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Study of Low-Intensity Conditioning for Allogeneic Stem Cell Transplant

Primary Purpose

Multiple Myeloma, Lymphocytic Leukemia, Chronic, Lymphoma, Low-Grade

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Reduced intensity conditioning
Rapid immunosuppressive taper
Prophylactic donor leukocyte infusions
Sponsored by
University of Michigan Rogel Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Patient Inclusion Criteria: To be eligible a patient MUST meet at least one of the next 4 criteria Any patient aged 55 years or older with a hematological malignancy for which allogeneic transplant is considered an appropriate treatment, AND/OR Any patient, regardless of age, with a hematologic malignancy for which allogeneic transplant is considered an appropriate treatment and the patient is not eligible for a conventional myeloablative transplant because of organ dysfunction AND/OR Any patient, regardless of age, who has relapsed following prior autologous or allogeneic transplant for a hematologic malignancy AND/OR Any patient, regardless of age, with one of the following hematological malignancies: Multiple myeloma refractory to or failure following conventional chemotherapy such as VAD (Vincristine, Adriamycin and Dexamethasone), pulse decadron, or alkylating agents, or chromosomal abnormality associated with poor prognosis by cytogenetics or FISH probe. Chronic lymphocytic leukemia patients, Rai stage 3 or 4 and relapsed following/refractory to alkylating agents or nucleoside analog therapy Low grade lymphoma (small lymphocytic, follicular small cleaved cell, or follicular mixed small cleaved and large cell) that is either relapsed or refractory provided the disease is NOT rapidly progressive, NOT bulky, and no mass exceeds 5 cm in greatest dimension. To be eligible a patient MUST meet all of the following criteria In addition to the above criteria ALL patients must meet the following minimum organ function: Cardiac: Ejection fraction at least 30%. Renal: Adequate renal function as defined by creatinine < 2.0mg OR creatinine clearance >40 mg/min by 24-hour urine collection or GFR (Glomerular Filtration Rate. (Gender and age-adjusted creatinine clearance >40ml/min by Gault-Cockroft 55 is acceptable for adults: (140 - age) x weight/72 x Scr [x 0.85 if female]). Pulmonary: FEV1 and FVC >60%. Hepatic: Total bilirubin <2.0 and AST (Aspartate Aminotransferase)/ALT (Alanine Transaminase) < 3X institutional normal for age. Performance (adults): Karnofsky score must be at least 60; for pts. under 16, Lansky score must be at least 60. Availability of a 5/6 or 6/6 HLA A, B, and DR identical relative who is willing and able to donate allogeneic stem cells. Serological, low resolution or mid resolution molecular typing will determine the degree of match for HLA (Human Leukocyte Antigen) class I regardless of high resolution DNA typing results. High resolution typing will be used to determine the degree of match for HLA-DR. No untreated or uncontrolled invasive infections. Patients still under therapy for presumed or proven infection are eligible provided there is clear evidence (radiologic and/or culture) that the infection is well controlled. Patients under treatment for infection will be enrolled only after clearance from the Principal Investigator. Not pregnant Patient Exclusion Criteria: acute leukemia HIV positive patients not eligible Any physical or psychological condition that, in the opinion of the investigator, would pose unacceptable risk to the patient Pregnant Donor Inclusion Criteria: 5/6 or 6/6 HLA match for HLA-A, B, and DR Age 3-70 years, good general health No contraindication to G-CSF (Granulocyte Colony-Stimulating Factor)stimulation No contraindication to leukapheresis of peripheral blood stem cells Good general health Donor Exclusion Criteria: HIV positive or history of HIV risk factors Presence of other diseases transmissible by blood that pose unacceptable risk to the study subject. Pregnant Medical or psychological conditions that would make the donor unlikely to tolerate G-CSF - injections or leukapheresis

Sites / Locations

  • The University of Michigan

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Immunosuppression Taper

Arm Description

Reduced intensity conditioning consisting of Busulfan and Fludarabine(fludarabine 150 mg/m2 IV, busulfan 6 mg/kg IV, total lymphoid irradiation 2 Gy), followed by a rapid immunosuppressive taper of Tacrolimus (0.06 mg/kg q12h, PO, Days -7 to +28), Methotrexate (5 mg/m2, IV, Days +1, +3, +6, +11) and Mycophenolate Mofetil (10 mg/kg every 8 hours, PO, Days -6 to +7).

Outcomes

Primary Outcome Measures

Percentage of Participants With Acute Graft Versus Host Disease (GVHD) Grades 2-4
The primary objective of this study was to establish the rate of acute GVHD following prophylactic cellular immunotherapy after allogeneic hematopoietic stem cell therapy using low intensity conditioning for high-risk hematological malignancies. Glucksberg staging was used for organ grading of GVHD. Clinical GVHD was assessed as follows: Grade 0: No stage 1-4 of any organ Grade 1: Stage 1-2 rash and no liver or gut involvement Grade 2: Stage 3 rash, or Stage 1 liver involvement, or Stage 1 GI Grade 3: Stage 0-3 skin with Stage 2-3 liver, or Stage 2-4 GI Grade 4: Stage 4 skin rash, or Stage 4 liver involvement
Percentage of Participants With Progression Free Survival
The second primary objective was to determine the percentage of participants with progression free survival following prophylactic cellular immunotherapy after allogeneic hematopoietic stem cell therapy using low intensity conditioning for high-risk hematological malignancies. We define disease progression as disease recurrence within 180 days of transplant.

Secondary Outcome Measures

Percentage of Patients Alive at 2 Years
To estimate the overall survival of patients progression following prophylactic cellular immunotherapy after allogeneic hematopoietic stem cell therapy using low intensity conditioning for high-risk hematological malignancies.

Full Information

First Posted
August 31, 2005
Last Updated
January 18, 2017
Sponsor
University of Michigan Rogel Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT00143845
Brief Title
Study of Low-Intensity Conditioning for Allogeneic Stem Cell Transplant
Official Title
Phase II Trial of Adjuvant Cellular Immunotherapy for High-Risk Hematologic Malignancy After Reduced Intensity Allogeneic Stem Cell Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
April 2003 (undefined)
Primary Completion Date
November 2010 (Actual)
Study Completion Date
February 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Michigan Rogel Cancer Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine whether a reduced intensity conditioning regimen for stem cell transplant with donor cells will allow the donor cells to be effective without causing health problems.
Detailed Description
In this research study patients will receive dosages of chemotherapy that are lower than the usual dosages. The study will determine whether a shorter duration of immunosuppression will permit the donor cells to be effective against the cancer without causing more severe GVHD (Graft Versus Host Disease). Also to be determined is whether the patient's cancer can be prevented from relapsing after blood stem cell transplant by using prophylactic treatment, giving a donor leukocyte infusion BEFORE a relapse happens. In this research study samples of blood and bone marrow will be analyzed. These samples will be examined to study the cellular production of inflammatory cytokine levels in attempt to be able to predict which patients will have complications like GVHD or relapse.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma, Lymphocytic Leukemia, Chronic, Lymphoma, Low-Grade

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
54 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Immunosuppression Taper
Arm Type
Experimental
Arm Description
Reduced intensity conditioning consisting of Busulfan and Fludarabine(fludarabine 150 mg/m2 IV, busulfan 6 mg/kg IV, total lymphoid irradiation 2 Gy), followed by a rapid immunosuppressive taper of Tacrolimus (0.06 mg/kg q12h, PO, Days -7 to +28), Methotrexate (5 mg/m2, IV, Days +1, +3, +6, +11) and Mycophenolate Mofetil (10 mg/kg every 8 hours, PO, Days -6 to +7).
Intervention Type
Procedure
Intervention Name(s)
Reduced intensity conditioning
Intervention Description
Busulfan and Fludarabine regimen
Intervention Type
Procedure
Intervention Name(s)
Rapid immunosuppressive taper
Intervention Description
Taper of Tacrolimus, Methotrexate and Mycophenolate Mofetil
Intervention Type
Procedure
Intervention Name(s)
Prophylactic donor leukocyte infusions
Intervention Description
If the patient has GVHD overall grade 0-1 or skin grade 1 on day +100, then 5 x 107 CD3+ cells/kg recipient weight are given.
Primary Outcome Measure Information:
Title
Percentage of Participants With Acute Graft Versus Host Disease (GVHD) Grades 2-4
Description
The primary objective of this study was to establish the rate of acute GVHD following prophylactic cellular immunotherapy after allogeneic hematopoietic stem cell therapy using low intensity conditioning for high-risk hematological malignancies. Glucksberg staging was used for organ grading of GVHD. Clinical GVHD was assessed as follows: Grade 0: No stage 1-4 of any organ Grade 1: Stage 1-2 rash and no liver or gut involvement Grade 2: Stage 3 rash, or Stage 1 liver involvement, or Stage 1 GI Grade 3: Stage 0-3 skin with Stage 2-3 liver, or Stage 2-4 GI Grade 4: Stage 4 skin rash, or Stage 4 liver involvement
Time Frame
100 days
Title
Percentage of Participants With Progression Free Survival
Description
The second primary objective was to determine the percentage of participants with progression free survival following prophylactic cellular immunotherapy after allogeneic hematopoietic stem cell therapy using low intensity conditioning for high-risk hematological malignancies. We define disease progression as disease recurrence within 180 days of transplant.
Time Frame
two years
Secondary Outcome Measure Information:
Title
Percentage of Patients Alive at 2 Years
Description
To estimate the overall survival of patients progression following prophylactic cellular immunotherapy after allogeneic hematopoietic stem cell therapy using low intensity conditioning for high-risk hematological malignancies.
Time Frame
2 Years

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Patient Inclusion Criteria: To be eligible a patient MUST meet at least one of the next 4 criteria Any patient aged 55 years or older with a hematological malignancy for which allogeneic transplant is considered an appropriate treatment, AND/OR Any patient, regardless of age, with a hematologic malignancy for which allogeneic transplant is considered an appropriate treatment and the patient is not eligible for a conventional myeloablative transplant because of organ dysfunction AND/OR Any patient, regardless of age, who has relapsed following prior autologous or allogeneic transplant for a hematologic malignancy AND/OR Any patient, regardless of age, with one of the following hematological malignancies: Multiple myeloma refractory to or failure following conventional chemotherapy such as VAD (Vincristine, Adriamycin and Dexamethasone), pulse decadron, or alkylating agents, or chromosomal abnormality associated with poor prognosis by cytogenetics or FISH probe. Chronic lymphocytic leukemia patients, Rai stage 3 or 4 and relapsed following/refractory to alkylating agents or nucleoside analog therapy Low grade lymphoma (small lymphocytic, follicular small cleaved cell, or follicular mixed small cleaved and large cell) that is either relapsed or refractory provided the disease is NOT rapidly progressive, NOT bulky, and no mass exceeds 5 cm in greatest dimension. To be eligible a patient MUST meet all of the following criteria In addition to the above criteria ALL patients must meet the following minimum organ function: Cardiac: Ejection fraction at least 30%. Renal: Adequate renal function as defined by creatinine < 2.0mg OR creatinine clearance >40 mg/min by 24-hour urine collection or GFR (Glomerular Filtration Rate. (Gender and age-adjusted creatinine clearance >40ml/min by Gault-Cockroft 55 is acceptable for adults: (140 - age) x weight/72 x Scr [x 0.85 if female]). Pulmonary: FEV1 and FVC >60%. Hepatic: Total bilirubin <2.0 and AST (Aspartate Aminotransferase)/ALT (Alanine Transaminase) < 3X institutional normal for age. Performance (adults): Karnofsky score must be at least 60; for pts. under 16, Lansky score must be at least 60. Availability of a 5/6 or 6/6 HLA A, B, and DR identical relative who is willing and able to donate allogeneic stem cells. Serological, low resolution or mid resolution molecular typing will determine the degree of match for HLA (Human Leukocyte Antigen) class I regardless of high resolution DNA typing results. High resolution typing will be used to determine the degree of match for HLA-DR. No untreated or uncontrolled invasive infections. Patients still under therapy for presumed or proven infection are eligible provided there is clear evidence (radiologic and/or culture) that the infection is well controlled. Patients under treatment for infection will be enrolled only after clearance from the Principal Investigator. Not pregnant Patient Exclusion Criteria: acute leukemia HIV positive patients not eligible Any physical or psychological condition that, in the opinion of the investigator, would pose unacceptable risk to the patient Pregnant Donor Inclusion Criteria: 5/6 or 6/6 HLA match for HLA-A, B, and DR Age 3-70 years, good general health No contraindication to G-CSF (Granulocyte Colony-Stimulating Factor)stimulation No contraindication to leukapheresis of peripheral blood stem cells Good general health Donor Exclusion Criteria: HIV positive or history of HIV risk factors Presence of other diseases transmissible by blood that pose unacceptable risk to the study subject. Pregnant Medical or psychological conditions that would make the donor unlikely to tolerate G-CSF - injections or leukapheresis
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John E. Levine, MD, MS
Organizational Affiliation
The Univeristy of Michigan
Official's Role
Principal Investigator
Facility Information:
Facility Name
The University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States

12. IPD Sharing Statement

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Study of Low-Intensity Conditioning for Allogeneic Stem Cell Transplant

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