DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



Fludarabine Phosphate, Melphalan, Total-Body Irradiation, Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Bone Marrow Failure Disorders

Information source: Roswell Park Cancer Institute
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Accelerated Phase Chronic Myelogenous Leukemia; Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Aplastic Anemia; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Fanconi Anemia; Juvenile Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Paroxysmal Nocturnal Hemoglobinuria; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Splenic Marginal Zone Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Waldenström Macroglobulinemia

Intervention: fludarabine phosphate (Drug); melphalan (Drug); total-body irradiation (Radiation); allogeneic hematopoietic stem cell transplantation (Procedure); anti-thymocyte globulin (Biological)

Phase: N/A

Status: Active, not recruiting

Sponsored by: Roswell Park Cancer Institute

Official(s) and/or principal investigator(s):
Hong Liu, Principal Investigator, Affiliation: Roswell Park Cancer Institute

Summary

This clinical trial is studying how well giving fludarabine phosphate and melphalan together with total-body irradiation followed by donor stem cell transplant works in treating patients with hematologic cancer or bone marrow failure disorders. Giving low doses of chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells or abnormal cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer or abnormal cells (graft-versus-tumor effect)

Clinical Details

Official title: A Pilot Trial Of Reduced Intensity Allogeneic Stem Cell Transplantation With Fludarabine, Melphalan, And Low Dose Total Body Irradiation

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: TRM

Secondary outcome:

Time to engraftment

Time to engraftment

Rate of complete donor chimerism

Rate of complete donor chimerism

Acute GVHD

Chronic GVHD

Safety and toxicity

Overall survival

Detailed description: PRIMARY OBJECTIVES: I. To determine the transplant related mortality (TRM) of this reduced intensity transplantation (RIT) combination in a patient population that is usually not eligible for a full myeloablative allogeneic transplant. SECONDARY OBJECTIVES: I. To evaluate engraftment, safety, clinical response, evidence of graft-versus-malignancy effect/graft-versus-host disease (GVHD) and overall outcomes of treatment with our RIT regimen across a variety of hematological conditions. OUTLINE: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days

- 5 to -2 and melphalan* IV over 30 minutes on day -2. Patients then undergo total-body

irradiation on day - 1 and allogeneic stem cell transplantation on day 0.

Note: *Patients with chromosomal breakage syndromes, such as Fanconi anemia or dyskeratosis

congenita, receive anti-thymocyte globulin IV over 4 hours on day - 4 to -2 instead of

melphalan. After completion of study treatment, patients are followed up periodically.

Eligibility

Minimum age: 3 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Diagnosis of a histology documented hematologic malignancy or marrow disorder

- Bone marrow failure disorders and other non-malignant hematologic or immunologic

disorders:

- Acquired bone marrow failure disorders include aplastic anemia, paroxysmal

nocturnal hemoglobinuria (PNH):

- Primary allogeneic hematopoietic stem cell transplantation (HSCT) is

appropriate for selected patients with severe aplastic anemia; however, patients with aplastic anemia must have failed at least one cycle of standard immunosuppressive therapy with calcineurin inhibitor plus anti-thymocyte globulin (ATG) if a fully-matched donor is not available

- Patients with PNH must have a history of thrombosis related to PNH

- Hereditary bone marrow failure disorders include Fanconi anemia or related

chromosomal breakage syndrome dyskeratosis congenita, Diamond-Blackfan anemia, Shwachman-Diamond syndrome, Kostmann syndrome, congenital amegakaryocytic thrombocytopenia:

- Fanconi anemia or related chromosomal breakage syndrome: positive

chromosome breakage analysis using diepoxybutane (DEB) or mitomycin C if applicable

- Dyskeratosis: diagnosis is supported by using either telomerase reverse

transcriptase (TERC) gene mutation in autosomal dominant Dyskeratosis Congenita or Xlinked DKC1 gene mutation

- Other non-malignant hematologic or immunologic disorders that require

transplantation

- Quantitative or qualitative congenital platelet disorders (including but

not limited to congenital amegakaryocytopenia, absent-radii syndrome, Glanzmann's thrombasthenia)

- Quantitative or qualitative congenital neutrophil disorders (including but

not limited to chronic granulomatous disease, congenital neutropenia)

- Congenital primary immunodeficiencies (including but not limited to Severe

Combined Immunodeficiency Syndrome, Wiskott-Aldrick syndrome, CD40 ligand deficiency, T-cell deficiencies)

- Acute leukemias:

- Subjects must be ineligible for conventional myeloablative transplantation;

- Resistant or recurrent disease after at least one standard combination

chemotherapy regime or first remission patients at high risk of relapse OR First remission patients at high risk of relapse:

- Acute myeloid leukemia (AML)- antecedent myelodysplastic syndrome, secondary

AML, high risk cytogenetic abnormalities or normal cytogenetics with high-risk molecular features (e. g. Flt3-ITD mutation, mixed-lineage leukemia [MLL], wildtype NPM1);

- Acute lymphocytic leukemia (ALL)- high or standard risk ALL

- Chronic Myeloid Leukemia (CML):

- Chronic phase (intolerant or unresponsive to imatinib and/or other tyrosine

kinase inhibitors), second chronic phase or accelerated phase who are ineligible for conventional myeloablative transplantation

- Myeloproliferative and myelodysplastic syndromes (MDS):

- Myelofibrosis (with/without splenectomy) with intermediate to high risk features

- Advanced polycythemia vera not responding to standard therapy

- MDS with an international prostate symptom score (IPSS) score of Int-2 or higher

- MDS with lower IPSS scores Int-1 or less with severe clinical features such as

severe neutropenia or thrombocytopenia or high risk chromosome abnormalities such as monosomy 7

- Secondary massively parallel signature sequencing (MPSS) with any IPSS scores

- Chronic myelomoncytic leukemia

- Lymphoproliferative disease:

- Chronic lymphocytic leukemia (CLL), low-grade non-Hodgkin lymphoma (NHL)

(recurrent or persistent) fludarabine refractory or with less than 6 months duration of complete response (CR) between courses of conventional therapy

- Multiple myeloma, progressive disease after autologous stem cell transplant or

as planned tandem (allogeneic transplant after prior autologous stem cell transplant)

- Waldenstroms macroglobulinemia (failed one standard regimen)

- High grade NHL and diffuse large B-cell lymphoma (DLBCL)

- Not eligible for conventional myeloablative HSCT OR failed autologous HSCT

- First remission lymphoblastic lymphoma, or small, non-cleaved cell lymphoma or

mantle cell lymphoma

- Hodgkin disease:

- Relapsed or refractory after front-line therapy

- Failed or were not eligible for autologous transplantation

- Failed prior autotransplant

- Age >= 3 and =< 75 years for blood and bone marrow transplants and age >= 3, < 60 for

cord blood transplants

- No serious uncontrolled psychiatric illness

- No concomitant active malignancy other than non-melanoma skin cancer

- Non-pregnant and non-nursing women (women or men with reproductive potential should

agree to use an effective means of birth control)

- Patients may have received prior autologous bone marrow transplant (BMT) or prior

myeloablative allogeneic BMT (at least 60 days have elapsed)

- At least 2 weeks since prior chemotherapy, radiation treatment and/or surgery

- Informed consent

- DONOR: Permissible HLA matching: Related donors- single antigen mismatch at HLA A, B

or DRB 1; unrelated donors- a single antigen mismatch at HLA A, B, or C, +/- additional single allele level mismatch at A, B, C or DRB1; cord blood >= 4 out of 6 antigen match at HLA A, B, DRB1)

- DONOR: Compatibility at the four most informative HLA loci: A, B, C and DRB1 are

important for reducing the risk of GVHD and successful transplant outcomes; the A, B, C and DRB1 loci comprise 8 possible alleles (a haplotype being inherited from each parent); one additional locus, HLA-DQ, is also typed to ascertain haplotypes and assist in the search for a compatible donor; however mismatching at DQ has not been shown to be associated with adverse outcomes; high resolution molecular typing (at the allele level) is now the standard of care for unrelated donor searches and allows greater refinement of the search strategy

- DONOR: Matched related donor: a single antigen mismatch at A, B, or the DR transplant

from a family member is associated with a higher risk of GVHD but similar overall survival when compared to full identity at these 3 regions; related donor/recipient pairs must be matched at 5 of 6 HLA antigens (A, B, DRBl)

- DONOR: Unrelated donor: when evaluating patients for unrelated donor transplant, a

higher degree of matching is preferred due to minimize the risk of GVHD; the A, B, C, DRB1 and DQ loci, comprising 10 possible alleles, will be typed routinely for all unrelated transplants; given the higher risk of TRM in mismatched transplants, RIT is often the best way to mitigate the risk; evolving data from the National Marrow Donor Program now makes it possible to estimate the risks of donor-recipient HLA mismatch at the allele or antigen level; the higher risk from HLA-mismatching must be carefully assessed with respect to the clinical urgency and the patient's risk by the transplant physician; antigen level mismatches at DQ are inconsequential to transplant outcomes and are ignored with respect to donor selection for the purposes of this protocol, with matching requirements confined to the 8 loci involving HLA A, B, C and DRB1; for the purpose of this protocol, a single antigen mismatch at HLA A, B, or C, with or without additional single allele level mismatch may participate in this protocol for voluntary unrelated donors (blood or marrow); patients must be at least antigen-level matched at DRB1

- DONOR: If a patient has no suitable family donor matched for 5 of 6 HLA antigens (A,

B, DRB1) and no suitable unrelated donor is identified or for reasons of urgency, the patient can be considered a candidate for cord blood transplant, provided a cord blood donor is identified with a >= 4 out of 6 antigen match at HLA A, B, DRB1 antigens; the cord blood product must provide a minimum of 2 x 10^7 nucleated cells/kg, test negative for HIV and Hepatitis A, Band C, and sterility assays have no growth; the cord blood products are located through the National Marrow Donor Program, the American Registry, or the Bone Marrow Donor Worldwide or other established registries, and may be stored in the N. Y Placental Cord Blood Bank, the St. Louis Cord Blood Bank, or any of the established, registered International blood and marrow banks

- DONOR: Donor must be healthy and have nonreactive test results for all infectious

disease assays as required by state and federal regulations; donors who screen seropositive for hepatitis and/or syphilis must be cleared by infectious disease consultation

- DONOR: The donor must have no uncontrolled cardiopulmonary, renal, endocrine, hepatic

or psychiatric disease to render donation unsafe

- DONOR: The donor must be able to give informed consent for peripheral blood stem cell

collection or bone marrow collection

- DONOR: Syngeneic donors are not eligible

- DONOR: Donors who have poor peripheral venous access, may require central venous line

placement for stem cell apheresis Exclusion Criteria:

- Uncontrolled central nervous system (CNS) disease (for hematologic malignancies)

- Karnofsky (adult) or Lansky (for =< 16 years) performance status =< 50%

- Diffusing capacity of the lung for carbon monoxide (DLCO) less than 40% predicted,

corrected for hemoglobin (Hb) and/or alveolar ventilation

- Cardiac: left ventricular ejection fraction less than 40%

- Bilirubin >= 3 x upper limit of normal

- Liver alkaline phosphatase >= 3 x upper limit of normal

- Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvate

transaminase (SGPT) >= 3 x upper limit of normal

- Child's class B and C liver failure

- Calculated creatinine clearance < 40 cc/min by the modified Cockcroft-Gault formula

for adults or the Schwartz formula for pediatrics

- Patients who have received maximally allowed doses (given in 2 Gy fractions, or

equivalent) of previous radiation therapy to various organs as follows:

- Mediastinum 40 Gy

- Heart (any volume) 36 Gy

- Whole lungs 12 Gy

- Small bowel (any volume) 46 Gy

- Kidneys 12 Gy

- Whole liver 20 Gy

- Spinal cord (any volume) 36 Gy

- Whole brain 30 Gy Enrollment of patients who previously receive higher than

allowed dose of radiation to a small volume of lungs, liver, and brain will be determine by the discretion of the radiation oncologist on the study

- Uncontrolled diabetes mellitus, cardiovascular disease, active serious infection or

other condition which, in the opinion of treating physician, would make this protocol unreasonably hazardous for the patient

- Human immunodeficiency virus (HIV) positive

- Patients who in the opinion of the treating physician are unlikely to comply with the

restrictions of allogeneic stem cell transplantation based on formal psychosocial screening

- Females of childbearing potential with a positive pregnancy test

Locations and Contacts

Roswell Park Cancer Institute, Buffalo, New York 14263, United States
Additional Information

Starting date: January 2009
Last updated: September 16, 2013

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017