G-CSF PMRD: Granulocyte Colony Stimulating Factor (G-CSF) Stimulated Bone Marrow and In Vivo T-Cell Depletion in Patients With Hematologic Malignancies or Bone Marrow Failure Syndrome

• Sponsor: Emory University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00228813
• Collaborator: (none)
• Enrollment: 8
• Location: 1
• Arm: 1
• Duration (Months): 129
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purposes of this study are:

• To examine the engraftment rate in patients receiving in vivo T-cell-depleted G-CSF stimulated bone marrow from partially mismatched related donors.

• To evaluate the incidence and severity of acute and chronic graft-versus-host disease in patients receiving in vivo T-cell-depleted G-CSF stimulated bone marrow from partially mismatched related donors.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Malignancies	Drug: Granulocyte Colony Stimulating Factor	N/A

Detailed Description

This study is a single-arm, non-randomized feasibility study. Patients meeting the criteria for this study will be entered sequentially until completion or closure of the study. Early stopping rules will be employed to ascertain whether an unacceptable rate of toxicity (non-engraftment, and/or acute GVHD) occurs.

Patients will be prepared for transplant through the administration of the following conditioning regimen based on their primary disease:

• Total body irradiation (1400 rads in 8 fractionated doses) and high dose chemotherapy, including cytosine arabinoside, etoposide, and cyclophosphamide. Patients with bone marrow failure syndrome will not receive etoposide in the conditioning regimen.

• Post transplant immunosuppression prophylaxis against acute GVHD will include sequential administration of cyclosporine, methotrexate, basiliximab and mycophenolate.

• The donor will receive 3 daily G-CSF injections prior to marrow harvest starting on day -3. The injections may be initiated by the donor's primary physician prior to donor's arrival, or by the BMT service at Children's Healthcare of Atlanta.

• Patients will receive daily GM-CSF injections (250 mcg/m2) starting from day +7 post transplant until absolute neutrophil count (ANC) is greater than 2,000/µL for three days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Feasibility Study of Using G-CSF Stimulated Bone Marrow and In Vivo T-Cell Depletion in Patients With Hematologic Malignancies or Bone Marrow Failure Syndrome With Partially Mismatched Related Donors
• Study Start Date: Apr 1, 2004
• Actual Primary Completion Date: Jan 1, 2015
• Actual Study Completion Date: Jan 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Other: Granulocyte Colony Stimulating Factor (G-CSF) stimulation Participants will receive bone marrow from donors who undergo Granulocyte Colony Stimulating Factor (G-CSF) stimulation prior to bone marrow collection.

Drug: Granulocyte Colony Stimulating Factor; FILGRASTIM: G-CSF (NEUPOGEN®) is administered as a short IV infusion over 30 minutes or subcutaneously. It is given beginning on day -3 for 3 days to the donor prior to the bone marrow harvest. Drug Information: FILGRASTIM: G-CSF (Neupogen®) Formulation: G-CSF is available as a preservative-free solution for injection in 1.0 ml and 1.6 ml vials containing 300 mcg/ml. Administration: G-CSF 5 mcg/kg/d will be given subcutaneously or as a short I.V. infusion over 30 minutes. Recombinant GM-CSF at the dose of 250 mcg/m2 will be given intravenously from day +7 to help white counts recovery. The drug will be diluted in NS at a concentration of at least 10 mcg/ml. Drug Information: Sargramostim (Leukine) Formulation: 250 mcg, 500 mcg lyophlized powder for injection

Outcome Measures

Primary Outcome Measures

1. Engraftment Rate [Day 45]

   The number of participants who received in vivo T-cell-depleted G-CSF stimulated bone marrow from partially mismatched related donor who reached engraftment by Day 45.

2. Incidence of Acute Graft-versus-host Disease [Day 100]

   The number of participants diagnosed with new acute graft-versus-host disease (GVHD).

3. Incidence of Chronic Graft-versus-host Disease [Duration of Study (Up to two years)]

   The number of participants diagnosed with chronic graft-versus-host disease (GVHD).

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 22 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with hematologic malignancies or bone marrow failure syndrome who are candidates for allogeneic bone marrow transplantation are eligible for this study.

Hematologic malignancies indicated for transplantation:

• Acute lymphoblastic leukemia (ALL) in first remission (with high risk feature), 2nd or greater remission.

• Acute myeloid leukemia (AML) in first remission (with high risk feature), 2nd or greater remission.

• Chronic myeloid leukemia (CML) in 2nd chronic phase or accelerated phase.

• Juvenile myelomonocytic leukemia (JMML).

• Myelodysplastic syndrome.

• Biphenotypic leukemia in first (with high risk feature), 2nd or greater remission.

• Induction failure leukemia.

• Refractory relapsed leukemia.

• Bone marrow failure syndrome.

• Severe aplastic anemia failed immunotherapy.

• Patients who do not have a 6 out of 6 matched related or unrelated donor or 4/6 and 5/6 matched cord blood will be eligible for this study.

• Partially mismatched related donor availability as defined by molecular typing with 3 to 5 HLA matches.

• Patients who are under 22 years of age.

Exclusion Criteria:

• Patients will not be excluded based on sex, racial, or ethnic background.

• Patients will be excluded if they demonstrate significant functional deficits in major organs, which would obviously interfere with successful outcome following bone marrow transplant utilizing the following guidelines.

• Evidence of active, deep-seated, life-threatening infections for which there is no known effective therapy (certain fungal species, HIV, etc.).

• Patients who have been treated for infections must have appropriate responses as documented by 2 (two) consecutive negative cultures and/or stable radiographic examinations.

• Patients who have active central nervous system (CNS) leukemic disease.

• Patients will be excluded if they are women of childbearing potential who are currently pregnant (beta-HCG+) or who are not practicing adequate contraception.

• Patients who have had a previous hematopoietic stem cell transplant will be excluded.

• Donors will be excluded if they are sensitive to E. coli-derived protein.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Healthcare of Atlanta/Emory University	Atlanta	Georgia	United States	30322

Sponsors and Collaborators

• Emory University

Investigators

• Principal Investigator: Kuang-Yueh Chiang, M.D., Children's Healthcare of Atlanta/Emory University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Emory University
• ClinicalTrials.gov Identifier: NCT00228813
• Other Study ID Numbers: IRB00021819; 0159-2004
• First Posted: Sep 29, 2005
• Last Update Posted: Sep 11, 2017
• Last Verified: Aug 1, 2017

• Additional relevant MeSH terms: Neoplasms; Hematologic Neoplasms; Bone Marrow Failure Disorders; Pancytopenia; Lenograstim

Study Results

Participant Flow

Recruitment Details	Participants were recruited from Children's Healthcare of Atlanta between January 2005 and December 2013.

Arm/Group Title	Granulocyte Colony Stimulating Factor (G-CSF) Stimulation
Arm/Group Description	Participants with hematologic malignancies or bone marrow failure syndrome received in vivo T-cell depleted granulocyte colony stimulating factor (G-CSF) stimulated bone marrow from a partially mismatched related donor.
Period Title: Overall Study
STARTED	8
COMPLETED	4
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Granulocyte Colony Stimulating Factor (G-CSF) Stimulation
Arm/Group Description	Participants with hematologic malignancies or bone marrow failure syndrome received in vivo T-cell depleted granulocyte colony stimulating factor (G-CSF) stimulated bone marrow from a partially mismatched related donor.
Overall Participants	8
Age (Count of Participants)
<=18 years	7 87.5%
Between 18 and 65 years	1 12.5%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	2 25%
Male	6 75%

Outcome Measures

1. Primary Outcome

Title	Engraftment Rate
Description	The number of participants who received in vivo T-cell-depleted G-CSF stimulated bone marrow from partially mismatched related donor who reached engraftment by Day 45.
Time Frame	Day 45

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Granulocyte Colony Stimulating Factor (G-CSF) Stimulation
Arm/Group Description	Participants received bone marrow from donors who underwent Granulocyte Colony Stimulating Factor (G-CSF) stimulation prior to bone marrow collection.
Measure Participants	8
Number [particpants]	8

2. Primary Outcome

Title	Incidence of Acute Graft-versus-host Disease
Description	The number of participants diagnosed with new acute graft-versus-host disease (GVHD).
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

Participants who who developed acute GVHD was measured at Day 100 post bone marrow transplant.

Arm/Group Title	Granulocyte Colony Stimulating Factor (G-CSF) Stimulation
Arm/Group Description	Participants received bone marrow from donors who underwent Granulocyte Colony Stimulating Factor (G-CSF) stimulation prior to bone marrow collection.
Measure Participants	8
Number [participants]	6 75%

3. Primary Outcome

Title	Incidence of Chronic Graft-versus-host Disease
Description	The number of participants diagnosed with chronic graft-versus-host disease (GVHD).
Time Frame	Duration of Study (Up to two years)

Outcome Measure Data

Analysis Population Description

Participants who survived beyond Day 100 post bone marrow transplant.

Arm/Group Title	Granulocyte Colony Stimulating Factor (G-CSF) Stimulation
Arm/Group Description	Participants received bone marrow from donors who underwent Granulocyte Colony Stimulating Factor (G-CSF) stimulation prior to bone marrow collection.
Measure Participants	6
Number [participants]	2 25%

Adverse Events

Time Frame	Adverse events were collected throughout the duration of the study and follow up period (up to two years).
Arm/Group Title	Granulocyte Colony Stimulating Factor (G-CSF) Stimulation
Arm/Group Description	Participants with hematologic malignancies or bone marrow failure syndrome received in vivo T-cell depleted granulocyte colony stimulating factor (G-CSF) stimulated bone marrow from a partially mismatched related donor.
All Cause Mortality
	Granulocyte Colony Stimulating Factor (G-CSF) Stimulation
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Granulocyte Colony Stimulating Factor (G-CSF) Stimulation
	Affected / at Risk (%)	# Events
Total	4/8 (50%)
Blood and lymphatic system disorders
Recurrent Disease	2/8 (25%)	2
General disorders
Multi-organ system failure	2/8 (25%)	2
Other (Not Including Serious) Adverse Events
	Granulocyte Colony Stimulating Factor (G-CSF) Stimulation
	Affected / at Risk (%)	# Events
Total	0/8 (0%)

Limitations/Caveats

There was a small number of participants and a short follow up time period for this trial.

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.