Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00060424
Other study ID # 1711.00
Secondary ID NCI-2010-01276NC
Status Completed
Phase Phase 2
First received May 6, 2003
Last updated December 5, 2017
Start date March 2003
Est. completion date September 22, 2010

Study information

Verified date December 2017
Source Fred Hutchinson Cancer Research Center
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This clinical trial studies how well giving fludarabine phosphate together with total-body irradiation (TBI) before donor peripheral blood stem cell transplant works in treating patients with chronic lymphocytic leukemia or small lymphocytic leukemia. Giving low doses of chemotherapy, such as fludarabine phosphate, and TBI before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. Giving chemotherapy before or after peripheral blood stem cell transplant also stops 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 cyclosporine and mycophenolate mofetil before and after the transplant may stop this from happening.


Description:

PRIMARY OBJECTIVES:

I. To determine whether nonmyeloablative allogeneic hematopoietic stem cell transplantation (HSCT) from matched-related donors can improve the probability of survival 18 months after treatment for fludarabine (fludarabine phosphate)-refractory, fludarabine phosphate, cyclophosphamide, and rituximab (FCR)-failed, or del 17p chronic lymphocytic leukemia (CLL) beyond that observed in historical controls (30%).

SECONDARY OBJECTIVES:

I. To assess the rate of relapse with allogeneic HSCT using nonmyeloablative conditioning for patients with fludarabine-refractory, FCR-failed, or del 17p CLL compared with historical data on autologous HSCT.

II. To estimate the incidence of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD in patients with CLL treated with low-dose TBI, fludarabine, peripheral blood stem cell (PBSC) infusion and immunosuppression with cyclosporine and mycophenolate mofetil.

III. To characterize the rate and types of infections with this regimen.

IV. To estimate the rate of transplant-related mortality in the first 200 days.

OUTLINE:

NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 and TBI on day 0.

TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0.

GVHD PROPHYLAXIS: Patients receive cyclosporine orally (PO) every 12 hours on days -3 to 180 with taper beginning on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27.

After completion of study treatment, patients are followed up at 12 and 18 months and then annually for 5 years.


Recruitment information / eligibility

Status Completed
Enrollment 21
Est. completion date September 22, 2010
Est. primary completion date September 2010
Accepts healthy volunteers No
Gender All
Age group 21 Years and older
Eligibility Inclusion Criteria:

- Patients with CLL (or small lymphocytic lymphoma) or diagnosis of CLL that progresses to prolymphocytic leukemia (PLL), or T-cell CLL or PLL

- Patients with B-Cell CLL or PLL who have at least one of the following:

- Failed to meet National Cancer Institute (NCI) Working Group criteria for complete or partial response after therapy with a regimen containing fludarabine (or another nucleoside analog, e.g. cladribine [2-CDA], pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing fludarabine (or another nucleoside analog)

- Failed FCR combination chemotherapy at any time point

- Had de novo of acquired "17p deletion" cytogenetic abnormality; patients should have received induction chemotherapy but could be transplanted in first (1st) complete response (CR)

- Patient has a suitable human leukocyte antigen (HLA)-matched related donor who is willing to undergo leukapheresis initially for collection of PBSC and subsequently for collection of peripheral blood mononuclear cells (PBMC) with filgrastim (G-CSF) mobilization and willing to donate stem cells

- DONOR: Related donor who is HLA phenotypically or genotypically identical at the allele level at HLA-A, -B, -C, -DRB1, and -DQB1

- DONOR: Donor must consent to G-CSF administration and leukapheresis

- DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian)

Exclusion Criteria:

- Infection with human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV)-1, or HTLV-2

- Active central nervous system (CNS) involvement with CLL

- Patients with active non-hematologic malignancies (except non-melanoma skin cancers)

- Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence

- Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment

- Pregnant or breastfeeding women

- Karnofsky score =< 70

- Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month

- Cytotoxic agents for "cytoreduction" (with the exception of imatinib mesylate [Gleevec], cytokine therapy, hydroxyurea, chlorambucil or Rituxan) within three weeks of the initiation of conditioning

- Active bacterial or fungal infections unresponsive to medical therapy

- Cardiovascular: cardiac ejection fraction < 40%; patients with poorly controlled hypertension despite multiple antihypertensives

- Pulmonary: diffusing capacity of carbon monoxide (DLCO) < 40%, total lung capacity (TLC) < 40%, forced expiratory volume in one second (FEV1) < 40% and/or requiring continuous supplementary oxygen, or severe deficits in pulmonary function testing as defined by pulmonary consultant service

- Liver function abnormalities: patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dL, or symptomatic biliary disease

- DONOR: Age < 12 years

- DONOR: Identical twin

- DONOR: Pregnancy

- DONOR: Infection with HIV

- DONOR: Inability to achieve adequate venous access

- DONOR: Known allergy to filgrastim (G-CSF)

- DONOR: Current serious systemic illness

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Cyclosporine
Given PO
Fludarabine Phosphate
Given IV
Procedure:
Hematopoietic Cell Transplantation
Undergo allogeneic peripheral blood stem cell transplant
Other:
Laboratory Biomarker Analysis
Correlative studies
Drug:
Mycophenolate Mofetil
Given PO
Procedure:
Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic peripheral blood stem cell transplant
Radiation:
Total-Body Irradiation
Undergo TBI

Locations

Country Name City State
Italy University of Torino Torino
United States Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle Washington
United States Veterans Administration Center-Seattle Seattle Washington

Sponsors (2)

Lead Sponsor Collaborator
Fred Hutchinson Cancer Research Center National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Italy, 

Outcome

Type Measure Description Time frame Safety issue
Primary Overall Survival Number of patients surviving 18 months post-transplant. At 18 months
Secondary Rate of Relapse Number of patients with relapsed disease post-transplant. Relapse/progression is defined as 1) Physical exam/Imaging studies (nodes, liver, and/or spleen) =50% increase or new, 2) circulating lymphocytes by morphology and/or flow cytometry =50% increase, or 3) lymph node Biopsy Richter's transformation. 18 months
Secondary Acute Grade II-IV GVHD and Chronic (Extensive) GVHD Number of patients who developed acute/chronic GVHD post-transplant. aGVHD Stages
Skin:
a maculopapular eruption involving < 25% BSA a maculopapular eruption involving 25 - 50% BSA generalized erythroderma generalized erythroderma with bullous formation and often with desquamation
Liver:
bilirubin 2.0 - 3.0 mg/100 mL bilirubin 3 - 5.9 mg/100 mL bilirubin 6 - 14.9 mg/100 mL bilirubin > 15 mg/100 mL
Gut:
Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall.
aGVHD Grades Grade II: Stage 1 - 3 skin and/or stage 1 gut involvement and/or stage 1 liver involvement Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death
aGVHD: 100 days after transplant; cGVHD: 1 Year after transplant.
Secondary Rate and Types of Infections Number of infections patients experienced, by infection type. 18 months
Secondary Transplant-related Mortality Defined as death before day +200 not related to progression of disease. At 200 days
See also
  Status Clinical Trial Phase
Recruiting NCT05400122 - Natural Killer (NK) Cells in Combination With Interleukin-2 (IL-2) and Transforming Growth Factor Beta (TGFbeta) Receptor I Inhibitor Vactosertib in Cancer Phase 1
Enrolling by invitation NCT01804686 - A Long-term Extension Study of PCI-32765 (Ibrutinib) Phase 3
Completed NCT02057185 - Occupational Status and Hematological Disease
Active, not recruiting NCT04240704 - Safety and Preliminary Efficacy of JBH492 Monotherapy in Patients With CLL and NHL Phase 1
Recruiting NCT03676504 - Treatment of Patients With Relapsed or Refractory CD19+ Lymphoid Disease With T Cells Expressing a Third-generation CAR Phase 1/Phase 2
Active, not recruiting NCT03280160 - Protocol GELLC-7: Ibrutinib Followed by Ibrutinib Consolidation in Combination With Ofatumumab Phase 2
Active, not recruiting NCT03844048 - An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial Phase 3
Completed NCT00038025 - A Study Of Deoxycoformycin(DCF)/Pentostatin In Lymphoid Malignancies Phase 2
Recruiting NCT04904588 - HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide Phase 2
Terminated NCT02231853 - Phase I/II Trial of Early Infusion of Rapidly-generated Multivirus Specific T Cells (MVST) to Prevent Post Transplant Viral Infections Phase 1
Recruiting NCT05417165 - Anti-pneumococcal Vaccine Strategy in Patients With Chronic Lymphocytic Leukemia Phase 2
Recruiting NCT04028531 - Understanding Chronic Lymphocytic Leukemia
Completed NCT00001637 - Immunosuppressive Preparation Followed by Blood Cell Transplant for the Treatment of Blood Cancers in Older Adults Phase 2
Completed NCT02910583 - Ibrutinib Plus Venetoclax in Subjects With Treatment-naive Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma (CLL/SLL) Phase 2
Completed NCT01527045 - Donor Atorvastatin Treatment in Preventing Severe Acute GVHD After Nonmyeloablative Peripheral Blood Stem Cell Transplant in Patients With Hematological Malignancies Phase 2
Recruiting NCT04679012 - Polatuzumab Vedotin in Combination With Chemotherapy in Subjects With Richter's Transformation Phase 2
Recruiting NCT05405309 - RP-3500 and Olaparib in DNA Damage Repair Pathway Deficient Relapsed/Refractory Chronic Lymphocytic Leukemia Phase 1/Phase 2
Active, not recruiting NCT05023980 - A Study of Pirtobrutinib (LOXO-305) Versus Bendamustine Plus Rituximab (BR) in Untreated Patients With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) Phase 3
Recruiting NCT04553692 - Phase 1a/1b Study of Aplitabart (IGM-8444) Alone or in Combination in Participants With Relapsed, Refractory, or Newly Diagnosed Cancers Phase 1
Completed NCT04666025 - SARS-CoV-2 Donor-Recipient Immunity Transfer