Umbilical Cord Blood (UCB) Transplantation in Pediatric Patients With High Risk Leukemia and Myelodysplasia

• Sponsor: University of Miami (Other)
• Overall Status: Completed
• CT.gov ID: NCT02007863
• Collaborator: (none)
• Enrollment: 2
• Locations: 2
• Arm: 1
• Duration (Months): 70
• Patient Per Site: 1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Unrelated Cord Blood (UCB) transplant in children is a viable stem cell transplant modality for patients with leukemia and myelodysplasia. UCB is now considered "Standard Of Care" in cases where a suitable living bone marrow donor is not available. The survival of UCB is similar to Matched Unrelated Marrow Transplant. This study is considered "Research" since UCB is not a licensed product and requires investigational new drug (IND). THERE ARE NO SPECIFIC RESEARCH QUESTIONS IN THIS PROTOCOL. This protocol merely provides UCB as a stem cell treatment modality to pediatric patients who may require it after a conditioning regimen that excludes Total Body Irradiation.

Condition or Disease	Intervention/Treatment	Phase
Leukemia; Myelodysplasia; Acute Lymphocytic Leukemia; Acute Myelogenous Leukemia	Procedure: Umbilical Cord Blood Transfusion; Drug: Fludarabine; Drug: Busulfan; Drug: Melphalan	N/A

Detailed Description

The preparative regimen will consist of:

• Fludarabine: 25 mg/m2/day IV x 5 doses on Days -13, to -9

• Busulfan 1mg/kg IV every 6 hrs x 16 doses on Days -8 to -5

• Melphalan 45 mg/m2/day IV x 3 doses on days -4 to -2

• ATGAM 30mg/kg/day x 3 doses on Days -3 to -1

• Day 0 will be the day of the UCB Transplant

• The graft-versus-host-disease (GVHD) prophylaxis will be Cyclosporin A to maintain level 200-400 beginning on Day -3, through 200-400. Solumedrol at 1mg/kg/day on Day 1 until D+4, then solumedrol 2mg/kg/day until Day +19 or till absolute neutrophil count (ANC) reaches 500/mm2, then taper by 0.2 mg/kg/week.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment Protocol: Umbilical Cord Blood (UCB) Transplantation in Pediatric Patients With High Risk Leukemia and Myelodysplasia Using Conditioning Regimen Without Radiation
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Umbilical Cord Blood + Chemotherapy Umbilical Cord Blood transfusion + Chemotherapy (Fludarabine + Busulfan + Melphalan)

Procedure: Umbilical Cord Blood Transfusion; Following the administration of the preparative therapy, all subjects will undergo UCB transplantation. Umbilical Cord Blood Transfusion will occur on Day 0; Other Names: UCB ; Drug: Fludarabine; Fludarabine 25 mg/m2/day will be administered over 30-60 minutes intravenous infusion on Days -13 through -9 for a total of 5 doses. Fludarabine will not be dose adjusted for body weight.; Other Names: Fludara ; Drug: Busulfan; Busulfan IV (Busulfex) will be administered IV every 6 hours on days -8 through -5 for a total of 16 doses. Seizure prophylaxis prior to first dose of busulfan till Day -3 will be administered.; Other Names: Busulfex ; Drug: Melphalan; Melphalan 45 mg/m2/day will be administered over 60 minutes intravenous infusion on Days -4 through -2 for a total of 3 doses.; Other Names: Alkeran

Outcome Measures

Primary Outcome Measures

1. Number of Successful Unrelated Cord Blood (UCB) Transplants [2 Years]

   The number of patients who received successful UCB transplants as evidenced by absolute neutrophil recovery.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must be up to 21 years of age

• Patients cannot receive total body irradiation (TBI) because of:

• Young age - < 2 years at diagnosis of leukemia resulting in an age < 4 years at transplantation (due to risk of severe growth retardation and brain damage).

• Inability to tolerate TBI because of prior radiation or organ toxicity.

• Refractory/multiply relapsed leukemia, for which a traditional TBI/cyclophosphamide regimen would unlikely lead to a successful outcome.

• Patients must have a partially human leukocyte antigen (HLA)-matched UCB unit. Unit must be HLA-matched minimally at 4 of 6 HLA-A and B (at intermediate resolution by molecular typing) and DRB1 (at high resolution by molecular typing) loci with the patient. The unit must deliver a pre-cryopreserved nucleated cell dose of at least 2.5 x 10^7 per kilogram.

• Acute myelogenous leukemia (AML) at the following stages:

• High risk first complete remission (CR1), defined as:

• Having preceding myelodysplasia (MDS)

• High risk cytogenetics (High-risk cytogenetics: del (5q) -5, -7, abn (3q), t (6;9) complex karyotype (>= 5 abnormalities)

• Requiring > 2 cycles chemotherapy to obtain CR;

• Second or greater CR.

• First relapse with < 25% blasts in bone marrow.

• Patients with therapy-related AML whose prior malignancy has been in remission for at least 12 months.

• Acute lymphocytic leukemia (ALL) at the following stages:

• High risk first remission, defined as:

1. Ph+ ALL; or,

2. Myeloid/lymphoid leukemia (MLL) rearrangement with slow early response [defined as having M2 (5-25% blasts) or M3 (>25% blasts on bone marrow examination on Day 14 of induction therapy)]; or,

3. Hypodiploidy (< 44 chromosomes or DNA index < 0.81); or,

4. End of induction M3 bone marrow; or,

5. End of induction M2 with M2-3 at Day 42.

• High risk second remission, defined as:

1. Bone marrow relapse < 36 months from induction; or,

2. T-lineage relapse at any time; or,

3. Very early isolated central nervous system (CNS) relapse (6 months from diagnosis); or,

4. Slow reinduction (M2-3 at Day 28) after relapse at any time.

• Any third or subsequent CR.

• Biphenotypic or undifferentiated leukemia in any CR or if in 1st relapse must have < 25% blasts in bone marrow (BM).

• MDS at any stage.

• Chronic myelogenous leukemia (CML) in chronic or accelerated phase.

• All patients with evidence of CNS leukemia must be treated and be in CNS CR to be eligible for study.

• Patients ≥ 16 years old must have a Karnofsky score ≥ 70% and patients < 16 years old must have a Lansky score ≥ 70%.

• Signed informed consent.

• Patients with adequate physical function as measured by:

1. Cardiac: Left ventricular ejection fraction at rest must be > 40%, or shortening fraction > 26%

2. Hepatic: Bilirubin ≤ 2.5 mg/dL; and alanine transaminase (ALT), aspartate transaminase (AST) and Alkaline Phosphatase ≤ 5 x upper limit of normal (ULN)

3. Renal: Serum creatinine within normal range for age, or if serum creatinine outside normal range for age, then renal function (creatinine clearance or GFR) > 70 mL/min/1.73 m2.

4. Pulmonary: Diffusing capacity of the lungs for carbon monoxide (DLCO), Forced expiratory volume in 1 second (FEV1), Forced vital capacity (FVC) (diffusion capacity) > 50% of predicted (corrected for hemoglobin); if unable to perform pulmonary function tests, then O2 saturation > 92% of room air.

Exclusion Criteria:

• Pregnant (B-positive HCG) or breastfeeding.

• Evidence of HIV infection or HIV positive serology.

• Current uncontrolled bacterial, viral or fungal infection (currently taking medication and progression of clinical symptoms).

• Autologous transplant < 6 months prior to enrollment.

• Prior autologous transplant for the disease for which the UCB transplant will be performed.

• Allogeneic hematopoietic stem cell transplant < 6 months prior to enrollment.

• Active malignancy other than the one for which the UCB transplant is being performed within 12 months of enrollment

• Active CNS leukemia.

• Requirement of supplemental oxygen.

• HLA-matched related donor able to donate.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jackson Memorial Hospital	Miami	Florida	United States	33136
2	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136

Sponsors and Collaborators

• University of Miami

Investigators

• Principal Investigator: Martin Andreasky, MD, PhD, University of Miami

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Martin Andreansky, Associate Professor of Clinical, University of Miami
• ClinicalTrials.gov Identifier: NCT02007863
• Other Study ID Numbers: 20080774
• First Posted: Dec 11, 2013
• Last Update Posted: Dec 28, 2015
• Last Verified: Nov 1, 2015

• Keywords provided by Martin Andreansky, Associate Professor of Clinical, University of Miami: Leukemia; Myelodysplasia; Acute lymphocytic leukemia; ALL; Acute myelogenous leukemia; AML; Pediatric
• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Preleukemia; Myelodysplastic Syndromes; Fludarabine; Melphalan; Busulfan

Study Results

Participant Flow

Arm/Group Title	Umbilical Cord Blood + Chemotherapy
Arm/Group Description	Umbilical Cord Blood Transfusion: Following the administration of the preparative therapy, all subjects will undergo UCB transplantation. Umbilical Cord Blood Transfusion will occur on Day 0 Fludarabine: Fludarabine 25 mg/m2/day will be administered over 30-60 minutes intravenous infusion on Days -13 through -9 for a total of 5 doses. Fludarabine will not be dose adjusted for body weight. Busulfan: Busulfan IV (Busulfex) will be administered IV every 6 hours on days -8 through -5 for a total of 16 doses. Seizure prophylaxis prior to first dose of busulfan till Day -3 will be administered. Melphalan: Melphalan 45 mg/m2/day will be administered over 60 minutes intravenous infusion on Days -4 through -2 for a total of 3 doses.
Period Title: Overall Study
STARTED	2
COMPLETED	2
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Umbilical Cord Blood + Chemotherapy
Arm/Group Description	Umbilical Cord Blood Transfusion: Following the administration of the preparative therapy, all subjects will undergo UCB transplantation. Umbilical Cord Blood Transfusion will occur on Day 0 Fludarabine: Fludarabine 25 mg/m2/day will be administered over 30-60 minutes intravenous infusion on Days -13 through -9 for a total of 5 doses. Fludarabine will not be dose adjusted for body weight. Busulfan: Busulfan IV (Busulfex) will be administered IV every 6 hours on days -8 through -5 for a total of 16 doses. Seizure prophylaxis prior to first dose of busulfan till Day -3 will be administered. Melphalan: Melphalan 45 mg/m2/day will be administered over 60 minutes intravenous infusion on Days -4 through -2 for a total of 3 doses.
Overall Participants	2
Age (Count of Participants)
<=18 years	2 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	1 50%
Male	1 50%
Region of Enrollment (participants) [Number]
United States	2 100%

Outcome Measures

1. Primary Outcome

Title	Number of Successful Unrelated Cord Blood (UCB) Transplants
Description	The number of patients who received successful UCB transplants as evidenced by absolute neutrophil recovery.
Time Frame	2 Years

Outcome Measure Data

Analysis Population Description

THERE ARE NO SPECIFIC RESEARCH QUESTIONS IN THIS PROTOCOL. This protocol merely provides UCB as a stem cell treatment modality to pediatric patients who may require it after a conditioning regimen that excludes Total Body Irradiation.Unrelated Cord Blood (UCB) transplant

Arm/Group Title	Umbilical Cord Blood + Chemotherapy
Arm/Group Description	Umbilical Cord Blood Transfusion: Following the administration of the preparative therapy, all subjects will undergo UCB transplantation. Umbilical Cord Blood Transfusion will occur on Day 0 Fludarabine: Fludarabine 25 mg/m2/day will be administered over 30-60 minutes intravenous infusion on Days -13 through -9 for a total of 5 doses. Fludarabine will not be dose adjusted for body weight. Busulfan: Busulfan IV (Busulfex) will be administered IV every 6 hours on days -8 through -5 for a total of 16 doses. Seizure prophylaxis prior to first dose of busulfan till Day -3 will be administered. Melphalan: Melphalan 45 mg/m2/day will be administered over 60 minutes intravenous infusion on Days -4 through -2 for a total of 3 doses.
Measure Participants	2
Number [participants]	2 100%

Adverse Events

Arm/Group Title	Umbilical Cord Blood + Chemotherapy
Arm/Group Description	Umbilical Cord Blood Transfusion: Following the administration of the preparative therapy, all subjects will undergo UCB transplantation. Umbilical Cord Blood Transfusion will occur on Day 0 Fludarabine: Fludarabine 25 mg/m2/day will be administered over 30-60 minutes intravenous infusion on Days -13 through -9 for a total of 5 doses. Fludarabine will not be dose adjusted for body weight. Busulfan: Busulfan IV (Busulfex) will be administered IV every 6 hours on days -8 through -5 for a total of 16 doses. Seizure prophylaxis prior to first dose of busulfan till Day -3 will be administered. Melphalan: Melphalan 45 mg/m2/day will be administered over 60 minutes intravenous infusion on Days -4 through -2 for a total of 3 doses.
All Cause Mortality
	Umbilical Cord Blood + Chemotherapy
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Umbilical Cord Blood + Chemotherapy
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Other (Not Including Serious) Adverse Events
	Umbilical Cord Blood + Chemotherapy
	Affected / at Risk (%)	# Events
Total	0/2 (0%)

Limitations/Caveats

THERE ARE NO SPECIFIC RESEARCH QUESTIONS IN THIS PROTOCOL. This protocol merely provides UCB as a stem cell treatment modality to pediatric patients who may require it after a conditioning regimen that excludes Total Body Irradiation.

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.