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Trial record 1 of 1 for:    NCT01027000
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Donor Stem Cell Transplant in Treating Patients With High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01027000
Recruitment Status : Active, not recruiting
First Posted : December 7, 2009
Results First Posted : May 3, 2017
Last Update Posted : June 12, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:

RATIONALE: Giving low doses of chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. Also, monoclonal antibodies, such as rituximab, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal 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, sirolimus, and methotrexate after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well donor stem cell transplant works in treating patients with high-risk chronic lymphocytic leukemia or small lymphocytic lymphoma.

Condition or disease Intervention/treatment Phase
Leukemia Lymphoma Biological: rituximab Drug: busulfan Drug: cyclophosphamide Drug: fludarabine phosphate Drug: methotrexate Drug: sirolimus Drug: tacrolimus Procedure: allogeneic stem cell transplant Phase 2

  Show Detailed Description

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 68 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Reduced-Intensity Allogeneic Stem Cell Transplant for High-Risk Chronic Lymphocytic Leukemia (CLL)
Study Start Date : February 2010
Primary Completion Date : January 2016

Arms and Interventions

Arm Intervention/treatment
Experimental: Treatment (Combination of chemotherapy and transplant)
See detailed description
Biological: rituximab Drug: busulfan Drug: cyclophosphamide Drug: fludarabine phosphate Drug: methotrexate Drug: sirolimus Drug: tacrolimus Procedure: allogeneic stem cell transplant

Outcome Measures

Primary Outcome Measures :
  1. 2-year Progression-free Survival in Early Disease Participants [ Time Frame: 2 years post-registration ]

    Percentage of participants who were alive and progression free at 2 years for participants with early disease stage. The 2 year progression free survival, with 95% confidence interval, was estimated using the Kaplan Meier method.

    A progression is defined as one of the following events:

    • >= 50% increase in the products of at least two lymph nodes on two consecutive determinations two weeks apart (at least one lymph node must be >= 2 cm); appearance of new palpable lymph nodes.
    • >= 50% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margin; appearance of palpable hepatomegaly or splenomegaly, which was not previously present.
    • > 50% increase in peripheral blood lymphocytes with an absolute increase > 5000/μL.
    • Transformation to a more aggressive histology (i.e., Richter's syndrome or prolymphocytic leukemia with >= 56% prolymphocytes).

Secondary Outcome Measures :
  1. Response [ Time Frame: 5 years post-registration ]
  2. Acute Graft-vs-host Disease (GVHD) [ Time Frame: 5 years post-registration ]
  3. Chronic GVHD [ Time Frame: 5 years post-registration ]
  4. Treatment-related Mortality [ Time Frame: 6 months post-transplant ]
  5. Overall Survival [ Time Frame: 5 years post-registration ]
  6. Chimerism for CD3 [ Time Frame: 5 years post-registration ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 69 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Patient Eligibility:

  1. Diagnosis of B-cell chronic lymphocytic leukemia or B-cell small lymphocytic lymphoma.

    Diagnosis should be according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Criteria

    1. Early Disease Cohort - Patients in the early disease cohort must include one or more of the following:

      • FISH showing deletion 17p in ≥ 20% of cells (either at diagnosis or any time prior to study entry) either alone or in combination with other cytogenetic abnormalities
      • FISH showing del 11q in ≥ 20% of cells (either at diagnosis or any time prior to study entry) either alone or in combination with other cytogenetic abnormalities, unless the patient has achieved a complete remission by IWCLL 2008 which includes CT scan, bone marrow morphology and flow cytometry
      • Failure to achieve a partial response with initial chemotherapy, but with lack of progression. These patients may receive a second therapy to improve their response prior to transplant.
      • Patients who, at the time of first progression, have a 17p deletion by FISH in ≥ 20% of cells, either alone or in combination with other cytogenetic abnormalities.

      The duration of the first progression is not specified.

      • In addition, patients in the early disease cohort must have all of the following:

        • Received at least 2 cycles of induction therapy. It is expected that most patients will receive at least 4 months of therapy prior to enrollment, but this is not required. Suggested regimens include but are not limited to the following: fludarabine plus rituximab, fludarabine, cyclophosphamide plus rituximab, pentostatin, cyclophosphamide plus rituximab, bendumustine plus rituximab, or alemtuzumab alone or in combination with other agents. Patients may receive no more than 2 different regimens prior to proceeding to transplantation.
        • Nodes ≤ 5 cm
    2. Advanced Disease Cohort - Patients in the advanced disease cohort must include one or more of the following:

      • FISH showing deletion 17p in ≥ 20% of cells (regardless of interval from initial therapy) either alone or in combination with other cytogenetic abnormalities
      • First progression < 24 months after completing therapy. This includes progression on initial therapy.
      • Second or subsequent progression
      • In addition, patients in the advanced disease cohort must have all of the following:

        • Stable disease or better by the Revised IWCLL 2008 NCI Criteria to their most recent chemotherapy
        • Nodes ≤ 5 cm
  2. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
  3. Age Requirement - Patients must be between ≥ 18 and < 70 years of age
  4. Cytotoxic Chemotherapy or Alemtuzamab - There must be at least 4 weeks after day 1 of the last cycle of cytotoxic chemotherapy, or alemtuzamab.
  5. Human Immunodeficiency Virus (HIV) Status - Patients must have no HIV infection.

    Allogeneic transplantation in the HIV patient population is not well-defined and there are likely to be requirements for concomitant anti-HIV therapy and anti-GVHD therapy that would create potentially dangerous pharmacokinetic interactions among the different agents that could constrain therapeutic options for controlling both HIV and GVHD.

  6. Hepatitis B and C - Patients must have no Hepatitis B sAg, anti-HBc or HCV.
  7. Diffusion capacity of carbon monoxide DLCO must be ≥ 40% predicted
  8. Left ventricular ejection fraction (LVEF) by Echocardiogram (ECHO) or Multiple gated acquisition (MUGA) must be ≥ 30%
  9. Diabetes or Serious Infection - Patients must have no uncontrolled diabetes mellitus or active uncontrolled serious infections
  10. Pregnancy and Nursing Status - Patients must be non-pregnant and non-nursing. Treatment under this protocol would expose a fetus to significant risks. Women of childbearing potential should have a negative pregnancy test prior to study entry.

    Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Appropriate methods of birth control include oral contraceptives, implantable hormonal contraceptives (Norplant®), or double barrier method (diaphragm plus condom).

  11. Richter's Transformation - Patients must have no history of Richter's transformation.
  12. Initial Required Laboratory Values:

    • Serum Creatinine < 2 mg/dL
    • Calculated Creatinine Clearance ≥ 40 mL/min
    • AST < 3 x ULN
    • Total Bilirubin < 2 mg/dL (except for Gilbert's syndrome)

Donor Eligibility:

  1. Donors may be either a 6/6 HLA-matched related donor by low-resolution typing at HLA A, B, DR.
  2. Donors may be an 8/8 HLA-matched unrelated donor at HLA A, B, C, DR. Unrelated donors will be analyzed by molecular typing at both HLA Class I and Class II (A, B, C, DR loci).
  3. Syngeneic donors are not eligible
  4. Donors must be healthy and must be an acceptable donor as per institutional standards for stem cell donation.
  5. There will be no donor age restriction.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01027000

  Show 25 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Genentech, Inc.
Biologics, Inc.
Study Chair: Edwin P. Alyea, MD Dana-Farber Cancer Institute
More Information

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT01027000     History of Changes
Other Study ID Numbers: CALGB 100701
CDR0000660555 ( Registry Identifier: Physician Data Query )
U10CA031946 ( U.S. NIH Grant/Contract )
NCI-2011-01995 ( Registry Identifier: NCI Clinical Trials Reporting Office )
First Posted: December 7, 2009    Key Record Dates
Results First Posted: May 3, 2017
Last Update Posted: June 12, 2017
Last Verified: May 2017

Keywords provided by Alliance for Clinical Trials in Oncology:
refractory chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia
contiguous stage II small lymphocytic lymphoma
noncontiguous stage II small lymphocytic lymphoma
recurrent small lymphocytic lymphoma
stage I small lymphocytic lymphoma
stage III small lymphocytic lymphoma
stage IV small lymphocytic lymphoma

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Fludarabine phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Abortifacient Agents, Nonsteroidal
Abortifacient Agents