Umbilical Cord Blood (UCB) Transplant, Fludarabine, Melphalan, and Anti-thymocyte Globulin (ATG) in Treating Patients With Hematologic Cancer

Lymphoma Clinical Trial

Official title:

Transplantation of Two Partially Matched Umbilical Cord Blood Units Following Reduced Intensity Conditioning to Enhance Engraftment and Limit Transplant-Related Mortality in Adults With Hematologic Malignancies

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00827099
• Other study ID #: CDR0000632453
• Secondary ID: BMTGG-NSH-801
• Status: Terminated
• Phase: Phase 2
• First received: January 21, 2009
• Last updated: March 19, 2012
• Start date: June 2006
• Est. completion date: November 2009

Study information

• Verified date: March 2012
• Source: Northside Hospital, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Giving low doses of chemotherapy before a donor umbilical cord blood transplant helps stop the growth of cancer 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 cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and mycophenolate mofetil after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving umbilical cord blood transplant together with fludarabine, melphalan, and antithymocyte globulin works in treating patients with hematologic cancer.

Description:

OBJECTIVES:

Primary

• To evaluate the 100-day transplant-related (non-relapse) mortality in patients with hematologic malignancies undergoing reduced-intensity conditioning comprising fludarabine phosphate, melphalan, and anti-thymocyte globulin followed by sequential umbilical cord blood transplantation (UCBT) from 2 partially-matched unrelated donors.

Secondary

• To evaluate the 12-month transplant-related (non-relapse) mortality.

• To evaluate the days to neutrophil engraftment (ANC > 500/mm³).

• To evaluate the days to platelet engraftment (platelet count > 20,000/mm³ [unsupported]).

• To evaluate the risk of acute and chronic graft-vs-host disease.

• To evaluate percent donor chimerism contribution of each cord unit.

• To evaluate relapse rate.

• To evaluate disease-free and overall survival.

• To evaluate transfusion support needed for UCBT recipients.

OUTLINE:

• Conditioning regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3, melphalan IV over 30-60 minutes on day -2, and anti-thymocyte globulin IV over 4-6 hours on days -4 to -2.

• Transplantation: Patients undergo two sequential umbilical cord blood transplantations on day 0.

• Graft-vs-host disease (GVHD) prophylaxis: Patients receive tacrolimus IV continuously and then orally twice daily beginning on day -1 and continuing until day 60, followed by a taper until day 180 in the absence of GVHD. Patients also receive mycophenolate mofetil IV or orally twice daily beginning on day 0 and continuing until day 30, followed by a taper until day 60 in the absence of GVHD.

After completion of study treatment, patients are followed periodically.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: November 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of hematologic malignancy for which a reduced-intensity allogeneic stem cell transplantation is deemed clinically appropriate, including any of the following:

• Chronic myelogenous leukemia, meeting one of the following criteria:

• In first chronic phase AND failed imatinib mesylate therapy, defined as failure to obtain a hematologic remission by 3 months or major cytogenetic response (Ph+ cells < 35%) by 12 months, or demonstrated clonal evolution or disease progression while on therapy

• In accelerated phase with < 15% blasts

• In blast crisis that has entered into a second chronic phase following induction chemotherapy

• Acute myelogenous leukemia, meeting one of the following criteria:

• In second or subsequent completion remission*

• Failed primary induction chemotherapy, but subsequently entered into a complete remission* with = 2 subsequent re-induction chemotherapy treatment(s)

• In first complete remission* with poor-risk cytogenetics NOTE: *Complete remission is defined as < 5% blasts in bone marrow, no definitive evidence of disease by morphology, flow cytometry, or genetic studies, and no circulating blasts. Neutrophil and platelet count recovery will not be required.

• Acute lymphoblastic leukemia, meeting one of the following criteria:

• In second or subsequent complete remission

• In first complete remission AND t(9;22)

• Myelodysplastic syndromes, meeting the following criteria:

• High-risk disease, defined as International Prognostic Scoring System score of = 1.5

• Less than 10% blasts at the time of study enrollment

• Chronic myelomonocytic leukemia

• Less than 10% blasts at the time of study enrollment

• Myeloid metaplasia with myelofibrosis with poor-risk features, meeting one of the following criteria:

• Age < 55 years AND a Lille score of 1

• Lille score of 2

• Hemoglobin < 10 g/dL AND abnormal karyotype

• Chronic lymphocytic leukemia/prolymphocytic leukemia, meeting all of the following criteria:

• Rai stage I-IV disease

• Failed = 1 prior chemotherapy regimen, including fludarabine, or autologous stem cell transplantation

• Chemosensitive or stable, non-bulky disease prior to transplant

• Received = 3 prior chemotherapy regimens (monoclonal antibody therapy and involved-field radiotherapy are not considered prior regimens)

• Low-grade B-cell non-Hodgkin lymphoma (NHL) (small lymphocytic lymphoma, follicular center [grade 1 or 2] lymphoma, or marginal zone lymphoma), meeting all of the following criteria:

• Failed = 1 prior chemotherapy regimen or autologous stem cell transplantation

• Chemosensitive or stable, non-bulky disease prior to transplant

• Received = 3 prior chemotherapy regimens (monoclonal antibody therapy and involved-field radiotherapy are not considered prior regimens)

• Intermediate-grade B-cell or T-cell NHL or mantle cell NHL, meeting all of the following criteria:

• Failed to achieve remission or recurred after either conventional chemotherapy or autologous stem cell transplantation

• Chemosensitive, non-bulky disease prior to transplant

• Hodgkin lymphoma, meeting all of the following criteria:

• Relapsed after prior autologous stem cell transplantation or after = 2 combination chemotherapy regimens AND ineligible for autologous peripheral blood stem cell transplantation

• Chemosensitive, non-bulky disease prior to transplant

• Multiple myeloma, meeting one of the following criteria:

• Relapsed after autologous stem cell transplantation

• Relapsed after conventional therapies AND not a candidate for autologous stem cell transplantation

• No HLA-matched related or unrelated donor available

• Has two umbilical cord blood units available that are matched at = 4/6 HLA A, B, and DRB1 with the patient and with each other (HLA C and DQ will not be used in the match strategy)

• Total combined nucleated cell dose from the 2 umbilical cord blood units must be > 3.7 x 10^7 nucleated cells/kg (pre-freeze dose) 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:

• Karnofsky performance status 80-100%

• Adapted, weighted Charlson Comorbidity Index < 3

• Serum creatinine = 2.0 mg/dL

• AST or ALT < 3 times upper limit of normal (ULN)

• Bilirubin < 1.5 times ULN

• Not pregnant or nursing

• LVEF = 40%

• DLCO > 50%

• No hypoxia at rest with oxygen saturation < 92% on room air (corrected with bronchodilator therapy)

• No active opportunistic infection (e.g., fungal pneumonia, tuberculosis, or viral infection)

• No active hepatitis B or C infection that, in the opinion of a gastroenterologist or the transplant committee, places the patient at moderate- to high-risk for developing severe hepatic disease

• No HIV infection

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Lymphoma
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Myeloproliferative Disorders
• Neoplasms, Plasma Cell
• Plasmacytoma
• Preleukemia

Intervention

Biological:
• anti-thymocyte globulin
anti-thymocyte globulin

Drug:
• fludarabine phosphate
fludarabine phosphate
• Melphalan
melphalan
• mycophenolate mofetil
mycophenolate mofetil
• tacrolimus
tacrolimus

Procedure:
• umbilical cord blood transplantation
umbilical cord blood transplantation

Locations

Country	Name	City	State
United States	Blood and Marrow Transplant Group of Georgia	Atlanta	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Northside Hospital, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With 100 Day Transplant-related Mortality (TRM)	100 Day TRM is death within 100 days from transplant related complications	100 days	Yes
Secondary	Number of Patients That Engrafted Blood Counts by 30 Days After Transplant	Number of patients whose Absolute Neutrophil Count (ANC) recovered to >500 x10^3/uL for at least 3 consecutive days after transplant	Day 30	Yes
Secondary	Percentage of Donor and Host Chimerism of Each Cord Blood Unit	Evaluate the percentages of donor and host chimerism at multiple times post-transplant including Day 30, Day 60, Day 90 and monthly thereafter if the patient is not considered to have full chimerism.	day 30, day 60, day 90	Yes
Secondary	Number of Patients Who Experience Acute and Chronic Graft-vs-host Disease After Transplant.	Patients will be evaluated regularly for the development of graft versus host disease both acute & chronic.	Day 30	Yes
Secondary	Number of Patients Who Experience Disease Relapse Post-transplant	Patients will have routine restaging to assess disease response at Day 100, 6 months, 1 year, 18 months and 24 months. If disease relapse is suspected, the patient will be evaluated at that time.	Day 100, 6 months, 1 year, 18 months, 24 months	No
Secondary	Number of Patients Who Survive Following Treatment on This Protocol	Patients will be followed until death	Through Death	No