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

NCT ID: NCT00003816

Last Updated: 2021-08-13

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

361 participants

Study Classification

INTERVENTIONAL

Study Start Date

1998-10-19

Study Completion Date

2019-07-12

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Chronic Myeloproliferative Disorders Leukemia Lymphoma Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases Nonmalignant Neoplasm Unspecified Adult Solid Tumor, Protocol Specific Unspecified Childhood Solid Tumor, Protocol Specific

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

busulfan

Intervention Type DRUG

Given IV

cyclophosphamide

Intervention Type DRUG

Given IV

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.

Group Type EXPERIMENTAL

anti-thymocyte globulin

Intervention Type BIOLOGICAL

Given IV

cyclophosphamide

Intervention Type DRUG

Given IV

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.

Group Type EXPERIMENTAL

cyclophosphamide

Intervention Type DRUG

Given IV

total-body irradiation

Intervention Type RADIATION

Given twice daily for 3 days

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.

Group Type EXPERIMENTAL

fludarabine phosphate

Intervention Type DRUG

Given IV

melphalan

Intervention Type DRUG

Given IV

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.

Group Type EXPERIMENTAL

cyclophosphamide

Intervention Type DRUG

Given IV

etoposide

Intervention Type DRUG

Given IV

total-body irradiation

Intervention Type RADIATION

Given twice daily for 3 days

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.

Group Type EXPERIMENTAL

carboplatin

Intervention Type DRUG

Given IV

cyclophosphamide

Intervention Type DRUG

Given IV

thiotepa

Intervention Type DRUG

Given IV

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.

Group Type EXPERIMENTAL

anti-thymocyte globulin

Intervention Type BIOLOGICAL

Given IV

fludarabine phosphate

Intervention Type DRUG

Given IV

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.

Group Type EXPERIMENTAL

anti-thymocyte globulin

Intervention Type BIOLOGICAL

Given IV

cyclophosphamide

Intervention Type DRUG

Given IV

total-body irradiation

Intervention Type RADIATION

Given twice daily for 3 days

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.

Group Type EXPERIMENTAL

anti-thymocyte globulin

Intervention Type BIOLOGICAL

Given IV

busulfan

Intervention Type DRUG

Given IV

cyclophosphamide

Intervention Type DRUG

Given IV

Interventions

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anti-thymocyte globulin

Given IV

Intervention Type BIOLOGICAL

busulfan

Given IV

Intervention Type DRUG

carboplatin

Given IV

Intervention Type DRUG

cyclophosphamide

Given IV

Intervention Type DRUG

etoposide

Given IV

Intervention Type DRUG

fludarabine phosphate

Given IV

Intervention Type DRUG

melphalan

Given IV

Intervention Type DRUG

thiotepa

Given IV

Intervention Type DRUG

total-body irradiation

Given twice daily for 3 days

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

* 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
Minimum Eligible Age

4 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Roswell Park Cancer Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Philip L. McCarthy, MD

Role: STUDY_CHAIR

Roswell Park Cancer Institute

Locations

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Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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RP 98-15

Identifier Type: OTHER

Identifier Source: secondary_id

RP 98-15

Identifier Type: -

Identifier Source: org_study_id

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