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

Randomized Phase II Trial of Bulk Versus Fractionated Stem Cell Infusions in Patients With Hematologic Malignancies Undergoing Stem Cell Transplantation

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.

Study Overview

• Status: Completed
• Conditions: Leukemia
• Intervention / Treatment: Procedure: allogeneic hematopoietic stem cell transplantation; 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.

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Program Manual, document E-1 see http://mskweb5.mskcc.org/intranet/html/80312.cfm
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Time to Engraftment of Neutrophils	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. Determing the median time to ANC of >/= 0.5 x 10^9/L	Up to 100 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Assessed for Toxicities	Participants will be assessed for toxicities with the NCI-Common Terminology for Adverse Events (CTCAE), version 4.0.	2 years
Median Time to Platelet Engraftment	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. Determine days to platelet engraftment by platelet count.	Up to 365 days
Overall Survival	Percentage of participants alive at 24 months	24 months
Hematopoietic Function on Day 30	Determine the difference of CD4+ lymphocyte recovery between the two arms on day 30	30 days
Hematopoietic Function on Day 180	Determine the difference of CD4+ lymphocyte recovery between the two arms on day 180	180 days
Hematopoietic Function on Day 360	Determine the difference of CD4+ lymphocyte recovery between the two arms on day 360	360 days

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2012
• Primary Completion (Actual): August 30, 2021
• Study Completion (Actual): August 30, 2021

Study Registration Dates

• First Submitted: May 9, 2012
• First Submitted That Met QC Criteria: May 9, 2012
• First Posted (Estimate): May 10, 2012

Study Record Updates

• Last Update Posted (Estimate): December 29, 2022
• Last Update Submitted That Met QC Criteria: December 1, 2022
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Multiple Myeloma; Myelodysplastic syndrome; Acute Leukemia; Non Hodgkins Lymphoma; CliniMACS-CD34 Reagent System; Hodgkins Disease; 12-016
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms
• Other Study ID Numbers: 12-016