Reduced Intensity Conditioning and Haploidentical Related Bone Marrow for Patients With Hematologic Diseases
Study Details
Study Description
Brief Summary
This is a treatment guideline for HLA-Haploidentical hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) regimen. This regimen, consisting of fludarabine, cyclophosphamide and low dose total body irradiation (TBI), is designed for the treatment of patients with advanced and/or high risk diseases.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Haploidentical stem cell transplant This is a treatment guideline for HLA-Haploidentical hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) regimen. This regimen consists of fludarabine, cyclophosphamide and low dose total body irradiation (TBI). |
Drug: Fludarabine
Fludarabine 30 mg/m2 IV over 30-60 minutes on days -6 through -2 before transplant.
Other Names:
Drug: Cyclophosphamide
Cyclophosphamide 14.5 mg/kg IV over 1-2 hours on days -6 and -5 before transplant and Cyclophosphamide 50 mg/kg IV on days 3 and 4 post-transplant.
Radiation: Total Body Irradiation
TBI 200cGy on day -1 before transplant.
Other Names:
Biological: Haploidentical stem cell transplant
Non-T-cell depleted bone marrow infusion
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 2 Year Survival [2 years]
Percentage of patients that survive 2 years post-transplant
Secondary Outcome Measures
- Number of Patients With Hematopoietic Engraftment [42 days]
Engraftment is defined as absolute neutrophil count (ANC) ≥ 5 X 10^8/L for 3 consecutive measurements.
- Number of Patients With Chimerism [100 days]
Number of patients with chimerism at day 100, 6 months and 1 year
- Number of Patients Experiencing Acute Graft-versus-host Disease by 100 Days [100 days]
- Number of Patients Experiencing Chronic Graft-versus-host Disease by 1 Year [1 year]
- Number of Patients Experiencing Transplant Related Mortality (TRM) [6 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Must be <75 years old with no 7/8 or 8/8 HLA-matched sibling donor
-
One or more potential related mismatched donors (e.g. biologic parent (s) or siblings (full or half) or children). Low resolution using DNA based typing at HLA-A, -B and -DRB1 for potential haploidentical donors is required.
-
All diseases listed below are advanced hematologic malignancies not curable by conventional chemotherapy. Responses to conventional treatment range from zero to 30% but are typically short lived.
-
Acute Lymphoblastic Leukemia (ALL) in first complete remission (CR1) that is NOT considered favorable-risk.
-
Acute Myelogenous Leukemia (AML) in first complete remission (CR1) that is NOT considered as favorable-risk.
-
Acute Leukemias in 2nd or subsequent CR
-
Biphenotypic/Undifferentiated/Prolymphocytic Leukemias in first or subsequent CR, adult T-cell leukemia/lymphoma in first or subsequent CR
-
Burkitt's lymphoma in CR2 or subsequent CR
-
Natural killer cell malignancies after response to initial therapy
-
Chronic myelogenous leukemia: all types except refractory blast crisis.
-
Large-cell lymphoma, Hodgkin lymphoma and multiple myeloma with chemotherapy sensitive disease that has failed or patients who are ineligible for an autologous transplant.
-
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, follicular lymphoma, which have progressed within 12 months of achieving a partial or complete remission.
-
Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy if chemotherapy sensitive.
-
Refractory leukemia or MDS These patients may be taken to transplant in aplasia after induction or re-induction chemotherapy or radiolabeled antibody.
-
Bone marrow failure syndromes, except for Fanconi Anemia
-
Myeloproliferative syndromes
-
Adequate organ function is defined as:
-
Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction > 35%. For children that are not able to cooperate with multigated acquisition scan (MUGA) and echocardiography, such should be clearly stated in the physician's note
-
Pulmonary: Diffusing capacity of lung for carbon monoxide (DLCO) > 30% predicted, and absence of O2 requirements. For children that are not able to cooperate with pulmonary function tests (PFTs), a pulse oximetry with exercise should be attempted. If nether test can be obtained it should be clearly stated in the physician's note.
-
Liver: Transaminases < 5 x upper limit of normal and bilirubin < 3 x upper limit of normal
-
Renal: serum creatinine < 2.0 mg/dl (adults) or glomerular filtration rate (GFR)
40 mL/min/1.73m2 (peds). Patients with a creatinine > 1.2 mg/dl or a history of renal dysfunction must have glomerular filtration rate (GFR) > 40 mL/min/1.73m2.
-
Adequate performance status is defined as Karnofsky score ≥ 60% (> 16 years of age) or Lansky score ≥ 50 (pediatrics)
-
If recent mold infection e.g. Aspergillus - must have minimum of 30 days of appropriate treatment before bone marrow transplant (BMT) and infection controlled and be cleared by Infectious Disease.
-
Second BMT: Must be > 3 months after prior myeloablative transplant.
-
Patients must be ineligible for autologous transplantation due to prior autologous transplant, an inadequate autologous stem cell harvest, inability to withstand a myeloablative preparative regimen, or clinically aggressive/high risk disease.
-
Patients are eligible for transplantation if there is no evidence of progressive disease by imaging modalities or biopsy. Persistent PET activity, though possibly related to lymphoma, is not an exclusion criterion in the absence of CT changes indicating progression.
-
Patients with stable disease are eligible for transplantation if the largest residual nodal mass is < 5 cm (approximately). For patients who have responded to preceding therapy, the largest residual mass must represent a 50% reduction and be < 7.5 cm (approximately).
-
Voluntary written consent (adult or parental/guardian)
Exclusion Criteria:
-
Available and clinically suitable 5-6/6 HLA-A, B, DRB1 matched sibling donor
-
Pregnant or breastfeeding
-
Evidence of HIV infection or known HIV positive serology
-
Current active serious infection
-
Unless in post-chemotherapy and radioimmunoconjugated antibody induced aplasia, when he/she would be eligible, patients with acute leukemia in morphologic relapse/ persistent disease defined as > 5% blasts in normocellular bone marrow OR any % blasts if blasts have unique morphologic markers (e.g. Auer rods) or associated cytogenetic markers that allows morphologic relapse to be distinguished are not eligible.
-
Chronic myeloid leukemia (CML) in refractory blast crisis
-
Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressive on salvage therapy. Stable disease is acceptable to move forward provided it is non-bulky.
-
active central nervous system malignancy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Minnesota Masonic Cancer Center | Minneapolis | Minnesota | United States | 55455 |
Sponsors and Collaborators
- Masonic Cancer Center, University of Minnesota
Investigators
- Principal Investigator: Claudio Brunstein, MD, University of Minnesota
Study Documents (Full-Text)
More Information
Publications
None provided.- 2013OC116
- MT2013-33C
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Haploidentical Stem Cell Transplant |
|---|---|
| Arm/Group Description | This is a treatment guideline for HLA-Haploidentical hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) regimen. This regimen consists of fludarabine, cyclophosphamide and low dose total body irradiation (TBI). Fludarabine: Fludarabine 30 mg/m2 IV over 30-60 minutes on days -6 through -2 before transplant. Cyclophosphamide: Cyclophosphamide 14.5 mg/kg IV over 1-2 hours on days -6 and -5 before transplant and Cyclophosphamide 50 mg/kg IV on days 3 and 4 post-transplant. Total Body Irradiation: TBI 200cGy (centigray) on day -1 before transplant. Haploidentical stem cell transplant: Non-T-cell depleted bone marrow infusion |
| Period Title: Overall Study | |
| STARTED | 2 |
| COMPLETED | 2 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Haploidentical Stem Cell Transplant |
|---|---|
| Arm/Group Description | This is a treatment guideline for HLA-Haploidentical hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) regimen. This regimen consists of fludarabine, cyclophosphamide and low dose total body irradiation (TBI). Fludarabine: Fludarabine 30 mg/m2 IV over 30-60 minutes on days -6 through -2 before transplant. Cyclophosphamide: Cyclophosphamide 14.5 mg/kg IV over 1-2 hours on days -6 and -5 before transplant and Cyclophosphamide 50 mg/kg IV on days 3 and 4 post-transplant. Total Body Irradiation: TBI 200cGy on day -1 before transplant. Haploidentical stem cell transplant: Non-T-cell depleted bone marrow infusion |
| Overall Participants | 2 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
1
50%
|
| >=65 years |
1
50%
|
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
67
(7)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
2
100%
|
| Male |
0
0%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
0
0%
|
| Not Hispanic or Latino |
2
100%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
0
0%
|
| White |
2
100%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
2
100%
|
Outcome Measures
| Title | 2 Year Survival |
|---|---|
| Description | Percentage of patients that survive 2 years post-transplant |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Haploidentical Stem Cell Transplant |
|---|---|
| Arm/Group Description | This is a treatment guideline for HLA-Haploidentical hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) regimen. This regimen consists of fludarabine, cyclophosphamide and low dose total body irradiation (TBI). Fludarabine: Fludarabine 30 mg/m2 IV over 30-60 minutes on days -6 through -2 before transplant. Cyclophosphamide: Cyclophosphamide 14.5 mg/kg IV over 1-2 hours on days -6 and -5 before transplant and Cyclophosphamide 50 mg/kg IV on days 3 and 4 post-transplant. Total Body Irradiation: TBI 200cGy on day -1 before transplant. Haploidentical stem cell transplant: Non-T-cell depleted bone marrow infusion |
| Measure Participants | 2 |
| Count of Participants [Participants] |
0
0%
|
| Title | Number of Patients With Hematopoietic Engraftment |
|---|---|
| Description | Engraftment is defined as absolute neutrophil count (ANC) ≥ 5 X 10^8/L for 3 consecutive measurements. |
| Time Frame | 42 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Haploidentical Stem Cell Transplant |
|---|---|
| Arm/Group Description | This is a treatment guideline for HLA-Haploidentical hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) regimen. This regimen consists of fludarabine, cyclophosphamide and low dose total body irradiation (TBI). Fludarabine: Fludarabine 30 mg/m2 IV over 30-60 minutes on days -6 through -2 before transplant. Cyclophosphamide: Cyclophosphamide 14.5 mg/kg IV over 1-2 hours on days -6 and -5 before transplant and Cyclophosphamide 50 mg/kg IV on days 3 and 4 post-transplant. Total Body Irradiation: TBI 200cGy on day -1 before transplant. Haploidentical stem cell transplant: Non-T-cell depleted bone marrow infusion |
| Measure Participants | 2 |
| Count of Participants [Participants] |
2
100%
|
| Title | Number of Patients With Chimerism |
|---|---|
| Description | Number of patients with chimerism at day 100, 6 months and 1 year |
| Time Frame | 100 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Chimerism at 6 months and 1 year not evaluated |
| Arm/Group Title | Haploidentical Stem Cell Transplant |
|---|---|
| Arm/Group Description | This is a treatment guideline for HLA-Haploidentical hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) regimen. This regimen consists of fludarabine, cyclophosphamide and low dose total body irradiation (TBI). Fludarabine: Fludarabine 30 mg/m2 IV over 30-60 minutes on days -6 through -2 before transplant. Cyclophosphamide: Cyclophosphamide 14.5 mg/kg IV over 1-2 hours on days -6 and -5 before transplant and Cyclophosphamide 50 mg/kg IV on days 3 and 4 post-transplant. Total Body Irradiation: TBI 200cGy on day -1 before transplant. Haploidentical stem cell transplant: Non-T-cell depleted bone marrow infusion |
| Measure Participants | 2 |
| Chimerism at day 100 |
2
100%
|
| Chimerism at 6 months |
NA
NaN
|
| Chimerism at 1 year |
NA
NaN
|
| Title | Number of Patients Experiencing Acute Graft-versus-host Disease by 100 Days |
|---|---|
| Description | |
| Time Frame | 100 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Haploidentical Stem Cell Transplant |
|---|---|
| Arm/Group Description | This is a treatment guideline for HLA-Haploidentical hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) regimen. This regimen consists of fludarabine, cyclophosphamide and low dose total body irradiation (TBI). Fludarabine: Fludarabine 30 mg/m2 IV over 30-60 minutes on days -6 through -2 before transplant. Cyclophosphamide: Cyclophosphamide 14.5 mg/kg IV over 1-2 hours on days -6 and -5 before transplant and Cyclophosphamide 50 mg/kg IV on days 3 and 4 post-transplant. Total Body Irradiation: TBI 200cGy on day -1 before transplant. Haploidentical stem cell transplant: Non-T-cell depleted bone marrow infusion |
| Measure Participants | 2 |
| Count of Participants [Participants] |
1
50%
|
| Title | Number of Patients Experiencing Chronic Graft-versus-host Disease by 1 Year |
|---|---|
| Description | |
| Time Frame | 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected for this Outcome Measure as both participants died by the 6 month time point |
| Arm/Group Title | Haploidentical Stem Cell Transplant |
|---|---|
| Arm/Group Description | This is a treatment guideline for HLA-Haploidentical hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) regimen. This regimen consists of fludarabine, cyclophosphamide and low dose total body irradiation (TBI). Fludarabine: Fludarabine 30 mg/m2 IV over 30-60 minutes on days -6 through -2 before transplant. Cyclophosphamide: Cyclophosphamide 14.5 mg/kg IV over 1-2 hours on days -6 and -5 before transplant and Cyclophosphamide 50 mg/kg IV on days 3 and 4 post-transplant. Total Body Irradiation: TBI 200cGy on day -1 before transplant. Haploidentical stem cell transplant: Non-T-cell depleted bone marrow infusion |
| Measure Participants | 0 |
| Title | Number of Patients Experiencing Transplant Related Mortality (TRM) |
|---|---|
| Description | |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Haploidentical Stem Cell Transplant |
|---|---|
| Arm/Group Description | This is a treatment guideline for HLA-Haploidentical hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) regimen. This regimen consists of fludarabine, cyclophosphamide and low dose total body irradiation (TBI). Fludarabine: Fludarabine 30 mg/m2 IV over 30-60 minutes on days -6 through -2 before transplant. Cyclophosphamide: Cyclophosphamide 14.5 mg/kg IV over 1-2 hours on days -6 and -5 before transplant and Cyclophosphamide 50 mg/kg IV on days 3 and 4 post-transplant. Total Body Irradiation: TBI 200cGy on day -1 before transplant. Haploidentical stem cell transplant: Non-T-cell depleted bone marrow infusion |
| Measure Participants | 2 |
| Count of Participants [Participants] |
1
50%
|
Adverse Events
| Time Frame | 2 years post-transplant | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Haploidentical Stem Cell Transplant | |
| Arm/Group Description | This is a treatment guideline for HLA-Haploidentical hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) regimen. This regimen consists of fludarabine, cyclophosphamide and low dose total body irradiation (TBI). Fludarabine: Fludarabine 30 mg/m2 IV over 30-60 minutes on days -6 through -2 before transplant. Cyclophosphamide: Cyclophosphamide 14.5 mg/kg IV over 1-2 hours on days -6 and -5 before transplant and Cyclophosphamide 50 mg/kg IV on days 3 and 4 post-transplant. Total Body Irradiation: TBI 200cGy on day -1 before transplant. Haploidentical stem cell transplant: Non-T-cell depleted bone marrow infusion | |
All Cause Mortality |
||
| Haploidentical Stem Cell Transplant | ||
| Affected / at Risk (%) | # Events | |
| Total | 2/2 (100%) | |
Serious Adverse Events |
||
| Haploidentical Stem Cell Transplant | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/2 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Haploidentical Stem Cell Transplant | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/2 (0%) | |
Limitations/Caveats
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. Claudio Brunstein |
|---|---|
| Organization | University of Minnesota Cancer Center |
| Phone | 612-625-8942 |
| bruns072@umn.edu |
- 2013OC116
- MT2013-33C