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Fractionated Stem Cell Infusions in Myeloma Patients Undergoing Autologous Stem Cell Transplant

Primary Purpose

Multiple Myeloma

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Fractionated Stem Cell Infusions
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Stem cell Infusions, Autologous Stem Cell Transplant, 11-105

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age ≥18 and < than or = to 75
  • Histologic and serologic findings, reviewed at MSKCC, confirming the diagnosis of multiple myeloma. Standard diagnostic criteria for multiple myeloma will be used, as per the International Myeloma Foundation consensus guidelines (Durie et al, 2003) .
  • Patients must have symptomatic multiple myeloma who have responded to prior induction or salvage chemotherapy (i.e. chemosensitive disease):

    • Patients who are receiving high-dose melphalan and ASCT as part of their initial therapy require at least minor response to their last line of therapy to document chemosensitive disease (Anderson et al. 2008)
    • Patients who are receiving high-dose melphalan and ASCT as part of salvage therapy require at least a minor response to their last line of therapy to document chemosensitive disease (Anderson et al. 2008).
    • There is no limit on the number of prior regimens received by the patient.

      • Patients must have at least 7 x 10^6 (+/- 0.5 x 10^6) CD34+ stem cells/kg frozen if he/she is being treated as part of a salvage (second) transplant strategy; patients must have 10 x 10^6 (+/- 0.5 x 10^6) CD34+ stem cells/kg frozen if ASCT is being performed as part of initial therapy.
      • Adequate organ function is required, defined as follows:
    • Serum bilirubin ≤ 2.0 mg/dl
    • AST, ALT and alkaline phosphatase < 3 times the upper limit of laboratory normal
    • Creatinine clearance > or = to 40 ml/min (24 hour urine collection or calculated*)

      *To be calculated by the Cockroft-Gault method: (140-Age) x Mass (kg) x [0.85 if female] (72 x Creatinine (mg/dL)

    • LVEF > or = to 45% by MUGA or rest ECHO
    • Diffusing capacity > or = to 45% (adjusted for hemoglobin) predicted by pulmonary function testing
  • Performance status KPS > or = to 70%.

Exclusion Criteria:

  • Unstable angina or myocardial infarction within 4 months of initiating therapy on trial, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker
  • Pregnant or lactating females
  • Nonhematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas
  • Contraindication to melphalan or any of the required supportive treatments, including hypersensitivity to G-CSF or pegfilgrastim
  • Any other medical condition or laboratory evaluation that, in the treating physician's or principal investigator's opinion, makes the patient unsuitable to participate in this clinical trial

Sites / Locations

  • Memorial Sloan-Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fractionated Stem Cell Infusions

Arm Description

A single arm, open-label, single institution pilot trial is planned. Patients with chemosensitive MM and at least 7 x 10^6 CD34+ stem cells/kg (+/- 0.5 x 10^6 CD34+ stem cells/kg)available for use will be enrolled following initial induction or salvage therapy.

Outcomes

Primary Outcome Measures

engraftment kinetics
as measured by duration of neutropenia in patients with MM undergoing high-dose melphalan followed by fractionated CD34+ stem cell infusions.

Secondary Outcome Measures

safety and toxicity profile
of high-dose melphalan therapy followed by multiple doses of CD34+ stem cell rescue in patients with MM. Whenever possible, the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 should be used to describe the event and for assessing the severity of AEs.
neutrophil and platelet recovery rates.
Duration of neutropenia will be defined as the number of days ANC< 500x106/L. Time until platelet recovery (defined as platelets>=30x109/L), the number of units of red blood cells and platelets.
incidence of infection
The incidence of infection by three months after re-infusion will be calculated.
red cell and platelet transfusion requirements
will be evaluated using the Spearman rank correlation coefficient
duration of hospital admission
length of hospital stay in days will be summarized using descriptive statistics.
To assess symptom burden
using the MSK Modified M.D. Anderson Symptom Inventory (MDASI).
Multiple Myeloma response rates
at 3 months post-transplant according to standard response criteria. Response rates will be evaluated based on International Myeloma Working Group Uniform Response Criteria at 3 months following ASCT.
correlation between engraftment kinetics and symptom burden
in patients with MM who receive high-dose melphalan and fractionated CD34+ stem cell infusions
the number of CD34+ cells/Kg present
at the time of infusion. The difference between the number of CD34+ cells/kg given at each stem cell infusion time point and the number of CD34+ cells/kg before cryopreservation will be calculated as both a simple difference and percentage change.
To correlate the number CD34+ cells/Kg given
at the time of transplant with engraftment kinetics. The difference between the number of CD34+ cells/kg given at each stem cell infusion time point and the number of CD34+ cells/kg before cryopreservation will be calculated as both a simple difference and percentage change.

Full Information

First Posted
August 11, 2011
Last Updated
April 28, 2016
Sponsor
Memorial Sloan Kettering Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT01416246
Brief Title
Fractionated Stem Cell Infusions in Myeloma Patients Undergoing Autologous Stem Cell Transplant
Official Title
Pilot Trial of Fractionated Stem Cell Infusions in Myeloma Patients Undergoing Autologous Stem Cell Transplant
Study Type
Interventional

2. Study Status

Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
August 2011 (undefined)
Primary Completion Date
April 2016 (Actual)
Study Completion Date
April 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center

4. Oversight

5. Study Description

Brief Summary
Multiple myeloma is difficult to treat with only anti-cancer medicine (called chemotherapy) or radiation alone. Sometimes higher doses of chemotherapy are used but when used can also lower blood counts. Using own cells (special cells called stem cells) to help increase the blood counts after high doses of chemotherapy is called autologous stem cell transplantation (ASCT). Using own stem cells to restore blood counts and other advances in supportive measures (antibiotics and growth factors that increase blood counts) has improved the safety of ASCT. However, blood counts still decrease for a period of days after high doses of chemotherapy. During that time, patients are at greater risk for infections. Studies have shown that the faster the blood counts recover after ASCT, the less at risk there is for developing unwanted side effects after ASCT. Typically during an ASCT, a patient's stem cells are given back to them all at once on a single day. In this study, the investigators plan to see what happens when smaller amounts of own stem cells are given back to the patient over multiple days. The investigators want to find out what effects good and/or bad this will have on the patient and there multiple myeloma. Some studies have shown that giving back stem cells over a period of days helps to increase bone marrow activity and decrease the time it takes for blood counts to recover after ASCT. It is our hope that this new approach may lower a patient's risk of side effects and infections, decrease the number of blood transfusions that a patient needs during this process, reduce the time a patient has to spend in the hospital, and lower overall treatment costs.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Stem cell Infusions, Autologous Stem Cell Transplant, 11-105

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
26 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Fractionated Stem Cell Infusions
Arm Type
Experimental
Arm Description
A single arm, open-label, single institution pilot trial is planned. Patients with chemosensitive MM and at least 7 x 10^6 CD34+ stem cells/kg (+/- 0.5 x 10^6 CD34+ stem cells/kg)available for use will be enrolled following initial induction or salvage therapy.
Intervention Type
Procedure
Intervention Name(s)
Fractionated Stem Cell Infusions
Other Intervention Name(s)
Patients will receive standard supportive care measures (including, antimicrobial prophylaxis, red blood cell and platelet transfusions and, treatment for neutropenic fever) as per institutional practices. Neutrophil, engraftment is defined as absolute neutrophil count (ANC) > or = to 500 x 10^6/L for 2, consecutive days.
Intervention Description
Following enrollment patients will be treated with melphalan intravenously (IV) through a central venous catheter (CVC) over 30 minutes at 200mg/m2 or 140mg/m2 (if creatinine clearance is < or = to 50 and/or age > 70 years) on day -2. Following 24 hours of rest, the first dose of CD34+ stem cell will be administered on day 0 (2.5-5 x 106 CD 34+ stem cells/kg)+/- 0.5 x 106 CD34+ stem cells/kg), followed by 3 additional doses of CD 34+ stem cells (1.5-2.5 x 106 CD 34+ stem cells/kg)+/- 0.5 x 106 CD34+ stem cells/kg) on days +2, +4, and +6. Pegfilgrastim 6μg will be administered on day +1. Filgrastim 5μg/kg will be 12-24 hours after the 2nd-4th stem cell infusions. There will be a +/- 1 day window for the Day +2, +4, and +6 infusions to accommodate infusions that occur over the weekend or on holidays.
Primary Outcome Measure Information:
Title
engraftment kinetics
Description
as measured by duration of neutropenia in patients with MM undergoing high-dose melphalan followed by fractionated CD34+ stem cell infusions.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
safety and toxicity profile
Description
of high-dose melphalan therapy followed by multiple doses of CD34+ stem cell rescue in patients with MM. Whenever possible, the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 should be used to describe the event and for assessing the severity of AEs.
Time Frame
2 years
Title
neutrophil and platelet recovery rates.
Description
Duration of neutropenia will be defined as the number of days ANC< 500x106/L. Time until platelet recovery (defined as platelets>=30x109/L), the number of units of red blood cells and platelets.
Time Frame
2 years
Title
incidence of infection
Description
The incidence of infection by three months after re-infusion will be calculated.
Time Frame
3 months post-SCT
Title
red cell and platelet transfusion requirements
Description
will be evaluated using the Spearman rank correlation coefficient
Time Frame
2 years
Title
duration of hospital admission
Description
length of hospital stay in days will be summarized using descriptive statistics.
Time Frame
2 years
Title
To assess symptom burden
Description
using the MSK Modified M.D. Anderson Symptom Inventory (MDASI).
Time Frame
2 years
Title
Multiple Myeloma response rates
Description
at 3 months post-transplant according to standard response criteria. Response rates will be evaluated based on International Myeloma Working Group Uniform Response Criteria at 3 months following ASCT.
Time Frame
at 3 months
Title
correlation between engraftment kinetics and symptom burden
Description
in patients with MM who receive high-dose melphalan and fractionated CD34+ stem cell infusions
Time Frame
2 years
Title
the number of CD34+ cells/Kg present
Description
at the time of infusion. The difference between the number of CD34+ cells/kg given at each stem cell infusion time point and the number of CD34+ cells/kg before cryopreservation will be calculated as both a simple difference and percentage change.
Time Frame
2 years
Title
To correlate the number CD34+ cells/Kg given
Description
at the time of transplant with engraftment kinetics. The difference between the number of CD34+ cells/kg given at each stem cell infusion time point and the number of CD34+ cells/kg before cryopreservation will be calculated as both a simple difference and percentage change.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥18 and < than or = to 75 Histologic and serologic findings, reviewed at MSKCC, confirming the diagnosis of multiple myeloma. Standard diagnostic criteria for multiple myeloma will be used, as per the International Myeloma Foundation consensus guidelines (Durie et al, 2003) . Patients must have symptomatic multiple myeloma who have responded to prior induction or salvage chemotherapy (i.e. chemosensitive disease): Patients who are receiving high-dose melphalan and ASCT as part of their initial therapy require at least minor response to their last line of therapy to document chemosensitive disease (Anderson et al. 2008) Patients who are receiving high-dose melphalan and ASCT as part of salvage therapy require at least a minor response to their last line of therapy to document chemosensitive disease (Anderson et al. 2008). There is no limit on the number of prior regimens received by the patient. Patients must have at least 7 x 10^6 (+/- 0.5 x 10^6) CD34+ stem cells/kg frozen if he/she is being treated as part of a salvage (second) transplant strategy; patients must have 10 x 10^6 (+/- 0.5 x 10^6) CD34+ stem cells/kg frozen if ASCT is being performed as part of initial therapy. Adequate organ function is required, defined as follows: Serum bilirubin ≤ 2.0 mg/dl AST, ALT and alkaline phosphatase < 3 times the upper limit of laboratory normal Creatinine clearance > or = to 40 ml/min (24 hour urine collection or calculated*) *To be calculated by the Cockroft-Gault method: (140-Age) x Mass (kg) x [0.85 if female] (72 x Creatinine (mg/dL) LVEF > or = to 45% by MUGA or rest ECHO Diffusing capacity > or = to 45% (adjusted for hemoglobin) predicted by pulmonary function testing Performance status KPS > or = to 70%. Exclusion Criteria: Unstable angina or myocardial infarction within 4 months of initiating therapy on trial, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker Pregnant or lactating females Nonhematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas Contraindication to melphalan or any of the required supportive treatments, including hypersensitivity to G-CSF or pegfilgrastim Any other medical condition or laboratory evaluation that, in the treating physician's or principal investigator's opinion, makes the patient unsuitable to participate in this clinical trial
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Heather Landau, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mskcc.org/mskcc/html/44.cfm
Description
Memorial Sloan-Kettering Cancer Center

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Fractionated Stem Cell Infusions in Myeloma Patients Undergoing Autologous Stem Cell Transplant

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