Bendamustine Bridge to Autologous or Allogeneic Transplant for Relapsed/Refractory Lymphoma

Sponsor
Weill Medical College of Cornell University (Other)
Overall Status
Completed
CT.gov ID
NCT02059239
Collaborator
(none)
34
1
2
72.4
0.5

Study Details

Study Description

Brief Summary

This clinical trial is for men and women with whose lymphoma (non-Hodgkin or Hodgkin) did not respond to treatment or has returned after responding to previous therapy, and who are in need of a stem cell transplant.

The purpose of this study is to test the safety and effectiveness of giving the drug Bendamustine, followed by high dose chemotherapy, within two weeks prior to a stem cell transplant for lymphoma that has not achieved a complete response to salvage (treatment used for relapsed disease) chemotherapy.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

Subjects with Hodgkin's or Non-Hodgkin's lymphoma that did not respond to treatment or have disease that has returned after responding to previous treatment, and are in need of a stem cell transplant will be eligible for this pilot study. Thirty subjects will be enrolled, with 15 subjects assigned to the autologous transplant cohort (according to disease status and eligibility) and 15 subjects to the allogeneic transplant cohort (according to diseases status and eligibility).

Subjects will undergo the following a number of screening procedures to determine eligibility. All eligible subjects will receive bendamustine at a dose of 200 mg/ m2/ day for two days on Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Subjects will then receive the conditioning regimen, BEAM (carmustine, etoposide, cytarabine arabinoside, and Melphalan) and alemtuzumab for 6 days (Day -6 to Day -1) followed by an autologous or allogeneic transplant.

Subjects with pathological confirmed B-cell malignancies will also receive rituximab 375 mg/m2 on Days + 1 and +8 post-transplant. Subjects with T-cell lymphoma will be enrolled in the study but will not receive rituximab.

After the transplantation all subjects will receive medication to prevent graft vs host disease and supportive care to prevent infections. To speed up the recovery of stem cells, subjects will receive post-transplant filgrastim (G-CSF).

After discharge from the hospital, subjects will be seen regularly in the clinic for an exam and assessments. All these tests are considered standard of care.

Study Design

Study Type:
Interventional
Actual Enrollment :
34 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Pilot Study of a Sequential Regimen of Intensive Chemotherapy Followed by Autologous or Allogeneic Transplantation for Refractory Lymphoma (Non-Hodgkin's and Hodgkin's) and Phase 2 Expansion Cohort
Actual Study Start Date :
Jun 4, 2014
Actual Primary Completion Date :
Dec 16, 2019
Actual Study Completion Date :
Jun 15, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Chemo plus Autologous Transplantation

Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by autologous transplant

Drug: Bendamustine
Days - 24 and Day - 23 followed by a short break of 10 - 14 days.
Other Names:
  • Treanda
  • Drug: Carmustine
    300 mg/m2 on Day -6
    Other Names:
  • Bicnu
  • Drug: Etoposide
    100 mg/m2 on days -5 to -2
    Other Names:
  • Etopophos
  • Toposar
  • Drug: Melphalan
    140mg/m2 on Day -1
    Other Names:
  • Alkeran
  • Drug: Cytarabine
    200 mg/m2 on days -5 to -2
    Other Names:
  • Ara-C
  • Drug: Alemtuzumab
    20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors
    Other Names:
  • Campath
  • Biological: Autologous Stem Cell Transplantation

    Drug: Rituximab
    Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant
    Other Names:
  • Rituxan
  • Experimental: Chemo plus Allogeneic Transplantation

    Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by allogeneic transplant

    Drug: Bendamustine
    Days - 24 and Day - 23 followed by a short break of 10 - 14 days.
    Other Names:
  • Treanda
  • Drug: Carmustine
    300 mg/m2 on Day -6
    Other Names:
  • Bicnu
  • Drug: Etoposide
    100 mg/m2 on days -5 to -2
    Other Names:
  • Etopophos
  • Toposar
  • Drug: Melphalan
    140mg/m2 on Day -1
    Other Names:
  • Alkeran
  • Drug: Cytarabine
    200 mg/m2 on days -5 to -2
    Other Names:
  • Ara-C
  • Drug: Alemtuzumab
    20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors
    Other Names:
  • Campath
  • Biological: Allogeneic Stem Cell Transplantation

    Drug: Rituximab
    Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant
    Other Names:
  • Rituxan
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Patients Able to Proceed to Transplant [14 days after bendamustine treatment]

      Number of patients in each arm able to proceed to stem cell transplantation within 14 days of receiving bendamustine treatment

    2. Number of Patients Achieving Neutrophil Engraftment [35 Days Post-Transplant]

      Proportion of patients who successfully achieve neutrophil engraftment after stem cell transplant, defined as an absolute neutrophil count of 500/mm3 or for three consecutive days.

    3. Number of Patients Achieving Platelet Engraftment [74 Days Post-Transplant]

      Proportion of patients who successfully achieve platelet engraftment after stem cell transplant, defined as a platelet count of >20k/microL for three consecutive days without transfusion support for seven consecutive days.

    Secondary Outcome Measures

    1. Overall Survival at Day 100 Post-Transplant [From Day 0 until time of death, assessed up to 100 days post-transplant]

      The time from stem cell infusion (Day 0) to death from any cause.

    2. Overall Survival at Day 365 Post-Transplant [From Day 0 until time of death, assessed up to 365 days post-transplant]

      The time from stem cell infusion (Day 0) to death from any cause.

    3. Transplant-Related Mortality [From Day 0 until time of death, up to 100 days post-transplant.]

      Death due to any cause other than disease progression within first 100 days post-transplant.

    4. Disease Response Following Salvage Chemotherapy [Within 14 days of salvage chemotherapy treatment]

      Proportion of patients achieving a complete remission (CR; disappearance of clinically overt disease with no FDG-avid lesions on PET scan), partial remission (PR; reduction in clinical disease buden and >50% bi-dimensional decrease in tumor size on imaging), stable disease (SD; failure to meet the criteria for CR, PR or PD with no new areas of disease involvement) or progressive disease (PD; the appearance of any new lesion >1.5cm in size or a greater than 50% increase in the diameter of a previously identified node of over 1cm in size), as per Cheson Criteria, following salvage chemotherapy with Bendamustine.

    5. Disease Response 30 Days Post-Transplant [30 days after stem cell transplant]

      Proportion of patients achieving a complete remission (CR; disappearance of clinically overt disease with no FDG-avid lesions on PET scan), partial remission (PR; reduction in clinical disease buden and >50% bi-dimensional decrease in tumor size on imaging), stable disease (SD; failure to meet the criteria for CR, PR or PD with no new areas of disease involvement) or progressive disease (PD; the appearance of any new lesion >1.5cm in size or a greater than 50% increase in the diameter of a previously identified node of over 1cm in size), as per Cheson Criteria, 30 days following autologous or allogeneic stem cell transplant

    6. Disease Response at 1 Year Post-Transplant [1 year after stem cell transplant]

      Proportion of patients achieving a complete remission (CR; disappearance of clinically overt disease with no FDG-avid lesions on PET scan), partial remission (PR; reduction in clinical disease buden and >50% bi-dimensional decrease in tumor size on imaging), stable disease (SD; failure to meet the criteria for CR, PR or PD with no new areas of disease involvement) or progressive disease (PD; the appearance of any new lesion >1.5cm in size or a greater than 50% increase in the diameter of a previously identified node of over 1cm in size), as per Cheson Criteria, 1 year following autologous or allogeneic stem cell transplant

    7. Progression-Free Survival After Stem Cell Transplant [Stem cell transplant (Day 0) up to 2 years post-transplant]

      Time elapsed between stem cell transplant (Day 0) and disease progression, as defined by the Cheson Criteria (the appearance of any new lesion >1.5cm in size or a greater than 50% increase in the diameter of a previously identified node of over 1cm in size)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • must have histologically or cytologically confirmed relapsed or primary refractory lymphoma (including Hodgkin's Lymphoma) staged with Positron Emission Tomography (PET) scan to have

    • Allogeneic arm:

    • Progressive disease or

    • No response to salvage therapy or

    • Partial response to salvage therapy defined as > 50% reduction in bidirectional area of masses but standardized uptake value (SUV) remains ≥8 in at least some PET avid areas

    • Prior autologous transplant

    • Autologous arm:

    • Partial response of >50% reduction in bidirectional area of masses and SUV reduction to <8 in PET avid areas Subjects must have evaluable disease.

    • Subjects must have received at least one induction therapy and one line of salvage therapy that each incorporate at least two drugs that are standard of care for lymphoma

    • Age >18 years.

    • Karnofsky Performance Score (KPS) ≥ 50%

    • For autologous transplants: Subjects must have an adequate number of CD34+ stem cells collected to allow for transplantation. This number is defined as ≥ 2x106 CD34+ cells / kg body weight. If not previously collected and stored, the subject must be willing to undergo stem cell mobilization and collection as per standard practice. If sufficient cells cannot be collected, subjects will be offered the option to proceed with the allogeneic arm of the study.

    • Male and female subjects must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment. Female subjects of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment.

    • Ability to understand and the willingness to sign a written informed consent document.

    Exclusion Criteria:
    • Known to be positive for HIV

    • Subjects may not be receiving any other investigational agents (defined as non FDA-approved agents) at the time of initiating bendamustine regimen. However, the salvage therapy for lymphoma can be part of an ongoing clinical trial with an investigational agent.

    • Women who are pregnant or breast feeding. Women of childbearing age must use adequate contraception and have a negative pregnancy test.

    • The risks to an unborn fetus or potential risks in nursing infants are unknown.

    • History of allergic reactions attributed to compounds of similar chemical or biologic composition to any medications listed in the protocol.

    • Subject with severely decreased Left Ventricular Ejection Fraction (LVEF) or severely impaired pulmonary function tests (PFT's)

    • Uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Weill Cornell Medical College New York New York United States 10065

    Sponsors and Collaborators

    • Weill Medical College of Cornell University

    Investigators

    • Principal Investigator: Tsiporah Shore, MD, Weill Medical College of Cornell University

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Weill Medical College of Cornell University
    ClinicalTrials.gov Identifier:
    NCT02059239
    Other Study ID Numbers:
    • 1208012875
    First Posted:
    Feb 11, 2014
    Last Update Posted:
    Feb 21, 2021
    Last Verified:
    Feb 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Weill Medical College of Cornell University
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Chemo Plus Autologous Transplantation Chemo Plus Allogeneic Transplantation
    Arm/Group Description Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by autologous transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Autologous Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by allogeneic transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Allogeneic Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant
    Period Title: Overall Study
    STARTED 18 16
    COMPLETED 16 13
    NOT COMPLETED 2 3

    Baseline Characteristics

    Arm/Group Title Chemo Plus Autologous Transplantation Chemo Plus Allogeneic Transplantation Total
    Arm/Group Description Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by autologous transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Autologous Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by allogeneic transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Allogeneic Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant Total of all reporting groups
    Overall Participants 18 16 34
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    14
    77.8%
    13
    81.3%
    27
    79.4%
    >=65 years
    4
    22.2%
    3
    18.8%
    7
    20.6%
    Sex: Female, Male (Count of Participants)
    Female
    6
    33.3%
    7
    43.8%
    13
    38.2%
    Male
    12
    66.7%
    9
    56.3%
    21
    61.8%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    2
    11.1%
    0
    0%
    2
    5.9%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    1
    5.6%
    2
    12.5%
    3
    8.8%
    White
    14
    77.8%
    12
    75%
    26
    76.5%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    1
    5.6%
    2
    12.5%
    3
    8.8%
    Region of Enrollment (participants) [Number]
    United States
    18
    100%
    16
    100%
    34
    100%
    Diagnosis (Count of Participants)
    Diffuse Large B-Cell Lymphoma
    6
    33.3%
    1
    6.3%
    7
    20.6%
    Follicular Lymphoma
    2
    11.1%
    1
    6.3%
    3
    8.8%
    Hodgkin's Disease
    5
    27.8%
    3
    18.8%
    8
    23.5%
    Mantle Cell Lymphoma
    2
    11.1%
    1
    6.3%
    3
    8.8%
    Transformed Diffuse Large B-Cell Lymphoma
    2
    11.1%
    4
    25%
    6
    17.6%
    Peripheral T-Cell Lymphoma
    0
    0%
    2
    12.5%
    2
    5.9%
    Other
    1
    5.6%
    4
    25%
    5
    14.7%
    Lines of Prior Therapy (Lines of Therapy) [Number]
    2 Lines
    11
    3
    14
    3 Lines
    4
    3
    7
    4 Lines
    1
    5
    6
    5+ Lines
    2
    5
    7

    Outcome Measures

    1. Primary Outcome
    Title Number of Patients Able to Proceed to Transplant
    Description Number of patients in each arm able to proceed to stem cell transplantation within 14 days of receiving bendamustine treatment
    Time Frame 14 days after bendamustine treatment

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Chemo Plus Autologous Transplantation Chemo Plus Allogeneic Transplantation
    Arm/Group Description Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by autologous transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Autologous Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by allogeneic transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Allogeneic Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant
    Measure Participants 18 16
    Proceeded to Transplant
    16
    88.9%
    13
    81.3%
    Did Not Proceed to Transplant - Physician Decision
    1
    5.6%
    0
    0%
    Did Not Proceed to Transplant - Progressive Disease
    1
    5.6%
    3
    18.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Chemo Plus Autologous Transplantation
    Comments
    Type of Statistical Test Other
    Comments Simple proportion in autologous group with exact (Clopper-Pearson) 95% confidence interval.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Proportion (percent)
    Estimated Value 88.9
    Confidence Interval (2-Sided) 95%
    65.3 to 98.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Chemo Plus Allogeneic Transplantation
    Comments
    Type of Statistical Test Other
    Comments Simple proportion in allogeneic group with exact (Clopper-Pearson) 95% confidence interval.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Proportion (percent)
    Estimated Value 81.3
    Confidence Interval (2-Sided) 95%
    54.4 to 95.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Primary Outcome
    Title Number of Patients Achieving Neutrophil Engraftment
    Description Proportion of patients who successfully achieve neutrophil engraftment after stem cell transplant, defined as an absolute neutrophil count of 500/mm3 or for three consecutive days.
    Time Frame 35 Days Post-Transplant

    Outcome Measure Data

    Analysis Population Description
    5 participants (2 from chemo + autologous transplant arm, 3 from chemo + allogeneic transplant arm) were unable to be analyzed for this outcome measure as they did not complete the study and did not receive an autologous or allogeneic transplant.
    Arm/Group Title Chemo Plus Autologous Transplantation Chemo Plus Allogeneic Transplantation
    Arm/Group Description Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by autologous transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Autologous Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by allogeneic transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Allogeneic Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant
    Measure Participants 16 13
    Count of Participants [Participants]
    16
    88.9%
    13
    81.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Chemo Plus Autologous Transplantation
    Comments
    Type of Statistical Test Other
    Comments Simple proportion in autologous group with exact (Clopper-Pearson) 95% confidence interval.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Proportion (percent)
    Estimated Value 100.0
    Confidence Interval (2-Sided) 95%
    79.4 to 100.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Chemo Plus Allogeneic Transplantation
    Comments
    Type of Statistical Test Other
    Comments Simple proportion in allogeneic group with exact (Clopper-Pearson) 95% confidence interval.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Proportion (percent)
    Estimated Value 100.0
    Confidence Interval (2-Sided) 95%
    75.3 to 100.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Primary Outcome
    Title Number of Patients Achieving Platelet Engraftment
    Description Proportion of patients who successfully achieve platelet engraftment after stem cell transplant, defined as a platelet count of >20k/microL for three consecutive days without transfusion support for seven consecutive days.
    Time Frame 74 Days Post-Transplant

    Outcome Measure Data

    Analysis Population Description
    5 participants (2 from chemo + autologous transplant arm, 3 from chemo + allogeneic transplant arm) were unable to be analyzed for this outcome measure as they did not complete the study and did not receive an autologous or allogeneic transplant.
    Arm/Group Title Chemo Plus Autologous Transplantation Chemo Plus Allogeneic Transplantation
    Arm/Group Description Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by autologous transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Autologous Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by allogeneic transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Allogeneic Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant
    Measure Participants 16 13
    Count of Participants [Participants]
    16
    88.9%
    12
    75%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Chemo Plus Autologous Transplantation
    Comments
    Type of Statistical Test Other
    Comments Simple proportion in autologous group with exact (Clopper-Pearson) 95% confidence interval.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Proportion (percent)
    Estimated Value 100.0
    Confidence Interval (2-Sided) 95%
    79.4 to 100.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Chemo Plus Allogeneic Transplantation
    Comments
    Type of Statistical Test Other
    Comments Simple proportion in allogeneic group with exact (Clopper-Pearson) 95% confidence interval.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Proportion (percent)
    Estimated Value 92.3
    Confidence Interval (2-Sided) 95%
    64.0 to 99.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Overall Survival at Day 100 Post-Transplant
    Description The time from stem cell infusion (Day 0) to death from any cause.
    Time Frame From Day 0 until time of death, assessed up to 100 days post-transplant

    Outcome Measure Data

    Analysis Population Description
    5 participants (2 from chemo + autologous transplant arm, 3 from chemo + allogeneic transplant arm) were unable to be analyzed for this outcome measure as they did not complete the study and did not receive an autologous or allogeneic transplant.
    Arm/Group Title Chemo Plus Autologous Transplantation Chemo Plus Allogeneic Transplantation
    Arm/Group Description Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by autologous transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Autologous Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by allogeneic transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Allogeneic Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant
    Measure Participants 16 13
    Alive
    16
    88.9%
    11
    68.8%
    Deceased
    0
    0%
    2
    12.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Chemo Plus Autologous Transplantation
    Comments
    Type of Statistical Test Other
    Comments Simple proportion in autologous group with exact (Clopper-Pearson) 95% confidence interval.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Proportion (percent)
    Estimated Value 100.0
    Confidence Interval (2-Sided) 95%
    79.4 to 100.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Chemo Plus Allogeneic Transplantation
    Comments
    Type of Statistical Test Other
    Comments Simple proportion in allogeneic group with exact (Clopper-Pearson) 95% confidence interval.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Proportion (percent)
    Estimated Value 84.6
    Confidence Interval (2-Sided) 95%
    54.6 to 98.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Overall Survival at Day 365 Post-Transplant
    Description The time from stem cell infusion (Day 0) to death from any cause.
    Time Frame From Day 0 until time of death, assessed up to 365 days post-transplant

    Outcome Measure Data

    Analysis Population Description
    5 participants (2 from chemo + autologous transplant arm, 3 from chemo + allogeneic transplant arm) were unable to be analyzed for this outcome measure as they did not complete the study and did not receive an autologous or allogeneic transplant.
    Arm/Group Title Chemo Plus Autologous Transplantation Chemo Plus Allogeneic Transplantation
    Arm/Group Description Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by autologous transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Autologous Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by allogeneic transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Allogeneic Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant
    Measure Participants 16 13
    Alive
    16
    88.9%
    6
    37.5%
    Deceased
    0
    0%
    7
    43.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Chemo Plus Autologous Transplantation
    Comments
    Type of Statistical Test Other
    Comments Simple proportion in autologous group with exact (Clopper-Pearson) 95% confidence interval.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Proportion (percent)
    Estimated Value 100.0
    Confidence Interval (2-Sided) 95%
    79.4 to 100.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Chemo Plus Allogeneic Transplantation
    Comments
    Type of Statistical Test Other
    Comments Simple proportion in allogeneic group with exact (Clopper-Pearson) 95% confidence interval.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Proportion (percent)
    Estimated Value 46.2
    Confidence Interval (2-Sided) 95%
    19.2 to 74.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Transplant-Related Mortality
    Description Death due to any cause other than disease progression within first 100 days post-transplant.
    Time Frame From Day 0 until time of death, up to 100 days post-transplant.

    Outcome Measure Data

    Analysis Population Description
    5 participants (2 from chemo + autologous transplant arm, 3 from chemo + allogeneic transplant arm) were unable to be analyzed for this outcome measure as they did not complete the study and did not receive an autologous or allogeneic transplant.
    Arm/Group Title Chemo Plus Autologous Transplantation Chemo Plus Allogeneic Transplantation
    Arm/Group Description Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by autologous transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Autologous Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by allogeneic transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Allogeneic Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant
    Measure Participants 16 13
    Count of Participants [Participants]
    0
    0%
    2
    12.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Chemo Plus Autologous Transplantation
    Comments
    Type of Statistical Test Other
    Comments Simple proportion in autologous group with exact (Clopper-Pearson) 95% confidence interval.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Proportion (percent)
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    0.0 to 20.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Chemo Plus Allogeneic Transplantation
    Comments
    Type of Statistical Test Other
    Comments Simple proportion in allogeneic group with exact (Clopper-Pearson) 95% confidence interval.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Proportion (percent)
    Estimated Value 15.4
    Confidence Interval (2-Sided) 95%
    1.9 to 45.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Disease Response Following Salvage Chemotherapy
    Description Proportion of patients achieving a complete remission (CR; disappearance of clinically overt disease with no FDG-avid lesions on PET scan), partial remission (PR; reduction in clinical disease buden and >50% bi-dimensional decrease in tumor size on imaging), stable disease (SD; failure to meet the criteria for CR, PR or PD with no new areas of disease involvement) or progressive disease (PD; the appearance of any new lesion >1.5cm in size or a greater than 50% increase in the diameter of a previously identified node of over 1cm in size), as per Cheson Criteria, following salvage chemotherapy with Bendamustine.
    Time Frame Within 14 days of salvage chemotherapy treatment

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Chemo Plus Autologous Transplantation Chemo Plus Allogeneic Transplantation
    Arm/Group Description Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by autologous transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Autologous Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by allogeneic transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Allogeneic Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant
    Measure Participants 18 16
    Complete Remission
    4
    22.2%
    1
    6.3%
    Partial Remission
    8
    44.4%
    6
    37.5%
    Stable Disease
    4
    22.2%
    2
    12.5%
    Progressive Disease
    1
    5.6%
    6
    37.5%
    Not Assessed
    1
    5.6%
    1
    6.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Chemo Plus Autologous Transplantation
    Comments
    Type of Statistical Test Other
    Comments Simple proportion (objective response: CR+PR) in autologous group with exact (Clopper-Pearson) 95% confidence interval.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Proportion (percent)
    Estimated Value 66.7
    Confidence Interval (2-Sided) 95%
    41.0 to 86.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Chemo Plus Allogeneic Transplantation
    Comments
    Type of Statistical Test Other
    Comments Simple proportion (objective response: CR+PR) in allogeneic group with exact (Clopper-Pearson) 95% confidence interval.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Proportion (percent)
    Estimated Value 43.8
    Confidence Interval (2-Sided) 95%
    19.8 to 70.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Disease Response 30 Days Post-Transplant
    Description Proportion of patients achieving a complete remission (CR; disappearance of clinically overt disease with no FDG-avid lesions on PET scan), partial remission (PR; reduction in clinical disease buden and >50% bi-dimensional decrease in tumor size on imaging), stable disease (SD; failure to meet the criteria for CR, PR or PD with no new areas of disease involvement) or progressive disease (PD; the appearance of any new lesion >1.5cm in size or a greater than 50% increase in the diameter of a previously identified node of over 1cm in size), as per Cheson Criteria, 30 days following autologous or allogeneic stem cell transplant
    Time Frame 30 days after stem cell transplant

    Outcome Measure Data

    Analysis Population Description
    5 participants (2 from chemo + autologous transplant arm, 3 from chemo + allogeneic transplant arm) were unable to be analyzed for this outcome measure as they did not complete the study and did not receive an autologous or allogeneic transplant.
    Arm/Group Title Chemo Plus Autologous Transplantation Chemo Plus Allogeneic Transplantation
    Arm/Group Description Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by autologous transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Autologous Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by allogeneic transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Allogeneic Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant
    Measure Participants 16 13
    Complete Remission
    12
    66.7%
    7
    43.8%
    Partial Remission
    2
    11.1%
    3
    18.8%
    Stable Disease
    2
    11.1%
    1
    6.3%
    Progressive Disease
    0
    0%
    1
    6.3%
    Not Assessed
    0
    0%
    1
    6.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Chemo Plus Autologous Transplantation
    Comments
    Type of Statistical Test Other
    Comments Simple proportion (objective response: CR+PR) in autologous group with exact (Clopper-Pearson) 95% confidence interval.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Proportion (percent)
    Estimated Value 87.5
    Confidence Interval (2-Sided) 95%
    61.7 to 98.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Chemo Plus Allogeneic Transplantation
    Comments
    Type of Statistical Test Other
    Comments Simple proportion (objective response: CR+PR) in allogeneic group with exact (Clopper-Pearson) 95% confidence interval.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Proportion (percent)
    Estimated Value 76.9
    Confidence Interval (2-Sided) 95%
    46.2 to 95.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Disease Response at 1 Year Post-Transplant
    Description Proportion of patients achieving a complete remission (CR; disappearance of clinically overt disease with no FDG-avid lesions on PET scan), partial remission (PR; reduction in clinical disease buden and >50% bi-dimensional decrease in tumor size on imaging), stable disease (SD; failure to meet the criteria for CR, PR or PD with no new areas of disease involvement) or progressive disease (PD; the appearance of any new lesion >1.5cm in size or a greater than 50% increase in the diameter of a previously identified node of over 1cm in size), as per Cheson Criteria, 1 year following autologous or allogeneic stem cell transplant
    Time Frame 1 year after stem cell transplant

    Outcome Measure Data

    Analysis Population Description
    5 participants (2 from chemo + autologous transplant arm, 3 from chemo + allogeneic transplant arm) were unable to be analyzed for this outcome measure as they did not complete the study and did not receive an autologous or allogeneic transplant.
    Arm/Group Title Chemo Plus Autologous Transplantation Chemo Plus Allogeneic Transplantation
    Arm/Group Description Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by autologous transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Autologous Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by allogeneic transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Allogeneic Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant
    Measure Participants 16 13
    Complete Remission
    12
    66.7%
    4
    25%
    Partial Remission
    1
    5.6%
    0
    0%
    Stable Disease
    0
    0%
    0
    0%
    Progressive Disease
    3
    16.7%
    2
    12.5%
    Not Assessed
    0
    0%
    0
    0%
    Patient Deceased
    0
    0%
    7
    43.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Chemo Plus Autologous Transplantation
    Comments
    Type of Statistical Test Other
    Comments Simple proportion (objective response: CR+PR) in autologous group with exact (Clopper-Pearson) 95% confidence interval.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Proportion (percent)
    Estimated Value 81.3
    Confidence Interval (2-Sided) 95%
    54.4 to 96.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Chemo Plus Allogeneic Transplantation
    Comments
    Type of Statistical Test Other
    Comments Simple proportion (objective response: CR+PR) in allogeneic group with exact (Clopper-Pearson) 95% confidence interval.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Proportion (percent)
    Estimated Value 30.8
    Confidence Interval (2-Sided) 95%
    9.1 to 61.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    10. Secondary Outcome
    Title Progression-Free Survival After Stem Cell Transplant
    Description Time elapsed between stem cell transplant (Day 0) and disease progression, as defined by the Cheson Criteria (the appearance of any new lesion >1.5cm in size or a greater than 50% increase in the diameter of a previously identified node of over 1cm in size)
    Time Frame Stem cell transplant (Day 0) up to 2 years post-transplant

    Outcome Measure Data

    Analysis Population Description
    5 participants (2 from chemo + autologous transplant arm, 3 from chemo + allogeneic transplant arm) were unable to be analyzed for this outcome measure as they did not complete the study and did not receive an autologous or allogeneic transplant.
    Arm/Group Title Chemo Plus Autologous Transplantation Chemo Plus Allogeneic Transplantation
    Arm/Group Description Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by autologous transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Autologous Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by allogeneic transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Allogeneic Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant
    Measure Participants 16 13
    Median (95% Confidence Interval) [Months]
    NA
    8
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Chemo Plus Allogeneic Transplantation
    Comments
    Type of Statistical Test Other
    Comments Median PFS in allogeneic group with exact (Clopper-Pearson) 95% confidence interval.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Median (95% CI)
    Estimated Value 8
    Confidence Interval (2-Sided) 95%
    5 to 25
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame Adverse events were assessed Day -24 (start of Bendamustine treatment) through 1 year post-transplant.
    Adverse Event Reporting Description All adverse events were first documented by the study transplant physicians and thereafter collated and graded by two independent reviewed according to CTCAE version 4.0. 5 participants (2 autologous, 3 allogeneic) did not proceed to transplant and were not evaluable for adverse events on the Chemo Plus Autologous Transplant or Chemo Plus Allogeneic Transplant arms.
    Arm/Group Title Bendamustine Bendamustine Plus Autologous Transplantation Bendamustine Plus Allogeneic Transplantation
    Arm/Group Description Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by autologous transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Autologous Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by allogeneic transplant Bendamustine: Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Carmustine: 300 mg/m2 on Day -6 Etoposide: 100 mg/m2 on days -5 to -2 Melphalan: 140mg/m2 on Day -1 Cytarabine: 200 mg/m2 on days -5 to -2 Alemtuzumab: 20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors Allogeneic Stem Cell Transplantation Rituximab: Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant
    All Cause Mortality
    Bendamustine Bendamustine Plus Autologous Transplantation Bendamustine Plus Allogeneic Transplantation
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/34 (0%) 0/16 (0%) 7/13 (53.8%)
    Serious Adverse Events
    Bendamustine Bendamustine Plus Autologous Transplantation Bendamustine Plus Allogeneic Transplantation
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/34 (5.9%) 4/16 (25%) 10/13 (76.9%)
    Blood and lymphatic system disorders
    Myelodysplastic Syndrome 0/34 (0%) 0 1/16 (6.3%) 1 0/13 (0%) 0
    Acute Myeloid Leukemia 0/34 (0%) 0 1/16 (6.3%) 1 0/13 (0%) 0
    Cardiac disorders
    Pericardial Effusion 0/34 (0%) 0 0/16 (0%) 0 1/13 (7.7%) 1
    Heart Failure 1/34 (2.9%) 1 0/16 (0%) 0 1/13 (7.7%) 1
    Gastrointestinal disorders
    Lower Gastrointestinal Hemorrhage 0/34 (0%) 0 0/16 (0%) 0 2/13 (15.4%) 2
    Intestinal Necrosis 0/34 (0%) 0 0/16 (0%) 0 1/13 (7.7%) 1
    Infections and infestations
    Disseminated Adenovirus Infection 0/34 (0%) 0 0/16 (0%) 0 1/13 (7.7%) 1
    Sepsis 0/34 (0%) 0 0/16 (0%) 0 2/13 (15.4%) 2
    Investigations
    Post-Transplant Lymphoproliferative Disorder 0/34 (0%) 0 0/16 (0%) 0 2/13 (15.4%) 2
    Chronic Graft versus Host Disease 0/34 (0%) 0 0/16 (0%) 0 1/13 (7.7%) 1
    Respiratory, thoracic and mediastinal disorders
    Pulmonary Hypertension 1/34 (2.9%) 1 0/16 (0%) 0 0/13 (0%) 0
    Acute Respiratory Distress 0/34 (0%) 0 1/16 (6.3%) 1 3/13 (23.1%) 3
    Acute Respiratory Failure 0/34 (0%) 0 1/16 (6.3%) 1 4/13 (30.8%) 4
    Vascular disorders
    Hypotension 0/34 (0%) 0 0/16 (0%) 0 1/13 (7.7%) 1
    Other (Not Including Serious) Adverse Events
    Bendamustine Bendamustine Plus Autologous Transplantation Bendamustine Plus Allogeneic Transplantation
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 9/34 (26.5%) 16/16 (100%) 13/13 (100%)
    Blood and lymphatic system disorders
    Febrile Neutropenia 2/34 (5.9%) 2 11/16 (68.8%) 11 2/13 (15.4%) 2
    Hemolysis 0/34 (0%) 0 0/16 (0%) 0 1/13 (7.7%) 1
    Cardiac disorders
    Paroxysmal Atrial Tachycardia 1/34 (2.9%) 1 0/16 (0%) 0 0/13 (0%) 0
    Gastrointestinal disorders
    Diarrhea 1/34 (2.9%) 1 0/16 (0%) 0 7/13 (53.8%) 7
    Oral Mucositis 0/34 (0%) 0 2/16 (12.5%) 2 5/13 (38.5%) 5
    Nausea 0/34 (0%) 0 0/16 (0%) 0 4/13 (30.8%) 4
    General disorders
    Fever 1/34 (2.9%) 1 0/16 (0%) 0 0/13 (0%) 0
    Hepatobiliary disorders
    Hyperbilirubinemia 0/34 (0%) 0 0/16 (0%) 0 3/13 (23.1%) 3
    Infections and infestations
    Cytomegalovirus Viremia 0/34 (0%) 0 0/16 (0%) 0 4/13 (30.8%) 4
    Epstein-Barr Virus Viremia 0/34 (0%) 0 0/16 (0%) 0 2/13 (15.4%) 2
    Urinary Tract Infection 0/34 (0%) 0 0/16 (0%) 0 2/13 (15.4%) 2
    Soft Tissue Infection 0/34 (0%) 0 0/16 (0%) 0 3/13 (23.1%) 3
    Lung Infection - Pneumonia 0/34 (0%) 0 0/16 (0%) 0 3/13 (23.1%) 3
    Lung Infection - Viral Pneumonia 0/34 (0%) 0 0/16 (0%) 0 1/13 (7.7%) 1
    Lung Infection - Fungal Pneumonia 0/34 (0%) 0 0/16 (0%) 0 2/13 (15.4%) 2
    Bacteremia 0/34 (0%) 0 1/16 (6.3%) 1 13/13 (100%) 14
    Clostridium difficile colitis 0/34 (0%) 0 1/16 (6.3%) 1 0/13 (0%) 0
    Norovirus Enterocolitis 0/34 (0%) 0 1/16 (6.3%) 1 0/13 (0%) 0
    Upper Respiratory Infection - Influenza A 0/34 (0%) 0 1/16 (6.3%) 1 0/13 (0%) 0
    Upper Respiratory Infection - Rhinovirus 0/34 (0%) 0 2/16 (12.5%) 2 0/13 (0%) 0
    Upper Respiratory Infection - Respiratory Syncytial Virus 0/34 (0%) 0 1/16 (6.3%) 1 0/13 (0%) 0
    Metabolism and nutrition disorders
    Hypocalcemia 1/34 (2.9%) 1 0/16 (0%) 0 0/13 (0%) 0
    Tumor Lysis Syndrome 1/34 (2.9%) 1 0/16 (0%) 0 0/13 (0%) 0
    Anorexia 0/34 (0%) 0 0/16 (0%) 0 9/13 (69.2%) 9
    Hyperkalemia 0/34 (0%) 0 0/16 (0%) 0 1/13 (7.7%) 1
    Hypokalemia 0/34 (0%) 0 2/16 (12.5%) 2 3/13 (23.1%) 3
    Hypoalbuminemia 0/34 (0%) 0 0/16 (0%) 0 4/13 (30.8%) 4
    Musculoskeletal and connective tissue disorders
    Generalized Muscle Weakness 0/34 (0%) 0 0/16 (0%) 0 2/13 (15.4%) 2
    Nervous system disorders
    Headache 1/34 (2.9%) 1 0/16 (0%) 0 0/13 (0%) 0
    Syncope 1/34 (2.9%) 1 0/16 (0%) 0 0/13 (0%) 0
    Intracranial Hemorrhage 0/34 (0%) 0 0/16 (0%) 0 1/13 (7.7%) 1
    Psychiatric disorders
    Delirium 0/34 (0%) 0 0/16 (0%) 0 2/13 (15.4%) 2
    Renal and urinary disorders
    Acute Renal Failure 0/34 (0%) 0 0/16 (0%) 0 2/13 (15.4%) 2
    Respiratory, thoracic and mediastinal disorders
    Hypoxia 1/34 (2.9%) 1 0/16 (0%) 0 2/13 (15.4%) 2
    Pulmonary Edema 0/34 (0%) 0 0/16 (0%) 0 2/13 (15.4%) 2
    Skin and subcutaneous tissue disorders
    Maculopapular Rash 0/34 (0%) 0 0/16 (0%) 0 2/13 (15.4%) 2

    Limitations/Caveats

    [Not Specified]

    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.

    Results Point of Contact

    Name/Title Dr. Tsiporah Shore
    Organization Weill Cornell Medicine
    Phone 646-962-7950
    Email tbs2001@med.cornell.edu
    Responsible Party:
    Weill Medical College of Cornell University
    ClinicalTrials.gov Identifier:
    NCT02059239
    Other Study ID Numbers:
    • 1208012875
    First Posted:
    Feb 11, 2014
    Last Update Posted:
    Feb 21, 2021
    Last Verified:
    Feb 1, 2021