Mismatched Transplantation Using High-dose Post-transplant Cyclophosphamide

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01010217
• Collaborator: (none)
• Enrollment: 176
• Location: 1
• Arms: 3
• Actual Duration (Months): 95
• Patients Per Site Per Month: 1.9

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to learn about the safety of giving a stem cell transplant from a tissue-mismatched donor, followed by cyclophosphamide, to patients with certain types of blood disorders or blood cancers. Melphalan, thiotepa, and fludarabine will also be given before the transplant.

Researchers will study the health status of these patients at 3 months after the transplant.

Condition or Disease	Intervention/Treatment	Phase
Blood Stem Cell Transplant Failure; Leukemia; Hematologic Malignancies	Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Melphalan; Drug: Mesna; Drug: Rituximab; Procedure: Stem Cell Transplantation; Drug: Thiotepa; Drug: Tacrolimus; Drug: Mycofenolate mofetil; Drug: G-CSF	Phase 2

Detailed Description

The Study Treatment:

Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may slow or stop their growth and spread throughout the body. This may cause the cancer cells to die.

In this study, researchers want to learn if cyclophosphamide can help to prevent graft-versus-host disease (GVHD -- when transplanted immune tissue, such as white blood cells, attacks the tissues of the recipient's body).

Melphalan, thiotepa, and fludarabine are commonly used in combination with a stem cell transplant.

Study Treatment Administration:

If you are found to be eligible to take part in this study, you will receive chemotherapy for 6 days:

• You will receive melphalan by vein over 30 minutes on Day -8 (8 days before the transplant).

• You will receive thiotepa by vein over 4 hours on Day -7.

• You will receive fludarabine by vein over 1 hour on Days -6, -5, -4, and -3.

If thiotepa is not available, you will receive melphalan by vein over 30 minutes on Day -6 and fludarabine by vein over 1 hour on Days -5, -4, -3, and -2. You will receive total body irradiation (TBI) on Day -1.

On Day 0, you will receive the donor's stem cells by vein. This may last anywhere from 15 minutes to several hours.

On Days 3 and 4, you will receive cyclophosphamide by vein over 3 hours. You will also receive mesna by vein over 30 minutes every 4 hours for a total of 10 mesna doses on Days 3 and 4. Mesna is given to lower the risk of side effects to the bladder.

Starting on Day 5, you will receive tacrolimus and mycophenolate mofetil (MMF) to help lower the risk of GVHD. Tacrolimus will be given by vein as a continuous infusion for about 2 weeks. After the 2 weeks of taking tacrolimus by vein, you will take tacrolimus by mouth as a pill for at least 3 months. MMF will be given by mouth, 3 times a day, usually until Day 35.

Starting on Day 7, you will receive filgrastim (G-CSF) once a day as an injection under the skin, until your blood cell counts reach a high enough level.

Depending on the type of disease that you have, your doctor may decide to give you rituximab by vein over several hours on Days -13, -6, 1, and 8. Rituximab is given to help the body get rid of abnormal white blood cells.

Length of Study Participation:

You will be in the hospital for about 4 weeks after the transplant. You will be taken off study if the disease gets worse. The study drugs will be stopped if intolerable side effects occur.

Follow-Up Visits:

You will be asked to stay close enough to Houston to be able to come back for any visits for at least 100 days after the transplant.

At 1, 3, 6, and 12 months after the transplant, the following tests and procedures will be performed:

• You will have a physical exam.

• Blood (about 4 tablespoons) will be drawn for routine tests.

• You will have a bone marrow biopsy/aspirate to check the status of the disease. If you have lymphoma or aplastic anemia, you may have a bone marrow biopsy/aspirate at 3, 6, and 12 months, if your doctor thinks it is needed.

• Blood (about 4 tablespoons) will be drawn to measure tumor cells and to predict graft failure and/or relapse.

• You may have urine collected and/or scans performed such as x-rays, CT scans, and/or a positron emission tomography (PET) scan. These scans and urine tests would only be done if the study doctor thinks they are needed to check the status of the disease.

• Blood (about 4 tablespoons) will be drawn to check your immune system.

If you have AML, at 2 months after the transplant, blood (about 4 tablespoons) will be drawn to check your immune system.

If you have MM, you will have a bone survey once a year.

If the study doctor thinks it is needed based on side effects you may be having, additional follow-up tests will be performed.

You may be contacted by phone 1-2 times a year to ask about the status of the disease. These calls will take about 10 minutes to complete.

This is an investigational study. All of the drugs used in this study are commercially available and FDA approved. However, it is investigational to give high-dose cyclophosphamide for preventing GVHD that may occur after a stem cell transplant from a tissue-mismatched donor.

Up to 337 patients will take part in this study. All will be enrolled at MD Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 176 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Three-arm Clinical Trial for Patients With Hematologic Malignancies and Mismatched Donors - Haploidentical, 1 Antigen Mismatch Related or Unrelated, and Matched Unrelated Donor (MUD)- Using a T-cell Replete Allograft and High-dose Post-transplant Cyclophosphamide
• Actual Study Start Date: Nov 5, 2009
• Actual Primary Completion Date: Oct 5, 2017
• Actual Study Completion Date: Oct 5, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Haploidentical related Arm 1 - Stem Cell Transplantation (SCT), Melphalan 140 mg/m^2 , Thiotepa 5 mg/kg, Fludarabine 40 mg/m^2 + high-dose post-transplant cyclophosphamide 50 mg/kg/day	Drug: Cyclophosphamide; 50 mg/kg/day intravenous (IV) over 3 hours on Days 3 and 4.; Other Names: Cytoxan Neosar ; Drug: Fludarabine; 40 mg/m^2 IV over 1 hour on Days -6, -5, -4, and -3.; Other Names: Fludara Fludarabine Phosphate ; Drug: Melphalan; 140 mg/m^2 IV (or 100 mg/m^2 with reduced intensity Regimen 2) over 30 minutes on Day -8.; Other Names: Alkeran ; Drug: Mesna; 10 mg/kg IV every 4 hours for a total of 10 doses starting just prior to first dose of Cyclophosphamide on Days 3 and 4.; Other Names: Mesnex ; Drug: Rituximab; CD20+ lymphoid malignancies: 375 mg/m2 on Day -13 followed by 1000 mg/m2 on Day -6, +1, and +8.; Other Names: Rituxan ; Procedure: Stem Cell Transplantation; Infusion of donor's stem cells by vein on Day 0, may last anywhere from 15 minutes to several hours.; Other Names: SCT Blood Marrow Transplantation Allogeneic stem cell transplantation ASCT ; Drug: Thiotepa; 5 mg/kg Regimen 1 (or 5 mg/kg with reduced intensity Regimen 2) IV over 4 hours on Day -7.; Drug: Tacrolimus; 0.015 mg/kg by vein or orally daily starting on Day +5 for 3 months; Other Names: Prograf ; Drug: Mycofenolate mofetil; 15 mg/kg/dose orally three times a day starting on Day +5 to Day +100 or otherwise indicated; Other Names: MMF CellCept ; Drug: G-CSF; 5 mcg/kg/day subcutaneously starting Day 7 once a day daily until neutrophil recovery > 1000/mcl.; Other Names: Filgrastim Neupogen
Experimental: 1 Antigen Mismatch Related or Unrelated Arm 2 - SCT, Melphalan, Thiotepa, Fludarabine + high-dose post-transplant cyclophosphamide.	Drug: Cyclophosphamide; 50 mg/kg/day intravenous (IV) over 3 hours on Days 3 and 4.; Other Names: Cytoxan Neosar ; Drug: Fludarabine; 40 mg/m^2 IV over 1 hour on Days -6, -5, -4, and -3.; Other Names: Fludara Fludarabine Phosphate ; Drug: Melphalan; 140 mg/m^2 IV (or 100 mg/m^2 with reduced intensity Regimen 2) over 30 minutes on Day -8.; Other Names: Alkeran ; Drug: Mesna; 10 mg/kg IV every 4 hours for a total of 10 doses starting just prior to first dose of Cyclophosphamide on Days 3 and 4.; Other Names: Mesnex ; Drug: Rituximab; CD20+ lymphoid malignancies: 375 mg/m2 on Day -13 followed by 1000 mg/m2 on Day -6, +1, and +8.; Other Names: Rituxan ; Procedure: Stem Cell Transplantation; Infusion of donor's stem cells by vein on Day 0, may last anywhere from 15 minutes to several hours.; Other Names: SCT Blood Marrow Transplantation Allogeneic stem cell transplantation ASCT ; Drug: Thiotepa; 5 mg/kg Regimen 1 (or 5 mg/kg with reduced intensity Regimen 2) IV over 4 hours on Day -7.; Drug: Tacrolimus; 0.015 mg/kg by vein or orally daily starting on Day +5 for 3 months; Other Names: Prograf ; Drug: Mycofenolate mofetil; 15 mg/kg/dose orally three times a day starting on Day +5 to Day +100 or otherwise indicated; Other Names: MMF CellCept ; Drug: G-CSF; 5 mcg/kg/day subcutaneously starting Day 7 once a day daily until neutrophil recovery > 1000/mcl.; Other Names: Filgrastim Neupogen
Experimental: Matched Unrelated Donor (MUD) Arm 3 - SCT, Melphalan, Thiotepa, Fludarabine + high-dose post-transplant cyclophosphamide	Drug: Cyclophosphamide; 50 mg/kg/day intravenous (IV) over 3 hours on Days 3 and 4.; Other Names: Cytoxan Neosar ; Drug: Fludarabine; 40 mg/m^2 IV over 1 hour on Days -6, -5, -4, and -3.; Other Names: Fludara Fludarabine Phosphate ; Drug: Melphalan; 140 mg/m^2 IV (or 100 mg/m^2 with reduced intensity Regimen 2) over 30 minutes on Day -8.; Other Names: Alkeran ; Drug: Mesna; 10 mg/kg IV every 4 hours for a total of 10 doses starting just prior to first dose of Cyclophosphamide on Days 3 and 4.; Other Names: Mesnex ; Drug: Tacrolimus; 0.015 mg/kg by vein or orally daily starting on Day +5 for 3 months; Other Names: Prograf ; Drug: Mycofenolate mofetil; 15 mg/kg/dose orally three times a day starting on Day +5 to Day +100 or otherwise indicated; Other Names: MMF CellCept ; Drug: G-CSF; 5 mcg/kg/day subcutaneously starting Day 7 once a day daily until neutrophil recovery > 1000/mcl.; Other Names: Filgrastim Neupogen

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Non-relapse Mortality (NRM) [At 100 days]

   Non-relapse mortality (NRM) is defined as death from any cause other than relapse disease. Bayesian monitoring scheme described in Thall, Simon, and Estey (1996) employed to perform interim monitoring of the data during the course of the trial separately within each group.

Secondary Outcome Measures

1. Number of Participants With Non Related Mortality (NRM) [six months]

   Non-relapse mortality (NRM) is defined as death from any cause other than relapse disease.

2. Engraftments [Day 28]

3. Grade III-IV aGVHD [100 days]

   Acute Graft vs host disease

4. cGVHD [1 year]

   Chronic graft vs host disease

5. Disease Free Survival [1 year]

   Participants who have survived without their original disease.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients < 55 years (Myeloablative regimen #1) or > 55 and </= 75 years or significant comorbidities (Reduced intensity regimen #2) old lacking a matched related volunteer donor identified in time for transplant for which a related haploidentical donor (</= 7/8 allele match at the A, B, C, DR loci), a 7/8 allele matched related or unrelated donor is identified, or a matched unrelated donor (MUD). The patients must be diagnosed with a high-risk disease defined as following:

2. Acute lymphocytic leukemia (ALL) in CR1 with high-risk features including adverse cytogenetics such as t(9;22), t(1;19), t(4;11), or MLL gene rearrangements; ALL in second or greater remission or ALL with relapsed disease, peripheral blood blasts < 1000/microliter, ALL patients must show response to most recent received chemotherapy;

3. Acute myeloid leukemia (AML) in CR1 with intermediate-risk disease or high-risk features defined as: Greater than 1 cycle of induction therapy required to achieve remission; Preceding myelodysplastic syndrome (MDS) or myeloproliferative disease; Presence of FLT3 mutations or internal tandem duplications; FAB M6 or M7 classification; Adverse cytogenetics, -5, del 5q, -7, del7q, abnormalities involving 3q, 9q, 11q, 20q, 21q, 17, +8 [> 3 abnormalities], peripheral blood blasts <1000/microliter, AML patients must show response to most recent received chemotherapy;

4. AML in second or greater remission, primary induction failure and patients with relapsed disease, peripheral blood blasts <1000/microliter; patients > 55 years and </= 75 years need to be in morphologic remission at transplant (< 5% blasts).

5. Myelodysplastic syndrome (MDS) with International Prognostic Scoring System (IPSS) intermediate-2 or higher; or therapy-related MDS

6. Aplastic anemia with Absolute neutrophil count (ANC)<1000 and transfusion dependent after they failed immunosuppression therapy

7. Chronic myeloid leukemia (CML) >/=1st chronic phase, after failed >/=2 lines of tyrosine kinase inhibitors; in accelerated or blast phase with > 30% bone marrow blasts;

8. Prior allogeneic stem cell transplant more than 6 months from the first transplant, in remission.

9. Chemotherapy-sensitive relapsed lymphoma (Complete or partial response), Hodgkin's or non-Hodgkin's lymphoma, no evidence of "bulky" disease (> 10 cm in diameter);

10. Patients with chemo-sensitive CLL with persistent or recurrent disease after fludarabine-based regimens, no evidence of "bulky" disease (> 10 cm in diameter)

11. Patients with poor prognosis multiple myeloma by cytogenetics (del13, del 17p, t(1;14) or t(14;16) or hypodiploidy, with advanced disease (stage>/=2) and /or relapsed after autologous stem cell transplant.

12. Patients with myelofibrosis (Lille >0, transfusion dependency, progression to blast phase; however, in remission from AML) or chronic myelomonocytic leukemia (CMML). These patients will be treated with the reduced-intensity conditioning regimen #2 and will be subject to the same stopping rule as the group >/= 55 years or with comorbidities.

13. Zubrod performance status 0-1 or Lansky PS greater or equal to 70%.

14. Patients above >/=65 years old should have an age-adjusted co-morbidity index of </=

16. Available donor able to undergo a bone marrow harvest. For matched unrelated donor transplants only: Peripheral blood stem cells may be collected if donor is unavailable for bone marrow harvest or if adequate bone marrow cannot be collected.

17. Bilirubin </= 1.5 mg/dl (unless Gilbert's syndrome), ALT or AST </= 200 IU/ml.

18. Serum creatinine clearance >/=50 ml/min (calculated with Cockcroft-Gault formula); Creatinine for children </=1.5 mg/dl or </=2 times upper limit of normal for age (whichever is less);

19. Diffusing capacity for carbon monoxide (DLCO) >/= 45% predicted corrected for hemoglobin. For pediatric patients, if unable to perform pulmonary function, >/= 92% oxygen saturation with pulse oximetry.

20. Left ventricular ejection fraction (LVEF) >/= 40%.

21. Patient or patient's legal representative, parent(s) or guardian should provide written informed consent. Assent of a minor if participant's age is at least seven and less than eighteen years.

Exclusion Criteria:

1. HIV positive; active hepatitis B or C

2. Patients with active infections. The PI is the final arbiter of the eligibility.

3. Liver cirrhosis with greater than grade 1 stage 1 inflammation/fibrosis

4. Uncontrolled central nervous system (CNS) involvement by tumor cells

5. Patients with AML must have less than 30% bone marrow blasts and no peripheral blood blasts.

6. History of another primary malignancy that has not been in remission for at least 3 years. (The following are exempt from the 3-year limit: non-invasive nonmelanoma skin cancer, fully excised melanoma in situ [Stage 0], curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on PAP smear.)

7. Positive Beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.

8. Inability to comply with medical therapy or follow-up.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center

Investigators

• Study Chair: Stefan Ciurea, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 26, 2015

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT01010217
• Other Study ID Numbers: 2009-0266; NCI-2011-03144
• First Posted: Nov 9, 2009
• Last Update Posted: Mar 25, 2020
• Last Verified: Mar 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by M.D. Anderson Cancer Center: Hematologic Neoplasms; Blood Disorders; Blood Cancer; Transplantation, Blood And Marrow; Acute myelogenous leukemia; Myelodysplastic syndrome; Acute lymphocytic leukemia; Aplastic anemia; Chronic myelogenous leukemia; Chronic lymphocytic leukemia; Myeloproliferative disease; Hodgkin's disease; Non-Hodgkin's lymphoma; Multiple myeloma; Cyclophosphamide; Fludarabine; Melphalan; Mesna; Rituximab; Tacrolimus; Prograf; Mycofenolate mofetil; MMF; CellCept; G-CSF; Filgrastim; Neupogen
• Additional relevant MeSH terms: Leukemia; Neoplasms; Hematologic Neoplasms; Vidarabine; Mycophenolic Acid; Cyclophosphamide; Melphalan; Thiotepa; Rituximab; Fludarabine; Fludarabine phosphate; Tacrolimus

Study Results

Participant Flow

Recruitment Details	Patients were enrolled during the period from January 2010 through August 2014 and were assigned to the HAPLO arm or the 9/10 MUD arm based on donor availability and physician preference. The 3 arms received identical melphalan-based conditioning chemotherapy and GVHD prophylaxis
Pre-assignment Detail	Additional arm elderly patients did not accrue any participants so therefore was excluded from summary.

Arm/Group Title	Haplo Arm	1AgMM Related/Unrelated Donors	MUD Donor	Second Transplant	Myelofibrosis
Arm/Group Description	Patients that received a stem cell transplant from a haploidentical donor.	Patients that received a transplant from a 1 antigen mismatched related or unrelated donor	Patients that received a transplant from a matched unrelated donor	Patients receiving a second transplant	Patients with the diagnosis of Myelofibrosis
Period Title: Overall Study
STARTED	89	56	22	6	3
COMPLETED	84	51	21	0	0
NOT COMPLETED	5	5	1	6	3

Baseline Characteristics

Arm/Group Title	Haplo Arm	1AgMM Related/Unrelated Donors	MUD Donor	Second Transplant	Myelofibrosis	Total
Arm/Group Description	Patients that received a transplant from a haploindentical donor	Patients that received a transplant from a 1 antigen mismatched related or unrelated donor	Patients that received a transplant from a matched unrelated donor	Patients receiving a second transplant	Patients with the diagnosis of Myelofibrosis	Total of all reporting groups
Overall Participants	84	51	21	6	3	165
Age (Count of Participants)
<=18 years	2 2.4%	1 2%	0 0%	0 0%	0 0%	3 1.8%
Between 18 and 65 years	79 94%	48 94.1%	11 52.4%	6 100%	3 100%	147 89.1%
>=65 years	3 3.6%	2 3.9%	10 47.6%	0 0%	0 0%	15 9.1%
Sex: Female, Male (Count of Participants)
Female	42 50%	25 49%	6 28.6%	1 16.7%	1 33.3%	75 45.5%
Male	42 50%	26 51%	15 71.4%	5 83.3%	2 66.7%	90 54.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	10 11.9%	1 2%	0 0%	1 16.7%	0 0%	12 7.3%
Not Hispanic or Latino	69 82.1%	46 90.2%	20 95.2%	3 50%	3 100%	141 85.5%
Unknown or Not Reported	5 6%	4 7.8%	1 4.8%	2 33.3%	0 0%	12 7.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	7 8.3%	4 7.8%	0 0%	0 0%	0 0%	11 6.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	22 26.2%	7 13.7%	0 0%	0 0%	2 66.7%	31 18.8%
White	50 59.5%	36 70.6%	20 95.2%	4 66.7%	1 33.3%	111 67.3%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	5 6%	4 7.8%	1 4.8%	2 33.3%	0 0%	12 7.3%
Patients with hematologic malignancies without a matched donor (Count of Participants)
Count of Participants [Participants]	84 100%	51 100%	21 100%	6 100%	3 100%	165 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Non-relapse Mortality (NRM)
Description	Non-relapse mortality (NRM) is defined as death from any cause other than relapse disease. Bayesian monitoring scheme described in Thall, Simon, and Estey (1996) employed to perform interim monitoring of the data during the course of the trial separately within each group.
Time Frame	At 100 days

Outcome Measure Data

Analysis Population Description

Second Transplant and Myelofibrosis was not evaluated due to low accrual.

Arm/Group Title	Haplo Arm	1AgMM Related/Unrelated Donors	MUD Donor	Second Transplant	Myelofibrosis
Arm/Group Description	Patients that received a transplant from a haploidentical donor	Patients that received a transplant from a 1 antigen mismatched related or unrelated donor	Patients that received a transplant from a matched unrelated donor	Patients receiving a second transplant	Patients with the diagnosis of Myelofibrosis
Measure Participants	84	51	21	0	0
Count of Participants [Participants]	8 9.5%	7 13.7%	2 9.5%	0 0%	0 0%

2. Secondary Outcome

Title	Number of Participants With Non Related Mortality (NRM)
Description	Non-relapse mortality (NRM) is defined as death from any cause other than relapse disease.
Time Frame	six months

Outcome Measure Data

Analysis Population Description

Second Transplant and Myelofibrosis was not evaluated due to low accrual.

Arm/Group Title	Haplo Arm	1AgMM Related/Unrelated Donors	MUD Donor	Second Transplant	Myelofibrosis
Arm/Group Description	Patients that received a transplant from a haploidentical donor	Patients that received a transplant from a 1 antigen mismatched related or unrelated donor	Patients that received a transplant from a matched unrelated donor	Patients receiving a second transplant	Patients with the diagnosis of Myelofibrosis
Measure Participants	84	51	21	0	0
Count of Participants [Participants]	17 20.2%	15 29.4%	4 19%	0 0%	0 0%

3. Secondary Outcome

Title	Engraftments
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

Second Transplant and Myelofibrosis was not evaluated due to low accrual.

Arm/Group Title	Haplo Arm	1AgMM Related/Unrelated Donors	MUD Donor	Second Transplant	Myelofibrosis
Arm/Group Description	Patients that received a transplant from a haploidentical donor	Patients that received a transplant from a 1 antigen mismatched related or unrelated donor	Patients that received a transplant from a matched unrelated donor	Patients receiving a second transplant	Patients with the diagnosis of Myelofibrosis
Measure Participants	84	51	21	0	0
Count of Participants [Participants]	80 95.2%	50 98%	21 100%	0 0%	0 0%

4. Secondary Outcome

Title	Grade III-IV aGVHD
Description	Acute Graft vs host disease
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

Second Transplant and Myelofibrosis was not evaluated due to low accrual

Arm/Group Title	Haplo Arm	1AgMM Related/Unrelated Donors	MUD Donor	Second Transplant	Myelofibrosis
Arm/Group Description	Patients that received a transplant from a haploidentical donor	Patients that received a transplant from a 1 antigen mismatched related or unrelated donor	Patients that received a transplant from a matched unrelated donor	Patients receiving a second transplant	Patients with the diagnosis of Myelofibrosis
Measure Participants	84	51	21	0	0
Count of Participants [Participants]	11 13.1%	7 13.7%	1 4.8%	0 0%	0 0%

5. Secondary Outcome

Title	cGVHD
Description	Chronic graft vs host disease
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Second Transplant and Myelofibrosis was not evaluated due to low accrual.

Arm/Group Title	Haplo Arm	1AgMM Related/Unrelated Donors	MUD Donor	Second Transplant	Myelofibrosis
Arm/Group Description	Patients that received a transplant from a haploidentical donor	Patients that received a transplant from a 1 antigen mismatched related or unrelated donor	Patients that received a transplant from a matched unrelated donor	Patients receiving a second transplant	Patients with the diagnosis of Myelofibrosis
Measure Participants	84	51	21	0	0
Count of Participants [Participants]	11 13.1%	7 13.7%	0 0%	0 0%	0 0%

6. Secondary Outcome

Title	Disease Free Survival
Description	Participants who have survived without their original disease.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Second Transplant and Myelofibrosis was not evaluated due to low accrual.

Arm/Group Title	Haplo Arm	1AgMM Related/Unrelated Donors	MUD Donor	Second Transplant	Myelofibrosis
Arm/Group Description	Patients that received a transplant from a haploidentical donor	Patients that received a transplant from a 1 antigen mismatched related or unrelated donor	Patients that received a transplant from a matched unrelated donor	Patients receiving a second transplant	Patients with the diagnosis of Myelofibrosis
Measure Participants	84	51	21	0	0
Count of Participants [Participants]	50 59.5%	24 47.1%	12 57.1%	0 0%	0 0%

Adverse Events

Time Frame	From the start of the preparative regiment up to day 100.
Arm/Group Title	Haplo Arm		1AgMM Related/Unrelated Donors		MUD Donor		Second Transplant		Myelofibrosis
Arm/Group Description	Patients that received a transplant from a haploindentical donor		Patients that received a transplant from a 1 antigen mismatched related or unrelated donor		Patients that received a transplant from a matched unrelated donor		Patients receiving a second transplant		Patients with the diagnosis of Myelofibrosis
All Cause Mortality
	Haplo Arm		1AgMM Related/Unrelated Donors		MUD Donor		Second Transplant		Myelofibrosis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/84 (26.2%)		21/51 (41.2%)		9/21 (42.9%)		2/6 (33.3%)		2/3 (66.7%)
Serious Adverse Events
	Haplo Arm		1AgMM Related/Unrelated Donors		MUD Donor		Second Transplant		Myelofibrosis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/84 (9.5%)		11/51 (21.6%)		7/21 (33.3%)		2/6 (33.3%)		2/3 (66.7%)
Blood and lymphatic system disorders
Graft failure	1/84 (1.2%)		1/51 (2%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Cardiac disorders
Cardiomyopathy	3/84 (3.6%)		0/51 (0%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Gastrointestinal disorders
Chronic GI GVHD	2/84 (2.4%)		0/51 (0%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
GI GVHD	2/84 (2.4%)		4/51 (7.8%)		2/21 (9.5%)		0/6 (0%)		0/3 (0%)
Upper GI GVHD	0/84 (0%)		1/51 (2%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
General disorders
Headache	0/84 (0%)		1/51 (2%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Infections and infestations
Adenocirus viremia	1/84 (1.2%)		0/51 (0%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Bacterial infection	2/84 (2.4%)		2/51 (3.9%)		1/21 (4.8%)		2/6 (33.3%)		0/3 (0%)
Fungal infection	1/84 (1.2%)		0/51 (0%)		0/21 (0%)		0/6 (0%)		1/3 (33.3%)
Viral infection	1/84 (1.2%)		1/51 (2%)		2/21 (9.5%)		0/6 (0%)		1/3 (33.3%)
Nervous system disorders
Altered mental status	1/84 (1.2%)		0/51 (0%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Renal and urinary disorders
Acute renal failure	1/84 (1.2%)		0/51 (0%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
BK virus associated hemorrhagic cystitis	2/84 (2.4%)		0/51 (0%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Respiratory, thoracic and mediastinal disorders
ARDS	1/84 (1.2%)		2/51 (3.9%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Pneumonitis	2/84 (2.4%)		0/51 (0%)		1/21 (4.8%)		0/6 (0%)		0/3 (0%)
Fungal pneumonia	0/84 (0%)		1/51 (2%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Pulmonary edema	0/84 (0%)		0/51 (0%)		1/21 (4.8%)		0/6 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Haplo Arm		1AgMM Related/Unrelated Donors		MUD Donor		Second Transplant		Myelofibrosis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	84/84 (100%)		51/51 (100%)		21/21 (100%)		6/6 (100%)		3/3 (100%)
Blood and lymphatic system disorders
Autoimmune hemolytic anemia	1/84 (1.2%)		0/51 (0%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Delayed Engraftment	3/84 (3.6%)		3/51 (5.9%)		1/21 (4.8%)		0/6 (0%)		0/3 (0%)
Elevated WBC	1/84 (1.2%)		0/51 (0%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Graft failure	1/84 (1.2%)		0/51 (0%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Secondary graft failure	11/84 (13.1%)		0/51 (0%)		3/21 (14.3%)		1/6 (16.7%)		1/3 (33.3%)
Thrombocytopenia	0/84 (0%)		4/51 (7.8%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
TMA	1/84 (1.2%)		2/51 (3.9%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Cardiac disorders
Cardiomyopathy	3/84 (3.6%)		3/51 (5.9%)		2/21 (9.5%)		1/6 (16.7%)		1/3 (33.3%)
Endocarditis	1/84 (1.2%)		0/51 (0%)		0/21 (0%)		1/6 (16.7%)		0/3 (0%)
Hypertension	18/84 (21.4%)		19/51 (37.3%)		5/21 (23.8%)		0/6 (0%)		2/3 (66.7%)
Orthostatic hypotension	1/84 (1.2%)		1/51 (2%)		1/21 (4.8%)		1/6 (16.7%)		0/3 (0%)
Supraventricular tachycardia	0/84 (0%)		2/51 (3.9%)		1/21 (4.8%)		0/6 (0%)		0/3 (0%)
Tachycardia	1/84 (1.2%)		0/51 (0%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Eye disorders
Chronic Ocular GVHD	1/84 (1.2%)		0/51 (0%)		0/21 (0%)		1/6 (16.7%)		0/3 (0%)
Gastrointestinal disorders
Ascites	2/84 (2.4%)		0/51 (0%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
C difficile colitis	2/84 (2.4%)		0/51 (0%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Chorioretinitis	0/84 (0%)		1/51 (2%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Chronic GI GVHD	4/84 (4.8%)		3/51 (5.9%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Colitis	0/84 (0%)		1/51 (2%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Diarrhea	55/84 (65.5%)		33/51 (64.7%)		15/21 (71.4%)		4/6 (66.7%)		1/3 (33.3%)
GI bleed	0/84 (0%)		1/51 (2%)		0/21 (0%)		0/6 (0%)		1/3 (33.3%)
GI GVHD	14/84 (16.7%)		9/51 (17.6%)		6/21 (28.6%)		2/6 (33.3%)		2/3 (66.7%)
GI pain	2/84 (2.4%)		1/51 (2%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Mucositis	41/84 (48.8%)		30/51 (58.8%)		9/21 (42.9%)		4/6 (66.7%)		2/3 (66.7%)
Nausea	84/84 (100%)		51/51 (100%)		21/21 (100%)		6/6 (100%)		2/3 (66.7%)
Upper GI GVHD	26/84 (31%)		11/51 (21.6%)		8/21 (38.1%)		3/6 (50%)		1/3 (33.3%)
General disorders
Chronic Oral GVHD	3/84 (3.6%)		0/51 (0%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Headache	8/84 (9.5%)		2/51 (3.9%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Metabolic encephalopathy	0/84 (0%)		3/51 (5.9%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Hepatobiliary disorders
Chronic Liver GVHD	1/84 (1.2%)		0/51 (0%)		1/21 (4.8%)		0/6 (0%)		0/3 (0%)
Elevated ALK Phosphatase	7/84 (8.3%)		5/51 (9.8%)		3/21 (14.3%)		0/6 (0%)		0/3 (0%)
Elevated ALT	19/84 (22.6%)		12/51 (23.5%)		5/21 (23.8%)		3/6 (50%)		0/3 (0%)
Elevated AST	0/84 (0%)		1/51 (2%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Elevated bilirubin	21/84 (25%)		20/51 (39.2%)		3/21 (14.3%)		1/6 (16.7%)		2/3 (66.7%)
Liver GVHD	0/84 (0%)		1/51 (2%)		1/21 (4.8%)		0/6 (0%)		1/3 (33.3%)
Veno occlusive disease	0/84 (0%)		2/51 (3.9%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Infections and infestations
CMV chorioretinitis	1/84 (1.2%)		0/51 (0%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Disseminated toxoplasmosis	1/84 (1.2%)		0/51 (0%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Idiopathic pneumonitis	1/84 (1.2%)		0/51 (0%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Bacterial infection	65/84 (77.4%)		38/51 (74.5%)		19/21 (90.5%)		2/6 (33.3%)		2/3 (66.7%)
Fungal infection	5/84 (6%)		6/51 (11.8%)		1/21 (4.8%)		0/6 (0%)		0/3 (0%)
Viral Infection	70/84 (83.3%)		36/51 (70.6%)		17/21 (81%)		5/6 (83.3%)		3/3 (100%)
Neutropenic fever	38/84 (45.2%)		16/51 (31.4%)		1/21 (4.8%)		2/6 (33.3%)		2/3 (66.7%)
Neutropenic Typhlitis	1/84 (1.2%)		2/51 (3.9%)		1/21 (4.8%)		0/6 (0%)		1/3 (33.3%)
HSV oral infection	1/84 (1.2%)		0/51 (0%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Investigations
Fever	13/84 (15.5%)		5/51 (9.8%)		2/21 (9.5%)		1/6 (16.7%)		0/3 (0%)
Fluid overload	61/84 (72.6%)		29/51 (56.9%)		18/21 (85.7%)		5/6 (83.3%)		3/3 (100%)
Infusion reaction	1/84 (1.2%)		0/51 (0%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Musculoskeletal and connective tissue disorders
Bone pain	0/84 (0%)		0/51 (0%)		1/21 (4.8%)		0/6 (0%)		0/3 (0%)
Myopathy	0/84 (0%)		1/51 (2%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Nervous system disorders
Altered mental status	4/84 (4.8%)		3/51 (5.9%)		2/21 (9.5%)		0/6 (0%)		0/3 (0%)
Seizure	1/84 (1.2%)		0/51 (0%)		1/21 (4.8%)		0/6 (0%)		0/3 (0%)
Tremors	2/84 (2.4%)		1/51 (2%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Renal and urinary disorders
Acute renal failure	4/84 (4.8%)		5/51 (9.8%)		3/21 (14.3%)		0/6 (0%)		1/3 (33.3%)
BK virus associated hemorrhagic cystitis	37/84 (44%)		18/51 (35.3%)		6/21 (28.6%)		4/6 (66.7%)		1/3 (33.3%)
Hemorrhagic cystitis	5/84 (6%)		4/51 (7.8%)		1/21 (4.8%)		0/6 (0%)		1/3 (33.3%)
Renal insufficiency	11/84 (13.1%)		5/51 (9.8%)		2/21 (9.5%)		2/6 (33.3%)		3/3 (100%)
Respiratory, thoracic and mediastinal disorders
Bronchitis	1/84 (1.2%)		1/51 (2%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
DAH	0/84 (0%)		1/51 (2%)		1/21 (4.8%)		0/6 (0%)		0/3 (0%)
Pleural effusion	1/84 (1.2%)		2/51 (3.9%)		1/21 (4.8%)		0/6 (0%)		0/3 (0%)
Pneumonitis	16/84 (19%)		5/51 (9.8%)		8/21 (38.1%)		0/6 (0%)		0/3 (0%)
Fungal pneumonia	4/84 (4.8%)		5/51 (9.8%)		1/21 (4.8%)		0/6 (0%)		0/3 (0%)
Pulmonary edema	1/84 (1.2%)		1/51 (2%)		0/21 (0%)		1/6 (16.7%)		0/3 (0%)
Shortness of Breath	1/84 (1.2%)		2/51 (3.9%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Skin and subcutaneous tissue disorders
Cellulitis	2/84 (2.4%)		1/51 (2%)		1/21 (4.8%)		0/6 (0%)		0/3 (0%)
Chemo Burn	1/84 (1.2%)		0/51 (0%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Chronic Skin GVHD	7/84 (8.3%)		2/51 (3.9%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Hand/Foot syndrome	4/84 (4.8%)		1/51 (2%)		0/21 (0%)		0/6 (0%)		0/3 (0%)
Skin rash	5/84 (6%)		7/51 (13.7%)		1/21 (4.8%)		0/6 (0%)		0/3 (0%)
Skin GVHD	21/84 (25%)		17/51 (33.3%)		6/21 (28.6%)		4/6 (66.7%)		0/3 (0%)

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.