AlloHCT From Matched Unrelated Donors in Pts w/ Advanced Hematologic Malignancies & Disorders

NCT ID: NCT00547196

Last Updated: 2024-06-14

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-08-16

Study Completion Date

2024-05-28

Brief Summary

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RATIONALE: Giving chemotherapy with or without total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the 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. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening.

PURPOSE: This clinical trial is studying how well four different chemotherapy regimens given with or without total-body irradiation before umbilical cord blood transplant work in treating patients with relapsed or refractory hematologic cancer.

Detailed Description

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OBJECTIVES:

Primary

* To determine the survival at day 100 of patients with relapsed, refractory, or poor-risk hematological malignancies treated with four different preparative regimens followed by allogeneic hematopoietic stem cell transplantation (HSCT) using two unrelated umbilical cord blood (UCB) units.

Secondary

* To determine the incidence and timing of neutrophil engraftment in patients treated with these regimens.
* To determine the incidence and timing of platelet engraftment in patients treated with these regimens.
* To determine the incidence and severity of acute and chronic graft-versus-host-disease (GVHD) in patients treated with these regimens.
* To determine the survival at day 180 in patients treated with these regimens.
* To determine the disease-free survival in patients treated with these regimens.
* To determine the incidence of primary and secondary engraftment failure in patients treated with these regimens.
* To determine the incidence of transplantation-related complications (e.g., infection, veno-occlusive disease of the liver, or organ toxicity) in these patients.
* To determine the incidence of post-transplantation-related lymphoproliferative disease, secondary myelodysplastic syndromes, or other secondary malignancies in these patients.
* To determine the incidence of relapse in patients treated with these regimens.
* To determine post-transplantation chimerism in patients treated with these regimens.
* To determine immune reconstitution in patients treated with these regimens.

OUTLINE: This is a multicenter study.

* Preparative regimens: Patients are assigned to 1 of 4 preparative regimens.

* Regimen 1 (for patients \< 50 years of age and no contraindication to fractionated total-body irradiation (FTBI): Patients undergo FTBI 2-3 times a day on days -9 to -6 for a total of 11 fractions. Patients also receive cyclophosphamide IV over 2 hours on days -5 and -4 and fludarabine phosphate IV on days -5 to -2.
* Regimen 2 (for patients \< 50 years of age and unable to tolerate FTBI due to prior dose-limiting radiotherapy or significant cardiotoxicity): Patients receive a test dose of busulfan on day -10 and then dose adjusted busulfan IV 3-4 times daily on days -9 to -6, melphalan IV on days -5 and -4, and fludarabine phosphate IV on days -5 to -2.
* Regimen 3\* (for patients unable to tolerate regimen 1 or 2; no age exclusion): Patients receive fludarabine phosphate IV on days -8 to -4 and cyclophosphamide IV over 2 hours on day -3 and undergo TBI (single dose) on day -2.
* Regimen 4\* (for patients unable to tolerate regimen 1 or 2): Patients receive fludarabine phosphate IV on days -7 to -3 and melphalan IV on day -2.

NOTE: \*Treating physician decides the choice between regimen 3 and 4

* Umbilical cord blood (UCB) transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover.
* Graft-versus-host-disease prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).

After completion of study therapy, patients are followed periodically.

Conditions

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Leukemia Lymphoma Myelodysplastic Syndromes

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 I (FTBI, Cyclophosphamide, Fludarabine)

Patients undergo FTBI 2-3 times a day on days -9 to -6 for a total of 11 fractions. Patients also receive cyclophosphamide IV over 2 hours on days -5 and -4 and fludarabine phosphate IV on days -5 to -2. UCB transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover. GVHD prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).

Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

Cyclophosphamide

Intervention Type DRUG

Cyclosporine

Intervention Type DRUG

Fludarabine phosphate

Intervention Type DRUG

Mycophenolate Mofetil

Intervention Type DRUG

allogeneic hematopoietic stem cell transplantation

Intervention Type PROCEDURE

umbilical cord blood transplantation

Intervention Type PROCEDURE

Fractionated total body irradiation

Intervention Type RADIATION

Regimen II (Busulfan, Fludarabine, Melphalan)

Patients receive a test dose of busulfan on day -10 and then dose adjusted busulfan IV 3-4 times daily on days -9 to -6, melphalan IV on days -5 and -4, and fludarabine phosphate IV on days -5 to -2. UCB transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover. GVHD prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).

Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

Busulfan

Intervention Type DRUG

Cyclosporine

Intervention Type DRUG

Fludarabine phosphate

Intervention Type DRUG

Melphalan

Intervention Type DRUG

Mycophenolate Mofetil

Intervention Type DRUG

allogeneic hematopoietic stem cell transplantation

Intervention Type PROCEDURE

umbilical cord blood transplantation

Intervention Type PROCEDURE

Regimen III (TBI, Cyclophosphamide, Fludarabine)

Patients receive fludarabine phosphate IV on days -8 to -4 and cyclophosphamide IV over 2 hours on day -3 and undergo TBI (single dose) on day -2. UCB transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover. GVHD prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).

Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

Cyclophosphamide

Intervention Type DRUG

Cyclosporine

Intervention Type DRUG

Fludarabine phosphate

Intervention Type DRUG

Mycophenolate Mofetil

Intervention Type DRUG

allogeneic hematopoietic stem cell transplantation

Intervention Type PROCEDURE

umbilical cord blood transplantation

Intervention Type PROCEDURE

total-body irradiation

Intervention Type RADIATION

Regimen IV (Fludarabine, Melphalan)

Patients receive fludarabine phosphate IV on days -7 to -3 and melphalan IV on day -2. UCB transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover. GVHD prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).

Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

Cyclosporine

Intervention Type DRUG

Fludarabine phosphate

Intervention Type DRUG

Melphalan

Intervention Type DRUG

Mycophenolate Mofetil

Intervention Type DRUG

allogeneic hematopoietic stem cell transplantation

Intervention Type PROCEDURE

umbilical cord blood transplantation

Intervention Type PROCEDURE

Interventions

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filgrastim

Intervention Type BIOLOGICAL

Busulfan

Intervention Type DRUG

Cyclophosphamide

Intervention Type DRUG

Cyclosporine

Intervention Type DRUG

Fludarabine phosphate

Intervention Type DRUG

Melphalan

Intervention Type DRUG

Mycophenolate Mofetil

Intervention Type DRUG

allogeneic hematopoietic stem cell transplantation

Intervention Type PROCEDURE

umbilical cord blood transplantation

Intervention Type PROCEDURE

total-body irradiation

Intervention Type RADIATION

Fractionated total body irradiation

Intervention Type RADIATION

Other Intervention Names

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Busilvex CTX CsA Fludara Alkeran MMF AlloHCT TBI FTBI

Eligibility Criteria

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Inclusion Criteria

* LVEF \< 50% and \> 40%
* FEV1, FVC, or DLCO \< 50%
* Bilirubin \> 3 mg/dL
* Creatinine \> 2 mg/dL
* Two partially HLA-matched umbilical cord blood (UCB) units available

* HLA-matched minimally at 4 of 6 HLA-A, HLA-B, and -DRB1 loci with the patient

* DRB1 matched by high resolution DNA typing
* HLA-A and HLA-B matched by low resolution at the "serological match" level
* Two pooled units with a nucleated cell number \> 2.5 x 10\^7/kg
* No available HLA-identical sibling or 1 antigen-mismatched related donor
* No available HLA-matched unrelated bone marrow donor

PATIENT CHARACTERISTICS:

* See Disease Characteristics
* Karnofsky performance status (PS) 60-100% OR Lansky PS 60-100% OR Zubrod PS 0-1
* Physiological age 60 or less (at any chronological age)
* Weight \> 50 kg
* Creatinine normal for age OR creatinine clearance by 24-hour urine collection or glomerular filtration rate \> 60 mL/min
* Bilirubin ≤ 1.5 mg/dL
* LVEF ≥ 50%
* DLCO ≥ 60% of predicted
* No HIV-1 infection
* No active uncontrolled infection
* Not pregnant
* Negative pregnancy test
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

* Recovered from prior intensive chemotherapy
Minimum Eligible Age

0 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

City of Hope Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Anna Pawlowska, MD

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

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Banner Good Samaritan Medical Center

Phoenix, Arizona, United States

Site Status

City of Hope Medical Center

Duarte, California, United States

Site Status

Countries

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United States

Other Identifiers

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P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CHNMC-02165

Identifier Type: -

Identifier Source: secondary_id

CDR0000570249

Identifier Type: REGISTRY

Identifier Source: secondary_id

02165

Identifier Type: -

Identifier Source: org_study_id

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