not able to provide informed consent

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Medical College of Wisconsin

Investigators

• Principal Investigator: Jeanne Palmer, M.D., Medical College of Wisconsin

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Parameswaran Hari, Professor of Medicine, Medical College of Wisconsin
• ClinicalTrials.gov Identifier: NCT01050946
• Other Study ID Numbers: MCW 11491
• First Posted: Jan 18, 2010
• Last Update Posted: Nov 20, 2015
• Last Verified: Oct 1, 2015

• Keywords provided by Parameswaran Hari, Professor of Medicine, Medical College of Wisconsin: Unrelated Umbilical Cord Blood Transplant(UCB); CD34+ Selected mismatched related donor; Haploidentical donor; hematopoietic stem cell transplantation(HSCT); ALL; Leukemia, Lymphocytic, Acute; AML; Leukemia, Myelocytic, Acute; CML; Leukemia, Myeloid, Chronic; NHL; Lymphoma, Non-Hodgkin; HL; Lymphoma, Hodgkins
• Additional relevant MeSH terms: Lymphoma; Leukemia; Lymphoma, Non-Hodgkin; Leukemia, Myeloid; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Hodgkin Disease

Study Results

Participant Flow

Recruitment Details	FDA approval was granted on 6/18/11 and went into effect on 7/18/11.Recruitment period started from the 7/18/11 until study closure on 3/28/13, All recruitment took place in the clinic setting. Only one patient was accrued.

Arm/Group Title	Haploidentical/Cord Transplant
Arm/Group Description	Haploidentical/cord transplant with the preconditioning regimen at discretion of treating physician. Haploidentical/cord transplant : Myeloablative preparative regimen of chemotherapy and radiation followed by mismatch related(haploidentical)donor and one unit umbilical cord blood transplantation. Conditioning Regimens Choice of regimen at the discretion of the treating physician Fludarabine 30mg/m2(Days-7,-6,-5,-4,-3)-,Melphalan 70mg/m2(Day -3,-2), ATG 1.5mg/m2(Day-7,-5,-3,-1) Fludarabine 50mg/m2(Day -6,-5,-4,-3,-2),Busulfan 3.2mg/kg(Day -5,-4,-3,-2),400cGY Total Body Irradiation(TBI)Day-1,ATG 1.5mg/kg(Day-7,-5,-3,-1) Day 0 -Haploidentical donor and one umbilical cord blood unit infusion
Period Title: Overall Study
STARTED	1
COMPLETED	1
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Haploidentical/Cord Transplant
Arm/Group Description	Haploidentical/cord transplant with the precondition regimen at discretion of treating physician. Haploidentical/cord transplant : Myeloablative preparative regimen of chemotherapy and radiation followed by mismatch related(haploidentical)donor and one unit umbilical cord blood transplantation. Conditioning Regimens Choice of regimen at the discretion of the treating physician Fludarabine 30mg/m2(Days-7,-6,-5,-4,-3)-,Melphalan 70mg/m2(Day -3,-2), ATG 1.5mg/m2(Day-7,-5,-3,-1) Fludarabine 50mg/m2(Day -6,-5,-4,-3,-2),Busulfan 3.2mg/kg(Day -5,-4,-3,-2),400cGY Total Body Irradiation(TBI)Day-1,ATG 1.5mg/kg(Day-7,-5,-3,-1) Day 0 -Haploidentical donor and one umbilical cord blood unit infusion
Overall Participants	1
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61
Sex: Female, Male (Count of Participants)
Female	1 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	The Primary Objective is to Estimate the Overall Survival, Separately in the Two Risk Strata.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Only one patient enrolled on study. Patient died prior to time frame of 3 years. It is not possible to assess this outcome measure.

Arm/Group Title	Haploidentical/Cord Transplant
Arm/Group Description	Haploidentical/cord transplant with the precondition regimen at discretion of treating physician. Haploidentical/cord transplant: Myeloablative preparative regimen of chemotherapy and radiation followed by mismatch related(haploidentical)donor and one unit umbilical cord blood transplantation. Conditioning Regimens Choice of regimen at the discretion of the treating physician Fludarabine 30mg/m2(Days-7,-6,-5,-4,-3)-,Melphalan 70mg/m2(Day -3,-2), ATG 1.5mg/m2(Day-7,-5,-3,-1) Fludarabine 50mg/m2(Day -6,-5,-4,-3,-2),Busulfan 3.2mg/kg(Day -5,-4,-3,-2),400cGY Total Body Irradiation(TBI)Day-1,ATG 1.5mg/kg(Day-7,-5,-3,-1) Day 0 -Haploidentical donor and one umbilical cord blood unit infusion
Measure Participants	0

2. Secondary Outcome

Title	Time to Relapse: To Assess the Incidence of Acute Leukemia or Lymphoma Relapse From Day of Transplant
Description	NOT analyzed since there was only patient and no relapse was observed till patient passed away
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Patient did not live to 2 years, no relapse observed

Arm/Group Title	Haploidentical/Cord Transplant
Arm/Group Description	Haploidentical/cord transplant with the preconditioning regimen at discretion of treating physician. Haploidentical/cord transplant : Myeloablative preparative regimen of chemotherapy and radiation followed by mismatch related(haploidentical)donor and one unit umbilical cord blood transplantation. Conditioning Regimens Choice of regimen at the discretion of the treating physician Fludarabine 30mg/m2(Days-7,-6,-5,-4,-3)-,Melphalan 70mg/m2(Day -3,-2), ATG 1.5mg/m2(Day-7,-5,-3,-1) Fludarabine 50mg/m2(Day -6,-5,-4,-3,-2),Busulfan 3.2mg/kg(Day -5,-4,-3,-2),400cGY Total Body Irradiation(TBI)Day-1,ATG 1.5mg/kg(Day-7,-5,-3,-1) Day 0 -Haploidentical donor and one umbilical cord blood unit infusion
Measure Participants	0

3. Secondary Outcome

Title	Time to Neutrophil Engraftment: To Assess the Incidence of Neutrophil Engraftment From Day of Transplant
Description	time to neutrophil recovery after transplant
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

Patient engrafted neutrophils and platelets but no statistical analysis possible

Arm/Group Title	Haploidentical/Cord Transplant
Arm/Group Description	Haploidentical/cord transplant with the preconditioning regimen at discretion of treating physician. Haploidentical/cord transplant : Myeloablative preparative regimen of chemotherapy and radiation followed by mismatch related(haploidentical)donor and one unit umbilical cord blood transplantation. Conditioning Regimens Choice of regimen at the discretion of the treating physician Fludarabine 30mg/m2(Days-7,-6,-5,-4,-3)-,Melphalan 70mg/m2(Day -3,-2), ATG 1.5mg/m2(Day-7,-5,-3,-1) Fludarabine 50mg/m2(Day -6,-5,-4,-3,-2),Busulfan 3.2mg/kg(Day -5,-4,-3,-2),400cGY Total Body Irradiation(TBI)Day-1,ATG 1.5mg/kg(Day-7,-5,-3,-1) Day 0 -Haploidentical donor and one umbilical cord blood unit infusion
Measure Participants	0

4. Secondary Outcome

Title	Time to Platelet Engraftment: To Assess the Incidence of Platelet Engraftment From Day of Transplant,
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

No further analysis reported as only one patient enrolled

Arm/Group Title	Haploidentical/Cord Transplant
Arm/Group Description	Haploidentical/cord transplant with the preconditioning regimen at discretion of treating physician. Haploidentical/cord transplant : Myeloablative preparative regimen of chemotherapy and radiation followed by mismatch related(haploidentical)donor and one unit umbilical cord blood transplantation. Conditioning Regimens Choice of regimen at the discretion of the treating physician Fludarabine 30mg/m2(Days-7,-6,-5,-4,-3)-,Melphalan 70mg/m2(Day -3,-2), ATG 1.5mg/m2(Day-7,-5,-3,-1) Fludarabine 50mg/m2(Day -6,-5,-4,-3,-2),Busulfan 3.2mg/kg(Day -5,-4,-3,-2),400cGY Total Body Irradiation(TBI)Day-1,ATG 1.5mg/kg(Day-7,-5,-3,-1) Day 0 -Haploidentical donor and one umbilical cord blood unit infusion
Measure Participants	0

5. Secondary Outcome

Title	Time to Acute GVHD: We Will Assess the Incidence and Severity of Grades II-IV and Grades III-IV Acute GVHD From Day of Transplant.
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

only one participant - no analysis done

Arm/Group Title	Haploidentical/Cord Transplant
Arm/Group Description	Haploidentical/cord transplant with the preconditioning regimen at discretion of treating physician. Haploidentical/cord transplant : Myeloablative preparative regimen of chemotherapy and radiation followed by mismatch related(haploidentical)donor and one unit umbilical cord blood transplantation. Conditioning Regimens Choice of regimen at the discretion of the treating physician Fludarabine 30mg/m2(Days-7,-6,-5,-4,-3)-,Melphalan 70mg/m2(Day -3,-2), ATG 1.5mg/m2(Day-7,-5,-3,-1) Fludarabine 50mg/m2(Day -6,-5,-4,-3,-2),Busulfan 3.2mg/kg(Day -5,-4,-3,-2),400cGY Total Body Irradiation(TBI)Day-1,ATG 1.5mg/kg(Day-7,-5,-3,-1) Day 0 -Haploidentical donor and one umbilical cord blood unit infusion
Measure Participants	0

6. Secondary Outcome

Title	Transplant Related Mortality (TRM): TRM is Death Occurring in Patients in Continuous Complete Remission.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

only pt who was enrolled died of TRM

Arm/Group Title	Haploidentical/Cord Transplant
Arm/Group Description	Haploidentical/cord transplant with the preconditioning regimen at discretion of treating physician. Haploidentical/cord transplant : Myeloablative preparative regimen of chemotherapy and radiation followed by mismatch related(haploidentical)donor and one unit umbilical cord blood transplantation. Conditioning Regimens Choice of regimen at the discretion of the treating physician Fludarabine 30mg/m2(Days-7,-6,-5,-4,-3)-,Melphalan 70mg/m2(Day -3,-2), ATG 1.5mg/m2(Day-7,-5,-3,-1) Fludarabine 50mg/m2(Day -6,-5,-4,-3,-2),Busulfan 3.2mg/kg(Day -5,-4,-3,-2),400cGY Total Body Irradiation(TBI)Day-1,ATG 1.5mg/kg(Day-7,-5,-3,-1) Day 0 -Haploidentical donor and one umbilical cord blood unit infusion
Measure Participants	1
Number [participants]	1 100%

7. Secondary Outcome

Title	Disease-free Survival:Death or Relapse Will be Considered Events for This Endpoint.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Haploidentical/Cord Transplant
Arm/Group Description	Haploidentical/cord transplant with the preconditioning regimen at discretion of treating physician. Haploidentical/cord transplant : Myeloablative preparative regimen of chemotherapy and radiation followed by mismatch related(haploidentical)donor and one unit umbilical cord blood transplantation. Conditioning Regimens Choice of regimen at the discretion of the treating physician Fludarabine 30mg/m2(Days-7,-6,-5,-4,-3)-,Melphalan 70mg/m2(Day -3,-2), ATG 1.5mg/m2(Day-7,-5,-3,-1) Fludarabine 50mg/m2(Day -6,-5,-4,-3,-2),Busulfan 3.2mg/kg(Day -5,-4,-3,-2),400cGY Total Body Irradiation(TBI)Day-1,ATG 1.5mg/kg(Day-7,-5,-3,-1) Day 0 -Haploidentical donor and one umbilical cord blood unit infusion
Measure Participants	1
Number [participants]	0 0%

Adverse Events

Time Frame	From the time the patient signed consent until the patient's death.
Arm/Group Title	Haploidentical/Cord Transplant
Arm/Group Description	Haploidentical/cord transplant with the preconditioning regimen at discretion of treating physician. Haploidentical/cord transplant : Myeloablative preparative regimen of chemotherapy and radiation followed by mismatch related(haploidentical)donor and one unit umbilical cord blood transplantation. Conditioning Regimens Choice of regimen at the discretion of the treating physician Fludarabine 30mg/m2(Days-7,-6,-5,-4,-3)-,Melphalan 70mg/m2(Day -3,-2), ATG 1.5mg/m2(Day-7,-5,-3,-1) Fludarabine 50mg/m2(Day -6,-5,-4,-3,-2),Busulfan 3.2mg/kg(Day -5,-4,-3,-2),400cGY Total Body Irradiation(TBI)Day-1,ATG 1.5mg/kg(Day-7,-5,-3,-1) Day 0 -Haploidentical donor and one umbilical cord blood unit infusion
All Cause Mortality
	Haploidentical/Cord Transplant
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Haploidentical/Cord Transplant
	Affected / at Risk (%)	# Events
Total	1/1 (100%)
Infections and infestations
Death	1/1 (100%)	1
Psychiatric disorders
Confusion	1/1 (100%)	1
Renal and urinary disorders
Acute Renal Injury	1/1 (100%)	1
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome	1/1 (100%)	1
Other (Not Including Serious) Adverse Events
	Haploidentical/Cord Transplant
	Affected / at Risk (%)	# Events
Total	1/1 (100%)
Infections and infestations
Death	1/1 (100%)	1
Psychiatric disorders
Confusion	1/1 (100%)	1
Renal and urinary disorders
Acute Renal Injury	1/1 (100%)	1
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome	1/1 (100%)	1

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.