Donor Stem Cell Transplant in Treating Patients With Relapsed Hematologic Cancer

NCT ID: NCT00053196

Last Updated: 2016-07-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

82 participants

Study Classification

INTERVENTIONAL

Study Start Date

2002-12-31

Study Completion Date

2010-08-31

Brief Summary

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RATIONALE: Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving immunosuppressive therapy after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well donor bone marrow or peripheral stem cell transplant works in treating patients with relapsed hematologic cancer after treatment with chemotherapy and autologous stem cell transplant.

Detailed Description

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OBJECTIVES:

* Determine the feasibility of non-myeloablative allogeneic hematopoietic stem cell transplantation by demonstrating that the risk of treatment-related mortality during the first 6 months is an acceptable rate of less than 40% in patients with relapsed hematologic malignancies after prior high-dose chemotherapy and autologous stem cell transplantation.
* Determine the response rates (disease-specific partial and complete response) in patients treated with this regimen.
* Determine the 6-month and 12-month probabilities of response in patients treated with this regimen.
* Determine the distribution of time-to-progression in patients responding to this regimen.
* Determine the percent donor chimerism in patients treated with this regimen.
* Determine the risk of acute and chronic graft-vs-host disease in patients treated with this regimen.
* Determine the toxic effects of this regimen in these patients.
* Determine the disease-free and overall survival of patients treated with this regimen.

OUTLINE: This is an open-label study.

* Preparative Regimen: Patients receive fludarabine IV over 30 minutes on days -7 to -3 and busulfan IV over 2 hours every 6 hours (for a total of 8 doses) on days -4 and -3.
* Graft vs Host Disease (GVHD) Prophylaxis: Patients who have an HLA-identical donor receive oral (or IV if unable to tolerate oral administration) tacrolimus twice daily on days -1 to 90 followed by a taper\^\* until day 150 and methotrexate IV on days 1, 3, and 6. Patients with a matched related or matched unrelated donor receive oral (or IV if unable to tolerate oral administration) tacrolimus twice daily on days -1 to 180 followed by a taper\^\* as tolerated; methotrexate IV on days 1, 3, 6, and 11; oral mycophenolate mofetil twice daily on days -2 to 60 followed by a taper; and rabbit anti-thymocyte globulin IV over 4-6 hours on days -4 to -1 (for a total of 4 doses).

NOTE: \*Tacrolimus may be tapered on days 60-90 if donor chimerism of CD3+ cells is less than 50% at day 60 or patient has progressive disease

* Allogeneic Stem Cell Transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on days 0 and 1. Patients then receive filgrastim (G-CSF) subcutaneously daily beginning on day 7 and continuing until blood counts recover.
* Donor Lymphocyte Infusion (DLI): After day 180 (or day 210 for patients without an HLA-identical donor), patients with stable or progressive disease and no active GVHD may receive up to 3 DLIs every 8 weeks.

Patients are followed within 2-3 months, every 3 months for 2 years, and then every 6 months for 3 years.

Conditions

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Leukemia Lymphoma Multiple Myeloma Plasma Cell Neoplasm Myelodysplastic Syndromes Myeloproliferative Neoplasms

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Non myeloblative allogeneic transplant

Non myeloblative allogeneic hematopoietic cell transplantation after prior autologous transplantation

Group Type EXPERIMENTAL

anti-thymocyte globulin

Intervention Type BIOLOGICAL

2.5mg/kg/day IV infusion over 6 hrs x 4 doses Days -4 to -1 (for MUD and 9/10 related donor transplants only)

G-CSF

Intervention Type BIOLOGICAL

5 ug/kg/day subQ injection Day 7 until ANC\> 1000/uL for 3 consec days

busulfan

Intervention Type DRUG

0.8mg/kg IV infusion over 2 hrs q 6 hrs x 8 doses Days -4 thru -3

fludarabine phosphate

Intervention Type DRUG

30 mg/sq m/day IVBP over 30 min Days -7 thru -3

methotrexate

Intervention Type DRUG

5 mg/sq m/day IV infusion Days 1, 3, \& 6 for HLA-identical donor transplants and Days 1, 3, 6, \& 11 for MUD \& 9/10 related donor transplants

mycophenolate mofetil

Intervention Type DRUG

15mg/kg PO bid Day -2 to Day 60, then taper as tolerated (for MUD and 9/10 related donor transplants only)

tacrolimus

Intervention Type DRUG

target serum level is 5-10 ng/mL. Start with 0.03mg/kg PO bid Day -1 to Day 90, then taper thru Day 150 for HLA identical donor transplants and Day -1 to Day 180 then taper for MUD and 9/10 related donor transplants

allogeneic cell transplantation

Intervention Type PROCEDURE

2,000,000-8,000,000 CD34+ cells total via infusion Days 0 and 1

allopurinol

Intervention Type DRUG

300 mg/day PO Days -8 thru -1

Interventions

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anti-thymocyte globulin

2.5mg/kg/day IV infusion over 6 hrs x 4 doses Days -4 to -1 (for MUD and 9/10 related donor transplants only)

Intervention Type BIOLOGICAL

G-CSF

5 ug/kg/day subQ injection Day 7 until ANC\> 1000/uL for 3 consec days

Intervention Type BIOLOGICAL

busulfan

0.8mg/kg IV infusion over 2 hrs q 6 hrs x 8 doses Days -4 thru -3

Intervention Type DRUG

fludarabine phosphate

30 mg/sq m/day IVBP over 30 min Days -7 thru -3

Intervention Type DRUG

methotrexate

5 mg/sq m/day IV infusion Days 1, 3, \& 6 for HLA-identical donor transplants and Days 1, 3, 6, \& 11 for MUD \& 9/10 related donor transplants

Intervention Type DRUG

mycophenolate mofetil

15mg/kg PO bid Day -2 to Day 60, then taper as tolerated (for MUD and 9/10 related donor transplants only)

Intervention Type DRUG

tacrolimus

target serum level is 5-10 ng/mL. Start with 0.03mg/kg PO bid Day -1 to Day 90, then taper thru Day 150 for HLA identical donor transplants and Day -1 to Day 180 then taper for MUD and 9/10 related donor transplants

Intervention Type DRUG

allogeneic cell transplantation

2,000,000-8,000,000 CD34+ cells total via infusion Days 0 and 1

Intervention Type PROCEDURE

allopurinol

300 mg/day PO Days -8 thru -1

Intervention Type DRUG

Other Intervention Names

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filgrastim

Eligibility Criteria

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Inclusion Criteria

DISEASE CHARACTERISTICS:

* Histologically confirmed hematologic malignancy, including one of the following:

* Chronic lymphocytic leukemia (CLL)

* Absolute lymphocytosis greater than 5,000/mm\^3
* Lymphocytes must appear morphologically mature with less than 55% prolymphocytes
* Lymphocyte phenotype with expression of CD19 and CD5
* Prolymphocytic leukemia (PLL)

* Morphologically confirmed
* Absolute lymphocytosis greater than 5,000/mm\^3
* More than 55% prolymphocytes
* Non-Hodgkin's lymphoma or Hodgkin's lymphoma

* Any WHO histologic subtype allowed except mantle cell lymphoma
* Core biopsies allowed if they contain adequate tissue for primary diagnosis and immunophenotyping
* No bone marrow biopsy as the sole diagnostic means for follicular lymphoma
* Multiple myeloma

* Active disease requiring treatment
* Durie-Salmon stage I, II, or III
* Acute myeloid leukemia

* Documented control (i.e., less than 10% bone marrow blasts and no circulating blasts)
* Myelodysplastic syndromes

* Documented disease by WHO criteria
* Must have evidence of relapse/progression at least 6 months after prior high-dose chemotherapy with autologous hematopoietic stem cell support
* Absence of CD23 expression for CLL or PLL allowed provided there is no morphologic evidence of mantle cell lymphoma
* Availability of any of the following donor types:

* HLA-identical sibling (6/6)
* 9/10 matched related donor by high-resolution molecular typing at HLA A, B, C, DRB1, and DQB1 loci

* Only a single mismatch at one class I or II allele allowed
* 10/10 matched unrelated donor by high-resolution molecular typing at HLA A, B, C, DRB1, and DQB1 loci
* No syngeneic donors

PATIENT CHARACTERISTICS:

Age

* Under 70

Performance status

* Not specified

Life expectancy

* Not specified

Hematopoietic

* See Disease Characteristics

Hepatic

* Bilirubin no greater than 3 times upper limit of normal (ULN)
* AST no greater than 3 times ULN

Renal

* Creatinine clearance at least 40 mL/min

Cardiovascular

* LVEF at least 30% by MUGA

Pulmonary

* DLCO greater than 40%
* No symptomatic pulmonary disease

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* HIV negative
* No uncontrolled diabetes mellitus
* No active serious infection
* No known hypersensitivity to E. coli-derived products

PRIOR CONCURRENT THERAPY:

Biologic therapy

* See Disease Characteristics

Chemotherapy

* See Disease Characteristics
* More than 4 weeks since prior chemotherapy

Endocrine therapy

* Not specified

Radiotherapy

* More than 4 weeks since prior radiotherapy

Surgery

* More than 4 weeks since prior surgery
Maximum Eligible Age

69 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Asad Bashey, MD, PhD

Role: STUDY_CHAIR

University of California, San Diego

Locations

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Rebecca and John Moores UCSD Cancer Center

La Jolla, California, United States

Site Status

Beebe Medical Center

Lewes, Delaware, United States

Site Status

CCOP - Christiana Care Health Services

Newark, Delaware, United States

Site Status

St. Francis Hospital

Wilmington, Delaware, United States

Site Status

Union Hospital Cancer Center at Union Hospital

Elkton MD, Maryland, United States

Site Status

Siteman Cancer Center at Barnes-Jewish Hospital

St Louis, Missouri, United States

Site Status

Cancer Institute of New Jersey at the Cooper University Hospital - Voorhees

Voorhees Township, New Jersey, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Site Status

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University

Columbus, Ohio, United States

Site Status

Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Massey Cancer Center at Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

Countries

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United States

References

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Bashey A, Owzar K, Johnson JL, Edwards PS, Kelly M, Baxter-Lowe LA, Devine S, Farag S, Hurd D, Ball E, McCarthy P, Lister J, Shea TC, Linker C. Reduced-intensity conditioning allogeneic hematopoietic cell transplantation for patients with hematologic malignancies who relapse following autologous transplantation: a multi-institutional prospective study from the Cancer and Leukemia Group B (CALGB trial 100002). Biol Blood Marrow Transplant. 2011 Apr;17(4):558-65. doi: 10.1016/j.bbmt.2010.07.015. Epub 2010 Jul 30.

Reference Type RESULT
PMID: 20674758 (View on PubMed)

Bashey A, Owzar K, Johnson JL, et al.: Reduced-intensity allogeneic transplantation after failure of autologous transplantation: a prospective multi-center CALGB study. [Abstract] Blood 108 (11): A-3122, 2006.

Reference Type RESULT

Other Identifiers

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U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CALGB-100002

Identifier Type: -

Identifier Source: secondary_id

CDR0000269301

Identifier Type: REGISTRY

Identifier Source: secondary_id

CALGB-100002

Identifier Type: -

Identifier Source: org_study_id

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