Combination Chemotherapy and Donor Stem Cell Transplant in Treating Patients With Aplastic Anemia or Hematologic Cancer

• Sponsor: Roswell Park Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00003816
• Collaborator: (none)
• Enrollment: 361
• Location: 1
• Arms: 9
• Actual Duration (Months): 248.7
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

RATIONALE: Giving chemotherapy drugs and total-body irradiation before a donor stem cell helps stop the growth of cancer or abnormal cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. It is not yet known which combination chemotherapy regimen is most effective when given before a donor stem cell transplant in treating aplastic anemia or hematologic cancer.

PURPOSE: This phase II/III trial is studying different combination chemotherapy regimens to compare how well they work when given before donor stem cell transplant in treating patients with aplastic anemia or hematologic cancer.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases; Nonmalignant Neoplasm; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific	Biological: anti-thymocyte globulin; Drug: busulfan; Drug: carboplatin; Drug: cyclophosphamide; Drug: etoposide; Drug: fludarabine phosphate; Drug: melphalan; Drug: thiotepa; Radiation: total-body irradiation	Phase 2/Phase 3

Detailed Description

OBJECTIVES:

• Compare the morbidity, mortality, and overall outcome of patients with severe aplastic anemia or hematologic malignancy treated with standard vs novel conditioning regimens followed by allogeneic stem cell transplantation.

• Examine the influence of donor histocompatibility on outcome by comparing matched/related, mismatched/related (with or without T-cell depletion), and matched/unrelated transplants with stratification for type of preparative regimen.

• Ensure that patients with uncommon diagnoses will be treated in a uniform fashion with the best therapy available.

OUTLINE: Patients are stratified according to risk of relapse (standard-risk: acute leukemia in first complete remission, chronic myelogenous leukemia in first chronic phase, lymphoma in sensitive first relapse or second remission, primary or untreated myelodysplastic syndromes, or untreated severe aplastic anemia vs high-risk: all others).

Patients are assigned to one of the following conditioning regimens based on diagnosis, risk of relapse, and donor relatedness:

• Regimen 1: Patients receive busulfan IV over 2 hours every 6 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2.

• Regimen 2: Patients receive cyclophosphamide IV over 2 hours on days -5 to -2 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -3.

• Regimen 3: Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and total-body irradiation (TBI) twice daily on days -3 to -1.

• Regimen 4: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and melphalan IV over 1 hour on days -3 and -2.

• Regimen 5: Patients receive etoposide IV over 26 hours beginning on day -5, cyclophosphamide IV over 2 hours on day -4, and TBI twice daily on days -3 to -1.

• Regimen 6: Patients receive cyclophosphamide IV over 24 hours, carboplatin IV over 24 hours, and thiotepa IV over 24 hours on days -7 to -4.

• Regimen 7: Patients receive fludarabine IV over 30 minutes on days -5 to -1 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -2.

• Regimen 8: Patients receive cyclophosphamide IV over 2 hours on days -5 and -4, TBI twice daily on days -3 to -1, and anti-thymocyte globulin IV over 4-8 hours on days -3 to -1.

• Regimen 9: Patients receive busulfan IV over 2 hours every 6 hours and anti-thymocyte globulin IV over 4-8 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2.

All patients then receive donor stem cell infusions on day 0. Some patients may undergo involved-field radiotherapy 4-8 weeks after transplant.

Patients will be taken off study after a minimum of 4 years of follow up.

PROJECTED ACCRUAL: At least 405 patients will be accrued for this study within 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 361 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Allogeneic Blood or Marrow Transplantation for Hematologic Malignancy and Aplastic Anemia
• Actual Study Start Date: Oct 19, 1998
• Actual Primary Completion Date: Jul 12, 2019
• Actual Study Completion Date: Jul 12, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Regimen 1 Patients receive busulfan IV over 2 hours every 6 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2.	Drug: busulfan; Given IV; Drug: cyclophosphamide; Given IV
Experimental: Regimen 2 Patients receive cyclophosphamide IV over 2 hours on days -5 to -2 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -3.	Biological: anti-thymocyte globulin; Given IV; Drug: cyclophosphamide; Given IV
Experimental: Regimen 3 Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and total-body irradiation (TBI) twice daily on days -3 to -1.	Drug: cyclophosphamide; Given IV; Radiation: total-body irradiation; Given twice daily for 3 days
Experimental: Regimen 4 Patients receive fludarabine IV over 30 minutes on days -6 to -2 and melphalan IV over 1 hour on days -3 and -2.	Drug: fludarabine phosphate; Given IV; Drug: melphalan; Given IV
Experimental: Regimen 5 Patients receive etoposide IV over 26 hours beginning on day -5, cyclophosphamide IV over 2 hours on day -4, and TBI twice daily on days -3 to -1.	Drug: cyclophosphamide; Given IV; Drug: etoposide; Given IV; Radiation: total-body irradiation; Given twice daily for 3 days
Experimental: Regimen 6 Patients receive cyclophosphamide IV over 24 hours, carboplatin IV over 24 hours, and thiotepa IV over 24 hours on days -7 to -4.	Drug: carboplatin; Given IV; Drug: cyclophosphamide; Given IV; Drug: thiotepa; Given IV
Experimental: Regimen 7 Patients receive fludarabine IV over 30 minutes on days -5 to -1 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -2.	Biological: anti-thymocyte globulin; Given IV; Drug: fludarabine phosphate; Given IV
Experimental: Regimen 8 Patients receive cyclophosphamide IV over 2 hours on days -5 and -4, TBI twice daily on days -3 to -1, and anti-thymocyte globulin IV over 4-8 hours on days -3 to -1.	Biological: anti-thymocyte globulin; Given IV; Drug: cyclophosphamide; Given IV; Radiation: total-body irradiation; Given twice daily for 3 days
Experimental: Regimen 9 Patients receive busulfan IV over 2 hours every 6 hours and anti-thymocyte globulin IV over 4-8 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2.	Biological: anti-thymocyte globulin; Given IV; Drug: busulfan; Given IV; Drug: cyclophosphamide; Given IV

Outcome Measures

Primary Outcome Measures

1. CR Rate [day 100]

   Rate of Complete Remission by Day +100

Secondary Outcome Measures

1. Toxicity/TRM at Day 100 [Day +100]

   Death due to treatment related causes before day +100 after BMT

2. 4 Year PFS [4 years]

   progression free survival estimate at 4 years post BMT (events are disease progression/relapse and death due to any cause)

3. 4 yr OS [4-year]

   Overall survival estimate at 4 years post BMT

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Diagnosis of one of the following:

• Severe aplastic anemia as defined by either of the following:

• Marrow cellularity (< 25% [or 25-50% cellularity with < 30% of remaining cells hematopoietic in origin])

• At least 2 of the following abnormal peripheral blood counts:

• Reticulocyte count < 1% (corrected for hematocrit)

• Platelet count < 20,000/mm^3

• Neutrophil count < 500/mm^3

• Histologically confirmed hematologic malignancy, including any of the following:

• Acute leukemia

• Resistant or recurrent disease after combination chemotherapy with at least one standard regimen OR in first remission and at high risk of relapse

• Acute myeloid leukemia (AML) (antecedent myelodysplastic syndromes [MDS], secondary AML, or high-risk cytogenetic abnormalities)

• Acute lymphoblastic leukemia (ALL) (high-risk cytogenetic abnormalities)

• Chronic myeloid leukemia (CML)

• Chronic phase, accelerated phase, or blast phase

• Myeloproliferative disorders or MDS, including any of the following:

• Myelofibrosis

• Polycythemia vera*

• Essential thrombocythemia*

• Refractory anemia

• Refractory anemia with excess blasts

• Refractory anemia with excess blasts in transformation

• Chronic myelomonocytic leukemia NOTE: * Only if transformed to AML or MDS

• Lymphoproliferative disease

• Recurrent or persistent, symptomatic disease after first-line chemotherapy, including any of the following:

• Chronic lymphocytic leukemia (CLL) (≥ 20% marrow involvement)

• Waldenstrom macroglobulinemia

• Low-grade non-Hodgkin lymphoma

• Intermediate or high-grade non-Hodgkin lymphoma, meeting 1 of the following criteria:

• Resistant or recurrent disease after combination chemotherapy with one standard regimen

• Lymphoblastic lymphoma or small noncleaved cell lymphoma in first remission and at high risk of relapse

• CNS disease

• Bone marrow disease and LDH greater than 300

• Solid tumor that would otherwise be treated on RPCI-DS-9115 (or equivalent autologous stem transplant protocol) AND has a syngeneic donor

• Autologous bone marrow transplant not possible (or desirable) due to 1 of the following:

• History of marrow tumor

• Inadequate marrow dose

• Abnormal marrow histology or function prior to storage

• Thrombocytopenia or leukopenia

• Marrow cellularity < 20%

• Histocompatible donor identified

• Well-matched donor, as defined by 1 of the following:

• Family member matched for 5 or 6 HLA specificities (A, B, DR)*

• Unrelated donor meeting compatibility criteria of the National Marrow Donor Program (matched for HLA A, B, and DRB1 antigens)*

• Identical twin sibling

• If a compatible cord blood donor is identified and there is no suitable unrelated donor available, patient may receive cord blood transplant NOTE: *Patients ≤ 25 years of age may be singly mismatched at the A or B loci

NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age:

• 4 to 70

Performance status:

• Zubrod 0-2 OR

• Karnofsky 70-100%

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Bilirubin < 3 times normal (unless due to disease)

• Alkaline phosphatase < 3 times normal (unless due to disease)

• SGOT < 3 times normal (unless due to disease)

• Hepatitis B surface antigen negative

• No severe hepatic disease that would preclude study participation

Renal:

• Creatinine normal

• Creatinine clearance ≥ 50 mL/min

• No severe renal disease that would preclude study participation

Cardiovascular:

• Cardiac ventricular ejection fraction ≥ 50% by MUGA or echocardiogram

• No uncontrolled or severe cardiovascular disease (e.g., myocardial infarction, congestive heart failure, symptomatic angina, life threatening arrhythmia, or hypertension within the past 6 months)

Pulmonary:

• DLCO or DLVA ≥ 50% predicted (corrected for hemoglobin or alveolar ventilation)

Other:

• No serious concurrent medical or psychiatric illness

• No other serious organ dysfunction (unless due to underlying disease), including the following:

• Uncontrolled bacterial, viral, or fungal infection

• Uncontrolled peptic ulcer disease

• Uncontrolled diabetes mellitus

• HIV negative

• Cytomegalovirus status known

• Not pregnant

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics

• Pretransplant cytoreductive chemotherapy allowed for patients with relapsed or refractory disease

Endocrine therapy:

• Not specified

Radiotherapy:

• Not eligible for total-body irradiation if prior radiotherapy exceeded the following limits:

• Mediastinum: 3,600 cGy

• Heart: 3,600 cGy

• Whole lungs: 1,200 cGy

• Small bowel: 3,600 cGy

• Kidneys: 1,200 cGy

• Whole liver: 1,600 cGy

• Cranial spinal: 3,600 cGy

• Brain: 4,000 cGy

• Retina: 4,000 cGy

Surgery:

• Not specified

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001

Sponsors and Collaborators

• Roswell Park Cancer Institute

Investigators

• Study Chair: Philip L. McCarthy, MD, Roswell Park Cancer Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 22, 2018

More Information

Publications

None provided.

• Responsible Party: Roswell Park Cancer Institute
• ClinicalTrials.gov Identifier: NCT00003816
• Other Study ID Numbers: RP 98-15; RP 98-15
• First Posted: Jan 27, 2003
• Last Update Posted: Aug 13, 2021
• Last Verified: Jul 1, 2021

• Keywords provided by Roswell Park Cancer Institute: recurrent childhood acute lymphoblastic leukemia; recurrent cutaneous T-cell non-Hodgkin lymphoma; Burkitt lymphoma; Waldenstrom macroglobulinemia; recurrent childhood lymphoblastic lymphoma; recurrent childhood acute myeloid leukemia; recurrent adult acute myeloid leukemia; recurrent adult acute lymphoblastic leukemia; relapsing chronic myelogenous leukemia; refractory chronic lymphocytic leukemia; chronic phase chronic myelogenous leukemia; accelerated phase chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia; adult acute myeloid leukemia in remission; adult acute lymphoblastic leukemia in remission; childhood acute myeloid leukemia in remission; childhood acute lymphoblastic leukemia in remission; polycythemia vera; essential thrombocythemia; refractory anemia; refractory anemia with excess blasts; refractory anemia with excess blasts in transformation; chronic myelomonocytic leukemia; T-cell large granular lymphocyte leukemia; acute undifferentiated leukemia; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent adult lymphoblastic lymphoma; recurrent adult Burkitt lymphoma; recurrent adult T-cell leukemia/lymphoma; secondary acute myeloid leukemia; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; prolymphocytic leukemia; intraocular lymphoma; recurrent childhood small noncleaved cell lymphoma; recurrent childhood large cell lymphoma; recurrent mantle cell lymphoma; angioimmunoblastic T-cell lymphoma; anaplastic large cell lymphoma; recurrent mycosis fungoides/Sezary syndrome; primary myelofibrosis; childhood chronic myelogenous leukemia; atypical chronic myeloid leukemia; myelodysplastic/myeloproliferative disease, unclassifiable; recurrent marginal zone lymphoma; recurrent small lymphocytic lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; adult acute myeloid leukemia with t(8;21)(q22;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with t(15;17)(q22;q12); childhood myelodysplastic syndromes; aplastic anemia; unspecified adult solid tumor, protocol specific; unspecified childhood solid tumor, protocol specific
• Additional relevant MeSH terms: Lymphoma; Neoplasms; Leukemia; Preleukemia; Anemia; Myelodysplastic Syndromes; Anemia, Aplastic; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome; Cyclophosphamide; Melphalan; Busulfan; Thiotepa; Carboplatin; Fludarabine; Fludarabine phosphate; Etoposide; Antilymphocyte Serum

Study Results

Participant Flow

Arm/Group Title	BuCy	CyTBI	FluMel	VpCyTBI	Other
Arm/Group Description	Patients receive busulfan IV over 2 hours every 6 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2. busulfan: Given IV cyclophosphamide: Given IV	Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and total-body irradiation (TBI) twice daily on days -3 to -1. cyclophosphamide: Given IV total-body irradiation: Given twice daily for 3 days	Patients receive fludarabine IV over 30 minutes on days -6 to -2 and melphalan IV over 1 hour on days -3 and -2. fludarabine phosphate: Given IV melphalan: Given IV	Patients receive etoposide IV over 26 hours beginning on day -5, cyclophosphamide IV over 2 hours on day -4, and TBI twice daily on days -3 to -1. cyclophosphamide: Given IV etoposide: Given IV total-body irradiation: Given twice daily for 3 days	Patients receive cyclophosphamide IV over 2 hours on days -5 and -4, TBI twice daily on days -3 to -1, and anti-thymocyte globulin IV over 4-8 hours on days -3 to -1. OR Patients receive cyclophosphamide IV over 2 hours on days -5 to -2 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -3. OR Patients receive cyclophosphamide IV over 24 hours, carboplatin IV over 24 hours, and thiotepa IV over 24 hours on days -7 to -4. OR Patients receive fludarabine IV over 30 minutes on days -5 to -1 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -2. OR Patients receive busulfan IV over 2 hours every 6 hours and anti-thymocyte globulin IV over 4-8 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2.
Period Title: Overall Study
STARTED	55	69	199	23	15
COMPLETED	55	69	199	23	15
NOT COMPLETED	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	BuCy	CyTBI	FluMel	VpCyTBI	Other	Total
Arm/Group Description	Patients receive busulfan IV over 2 hours every 6 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2. busulfan: Given IV cyclophosphamide: Given IV	Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and total-body irradiation (TBI) twice daily on days -3 to -1. cyclophosphamide: Given IV total-body irradiation: Given twice daily for 3 days	Patients receive fludarabine IV over 30 minutes on days -6 to -2 and melphalan IV over 1 hour on days -3 and -2. fludarabine phosphate: Given IV melphalan: Given IV	Patients receive etoposide IV over 26 hours beginning on day -5, cyclophosphamide IV over 2 hours on day -4, and TBI twice daily on days -3 to -1. cyclophosphamide: Given IV etoposide: Given IV total-body irradiation: Given twice daily for 3 days	Patients receive cyclophosphamide IV over 2 hours on days -5 to -2 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -3. OR Patients receive cyclophosphamide IV over 24 hours, carboplatin IV over 24 hours, and thiotepa IV over 24 hours on days -7 to -4. OR Patients receive fludarabine IV over 30 minutes on days -5 to -1 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -2. OR Patients receive cyclophosphamide IV over 2 hours on days -5 and -4, TBI twice daily on days -3 to -1, and anti-thymocyte globulin IV over 4-8 hours on days -3 to -1. OR Patients receive busulfan IV over 2 hours every 6 hours and anti-thymocyte globulin IV over 4-8 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2.	Total of all reporting groups
Overall Participants	55	69	199	23	15	361
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	46	28	48	37	41	44
Sex: Female, Male (Count of Participants)
Female	24 43.6%	24 34.8%	80 40.2%	7 30.4%	4 26.7%	139 38.5%
Male	31 56.4%	45 65.2%	119 59.8%	16 69.6%	11 73.3%	222 61.5%
Race/Ethnicity, Customized (Count of Participants)
Non-Hispanic White	53 96.4%	68 98.6%	188 94.5%	20 87%	12 80%	341 94.5%
Non-Hispanic African American	0 0%	0 0%	8 4%	1 4.3%	3 20%	12 3.3%
Non-Hispanic Asian	1 1.8%	1 1.4%	0 0%	1 4.3%	0 0%	3 0.8%
Hispanic, White	0 0%	0 0%	3 1.5%	0 0%	0 0%	3 0.8%
Non-Hispanic Native Am	1 1.8%	0 0%	0 0%	1 4.3%	0 0%	2 0.6%
Region of Enrollment (participants) [Number]
United States	55 100%	69 100%	199 100%	23 100%	15 100%	361 100%
Disease (Count of Participants)
Acute myeloid leukemia	17 30.9%	25 36.2%	89 44.7%	13 56.5%	3 20%	147 40.7%
Acute lymphoblastic leukemia	2 3.6%	30 43.5%	16 8%	5 21.7%	1 6.7%	54 15%
Chronic myeloid or lymphocytic leukemia	14 25.5%	7 10.1%	14 7%	0 0%	2 13.3%	37 10.2%
Hodgkin or Non-Hodgkin lymphoma or multiple myeloma	6 10.9%	2 2.9%	56 28.1%	4 17.4%	4 26.7%	72 19.9%
Myelodysplastic syndrome or myeloproliferative disorder	15 27.3%	3 4.3%	23 11.6%	1 4.3%	1 6.7%	43 11.9%
Severe Aplastic anemia	1 1.8%	2 2.9%	1 0.5%	0 0%	3 20%	7 1.9%
Solid Tumor	0 0%	0 0%	0 0%	0 0%	1 6.7%	1 0.3%
Risk group (Count of Participants)
Standard	32 58.2%	42 60.9%	73 36.7%	10 43.5%	4 26.7%	161 44.6%
High	23 41.8%	27 39.1%	126 63.3%	13 56.5%	11 73.3%	200 55.4%

Outcome Measures

1. Primary Outcome

Title	CR Rate
Description	Rate of Complete Remission by Day +100
Time Frame	day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BuCy	CyTBI	FluMel	VpCyTBI	Other
Arm/Group Description	Patients receive busulfan IV over 2 hours every 6 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2. busulfan: Given IV cyclophosphamide: Given IV	Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and total-body irradiation (TBI) twice daily on days -3 to -1. cyclophosphamide: Given IV total-body irradiation: Given twice daily for 3 days	Patients receive fludarabine IV over 30 minutes on days -6 to -2 and melphalan IV over 1 hour on days -3 and -2. fludarabine phosphate: Given IV melphalan: Given IV	Patients receive etoposide IV over 26 hours beginning on day -5, cyclophosphamide IV over 2 hours on day -4, and TBI twice daily on days -3 to -1. cyclophosphamide: Given IV etoposide: Given IV total-body irradiation: Given twice daily for 3 days	Patients receive cyclophosphamide IV over 2 hours on days -5 and -4, TBI twice daily on days -3 to -1, and anti-thymocyte globulin IV over 4-8 hours on days -3 to -1. OR Patients receive cyclophosphamide IV over 2 hours on days -5 to -2 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -3. OR Patients receive cyclophosphamide IV over 24 hours, carboplatin IV over 24 hours, and thiotepa IV over 24 hours on days -7 to -4. OR Patients receive fludarabine IV over 30 minutes on days -5 to -1 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -2. OR Patients receive busulfan IV over 2 hours every 6 hours and anti-thymocyte globulin IV over 4-8 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2.
Measure Participants	55	69	199	23	15
Count of Participants [Participants]	42 76.4%	55 79.7%	134 67.3%	18 78.3%	7 46.7%

2. Secondary Outcome

Title	Toxicity/TRM at Day 100
Description	Death due to treatment related causes before day +100 after BMT
Time Frame	Day +100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BuCy	CyTBI	FluMel	VpCyTBI	Other
Arm/Group Description	Patients receive busulfan IV over 2 hours every 6 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2. busulfan: Given IV cyclophosphamide: Given IV	Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and total-body irradiation (TBI) twice daily on days -3 to -1. cyclophosphamide: Given IV total-body irradiation: Given twice daily for 3 days	Patients receive fludarabine IV over 30 minutes on days -6 to -2 and melphalan IV over 1 hour on days -3 and -2. fludarabine phosphate: Given IV melphalan: Given IV	Patients receive etoposide IV over 26 hours beginning on day -5, cyclophosphamide IV over 2 hours on day -4, and TBI twice daily on days -3 to -1. cyclophosphamide: Given IV etoposide: Given IV total-body irradiation: Given twice daily for 3 days	Patients receive cyclophosphamide IV over 2 hours on days -5 and -4, TBI twice daily on days -3 to -1, and anti-thymocyte globulin IV over 4-8 hours on days -3 to -1. OR Patients receive cyclophosphamide IV over 2 hours on days -5 to -2 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -3. OR Patients receive cyclophosphamide IV over 24 hours, carboplatin IV over 24 hours, and thiotepa IV over 24 hours on days -7 to -4. OR Patients receive fludarabine IV over 30 minutes on days -5 to -1 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -2. OR Patients receive busulfan IV over 2 hours every 6 hours and anti-thymocyte globulin IV over 4-8 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2.
Measure Participants	55	69	199	23	15
Count of Participants [Participants]	3 5.5%	4 5.8%	31 15.6%	4 17.4%	4 26.7%

3. Secondary Outcome

Title	4 Year PFS
Description	progression free survival estimate at 4 years post BMT (events are disease progression/relapse and death due to any cause)
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BuCy	CyTBI	FluMel	VpCyTBI	Other
Arm/Group Description	Patients receive busulfan IV over 2 hours every 6 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2. busulfan: Given IV cyclophosphamide: Given IV	Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and total-body irradiation (TBI) twice daily on days -3 to -1. cyclophosphamide: Given IV total-body irradiation: Given twice daily for 3 days	Patients receive fludarabine IV over 30 minutes on days -6 to -2 and melphalan IV over 1 hour on days -3 and -2. fludarabine phosphate: Given IV melphalan: Given IV	Patients receive etoposide IV over 26 hours beginning on day -5, cyclophosphamide IV over 2 hours on day -4, and TBI twice daily on days -3 to -1. cyclophosphamide: Given IV etoposide: Given IV total-body irradiation: Given twice daily for 3 days	Patients receive cyclophosphamide IV over 2 hours on days -5 and -4, TBI twice daily on days -3 to -1, and anti-thymocyte globulin IV over 4-8 hours on days -3 to -1. OR Patients receive cyclophosphamide IV over 2 hours on days -5 to -2 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -3. OR Patients receive cyclophosphamide IV over 24 hours, carboplatin IV over 24 hours, and thiotepa IV over 24 hours on days -7 to -4. OR Patients receive fludarabine IV over 30 minutes on days -5 to -1 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -2. OR Patients receive busulfan IV over 2 hours every 6 hours and anti-thymocyte globulin IV over 4-8 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2.
Measure Participants	55	69	199	23	15
Number (95% Confidence Interval) [percentage of participants]	49.1 89.3%	52.2 75.7%	33.2 16.7%	26.1 113.5%	40 266.7%

4. Secondary Outcome

Title	4 yr OS
Description	Overall survival estimate at 4 years post BMT
Time Frame	4-year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BuCy	CyTBI	FluMel	VpCyTBI	Other
Arm/Group Description	Patients receive busulfan IV over 2 hours every 6 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2. busulfan: Given IV cyclophosphamide: Given IV	Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and total-body irradiation (TBI) twice daily on days -3 to -1. cyclophosphamide: Given IV total-body irradiation: Given twice daily for 3 days	Patients receive fludarabine IV over 30 minutes on days -6 to -2 and melphalan IV over 1 hour on days -3 and -2. fludarabine phosphate: Given IV melphalan: Given IV	Patients receive etoposide IV over 26 hours beginning on day -5, cyclophosphamide IV over 2 hours on day -4, and TBI twice daily on days -3 to -1. cyclophosphamide: Given IV etoposide: Given IV total-body irradiation: Given twice daily for 3 days	Patients receive cyclophosphamide IV over 2 hours on days -5 and -4, TBI twice daily on days -3 to -1, and anti-thymocyte globulin IV over 4-8 hours on days -3 to -1. OR Patients receive cyclophosphamide IV over 2 hours on days -5 to -2 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -3. OR Patients receive cyclophosphamide IV over 24 hours, carboplatin IV over 24 hours, and thiotepa IV over 24 hours on days -7 to -4. OR Patients receive fludarabine IV over 30 minutes on days -5 to -1 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -2. OR Patients receive busulfan IV over 2 hours every 6 hours and anti-thymocyte globulin IV over 4-8 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2.
Measure Participants	55	69	199	23	15
Number (95% Confidence Interval) [percentage of participants]	56.4 102.5%	56.5 81.9%	38.2 19.2%	39.1 170%	53.3 355.3%

Adverse Events

Time Frame	1 year
Arm/Group Title	BuCy		CyTBI		FluMel		VpCyTBI		Other
Arm/Group Description	Patients receive busulfan IV over 2 hours every 6 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2. busulfan: Given IV cyclophosphamide: Given IV		Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and total-body irradiation (TBI) twice daily on days -3 to -1. cyclophosphamide: Given IV total-body irradiation: Given twice daily for 3 days		Patients receive fludarabine IV over 30 minutes on days -6 to -2 and melphalan IV over 1 hour on days -3 and -2. fludarabine phosphate: Given IV melphalan: Given IV		Patients receive etoposide IV over 26 hours beginning on day -5, cyclophosphamide IV over 2 hours on day -4, and TBI twice daily on days -3 to -1. cyclophosphamide: Given IV etoposide: Given IV total-body irradiation: Given twice daily for 3 days		Patients receive cyclophosphamide IV over 2 hours on days -5 and -4, TBI twice daily on days -3 to -1, and anti-thymocyte globulin IV over 4-8 hours on days -3 to -1. OR Patients receive cyclophosphamide IV over 2 hours on days -5 to -2 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -3. OR Patients receive cyclophosphamide IV over 24 hours, carboplatin IV over 24 hours, and thiotepa IV over 24 hours on days -7 to -4. OR Patients receive fludarabine IV over 30 minutes on days -5 to -1 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -2. OR Patients receive busulfan IV over 2 hours every 6 hours and anti-thymocyte globulin IV over 4-8 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2.
All Cause Mortality
	BuCy		CyTBI		FluMel		VpCyTBI		Other
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/55 (54.5%)		36/69 (52.2%)		150/199 (75.4%)		19/23 (82.6%)		9/15 (60%)
Serious Adverse Events
	BuCy		CyTBI		FluMel		VpCyTBI		Other
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/55 (20%)		10/69 (14.5%)		62/199 (31.2%)		6/23 (26.1%)		4/15 (26.7%)
Investigations
1 yr TRM	11/55 (20%)	11	10/69 (14.5%)	10	62/199 (31.2%)	62	6/23 (26.1%)	6	4/15 (26.7%)	4
Other (Not Including Serious) Adverse Events
	BuCy		CyTBI		FluMel		VpCyTBI		Other
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/55 (45.5%)		35/69 (50.7%)		100/199 (50.3%)		6/23 (26.1%)		9/15 (60%)
Blood and lymphatic system disorders
acute graft-versus-host disease	25/55 (45.5%)	25	35/69 (50.7%)	35	100/199 (50.3%)	100	6/23 (26.1%)	6	9/15 (60%)	9

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.