Bulk Versus Fractionated Stem Cell Infusions in Patients With Hematologic Malignancies Undergoing Stem Cell Transplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01596257
First received: May 9, 2012
Last updated: August 25, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to find out if getting a blood stem cell transplant with donor stem cells given over several days is better than getting a blood stem cell transplant with donor stem cells given over 1 day. We want to find out which procedure over will result in improved recovery of blood and immune function after transplant. When donor stem cells are given over various days in mice, the blood and immune system recovery is quicker.


Condition Intervention Phase
Leukemia
Procedure: allogeneic hematopoietic stem cell transplantation
Device: CliniMACS
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II Trial of Bulk Versus Fractionated Stem Cell Infusions in Patients With Hematologic Malignancies Undergoing Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • neutrophil recovery [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Determine the effects of fractionated vs. bulk stem cell infusions on neutrophil recovery as defined by number of days with an absolute neutrophil count of less than 500 neutrophils per micro liter and time to an absolute neutrophil count (ANC) of 500.


Secondary Outcome Measures:
  • safety [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Toxicities will be graded on a scale of 0 to 4 as described by the NCI-Common Terminology for Adverse Events (CTCAE), version 4.0.

  • immune- reconstitution [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    The area under the hematopoietic recovery curve for the factors: ALC, CD4, CD8, and platelet count. The area under the curve will be computed based on recordings at days 30, 60, 100, 180, 365.

  • on bacterial, viral, and fungal infections during the first 100 days post transplant [ Time Frame: 100 days post days transplant ] [ Designated as safety issue: No ]
    The time to ALC 500, and the time to first bacterial, viral, and fungal infection will be computed using the cumulative incidence function and a comparison between groups will be undertaken using Gray's test.

  • hematopoietic function [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]
    Determine the effect of fractionated vs bulk CD34 selected stem cell infusions on hematopoietic function as determined by platelet counts and cumulative platelet transfusion requirements on days 30, 60 and 100, 6 and 12 months post transplant.


Estimated Enrollment: 72
Study Start Date: May 2012
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: bulk SCT
Patients receive reduced intensity or myeloablative conditioning regimen, GVHD prophylaxis, and undergo T cell depleted or no T cell depleted allogeneic SCT on day 0. After completion of study treatment, patients are followed up every 6-8 weeks for up to 24 months
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo allogeneic hematopoietic stem cell transplant
Device: CliniMACS
Experimental: fractionated SCT
Patients receive reduced intensity or myeloablative conditioning regimen, GVHD prophylaxis, and undergo T cell depleted or no T cell depleted allogeneic SCT on days 0, 2, 4, and 6. After completion of study treatment, patients are followed up every 6-8 weeks for up to 24 months
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo allogeneic hematopoietic stem cell transplant
Device: CliniMACS

Detailed Description:

This is a complex study that involves various interventions, Intervention #1: Donor Initial Stem Cell Collection; Intervention #2: Stem Cell Product Initial Processing Orders; Intervention #3 Patient Admission and Transplantation; Intervention #4: Stem cell infusion; Intervention #5: Post infusion follow up; Intervention #6: Off Study Patient and Donor Evaluation.

Patients whose donor fails to collect the appropriate number of cells will receive all their cells as a bulk infusion. These patients will continue to receive a transplant on protocol but will be replaced until both arms have reached the target accrual.

  Eligibility

Ages Eligible for Study:   up to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Patients who are considered candidates for an allogeneic stem cell transplantation as treatment for any of the following hematologic disorders:
  • Acute Leukemia
  • Myelodysplastic syndrome
  • Other myeloproliferative disorder (i.e. myelofibrosis, chronic myelomonocytic leukemia, or chronic myelogenous leukemia)
  • Non Hodgkins Lymphoma
  • Hodgkins Disease
  • Multiple Myeloma
  • Age includes from birth to < 75 years old.
  • Patients must have a Karnofsky (adult) or Lansky (pediatric) Performance Status > 70%
  • Patients must have adequate organ function measured by:
  • Cardiac: asymptomatic or if symptomatic then LVEF at rest must be > 40%
  • Hepatic: < 5x ULN ALT and < 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia.
  • Renal: serum creatinine <1.5 mg/dl or if serum creatinine is outside the normal range, then CrCl > 40 ml/min (measured or calculated/estimated)
  • Pulmonary: asymptomatic or if symptomatic, DLCO > 40% of predicted (corrected for hemoglobin).

Exclusion Criteria:

  • Female patients who are pregnant or breast-feeding.
  • Active viral, bacterial or fungal infection
  • Patient seropositive for HIV-I/II; HTLV -I/II
  • Presence of leukemia in the CNS
  • Candidate for a protocol of higher priority. For the purpose of this study, the following protocols will be considered of higher priority: 10-051 Donor Inclusion Criteria
  • HLA compatible related or unrelated donor, (i.e. a fully matched unmanipulated grafts or 1-2 HLA allele disparate donor for CD34 selected grafts).
  • Meets criteria outlined in the FACT-approved SOP for "DONOR EVALUATION AND SELECTION FOR ALLOGENEIC TRANSPLANTATION" in the Blood and Marrow Transplant
  • Donor must have adequate peripheral venous catheter access for leukapheresis or must agree to placement of a central catheter.
  • Wt >25kg

Donor Exclusion Criteria

  • Evidence of active infection (including urinary tract infection, or upper respiratory tract Infection) or viral hepatitis exposure (on screening), unless only HBS Ab+ and HBV DNA negative.
  • Medical or physical reason which makes the donor unlikely to tolerate or cooperate with growth factor therapy and leukapheresis.
  • Factors which place the donor at increased risk for complications from leukapheresis or GCSF therapy (e.g., autoimmune disease, sickle cell trait, symptomatic coronary artery disease requiring therapy).
  • Pregnancy (positive serum or urine β-HCG) or breastfeeding. Women of childbearing age must avoid becoming pregnant while on the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01596257

Contacts
Contact: Sergio Giralt, MD 212-639-6009
Contact: Richard O'Reilly, MD 212-639-5956

Locations
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Sergio Giralt, MD    212-639-6009      
Contact: Richard O'Reilly, MD    212-639-5956      
Principal Investigator: Sergio Giralt, MD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Sergio Giralt, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01596257     History of Changes
Other Study ID Numbers: 12-016
Study First Received: May 9, 2012
Last Updated: August 25, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
CliniMACS-CD34 Reagent System
Acute Leukemia
Myelodysplastic syndrome
Non Hodgkins Lymphoma
Hodgkins Disease
Multiple Myeloma
12-016

Additional relevant MeSH terms:
Leukemia
Hematologic Neoplasms
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Hematologic Diseases

ClinicalTrials.gov processed this record on August 28, 2014