Donor Stem Cell Transplant in Treating Patients With High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

This study is ongoing, but not recruiting participants.
Genentech, Inc.
Biologics, Inc.
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology Identifier:
First received: December 4, 2009
Last updated: July 31, 2015
Last verified: July 2015

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 Intervention Phase
Biological: rituximab
Drug: busulfan
Drug: cyclophosphamide
Drug: fludarabine phosphate
Drug: methotrexate
Drug: sirolimus
Drug: tacrolimus
Procedure: allogeneic stem cell transplant
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Reduced-Intensity Allogeneic Stem Cell Transplant for High-Risk Chronic Lymphocytic Leukemia (CLL)

Resource links provided by NLM:

Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • 2-year progression-free survival [ Time Frame: 2 years post-registration ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response [ Time Frame: 5 years post-registration ] [ Designated as safety issue: No ]
  • Acute graft-vs-host disease (GVHD) [ Time Frame: 5 years post-registration ] [ Designated as safety issue: No ]
  • Chronic GVHD [ Time Frame: 5 years post-registration ] [ Designated as safety issue: No ]
  • Treatment-related mortality [ Time Frame: 6 months post-transplant ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 5 years post-registration ] [ Designated as safety issue: No ]
  • Chimerism for CD3 [ Time Frame: 5 years post-registration ] [ Designated as safety issue: No ]

Enrollment: 78
Study Start Date: February 2010
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Show Detailed Description


Ages Eligible for Study:   18 Years to 69 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01027000

  Hide Study Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
United States, Delaware
Tunnell Cancer Center at Beebe Medical Center
Lewes, Delaware, United States, 19958
CCOP - Christiana Care Health Services
Newark, Delaware, United States, 19713
United States, Florida
Florida Hospital Cancer Institute at Florida Hospital Orlando
Orlando, Florida, United States, 32803-1273
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
Tampa, Florida, United States, 33612-9497
United States, Illinois
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
United States, Iowa
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, United States, 52242-1002
United States, Maryland
Union Hospital of Cecil County
Elkton MD, Maryland, United States, 21921
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Dana-Farber/Brigham and Women's Cancer Center
Boston, Massachusetts, United States, 02115
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
Saint Louis, Missouri, United States, 63110
United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-6805
United States, New Jersey
Cancer Institute of New Jersey at Cooper - Voorhees
Voorhees, New Jersey, United States, 08043
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Monter Cancer Center of the North Shore-LIJ Health System
Lake Success, New York, United States, 11042
CCOP - North Shore University Hospital
Manhasset, New York, United States, 11030
Don Monti Comprehensive Cancer Center at North Shore University Hospital
Manhasset, New York, United States, 11030
Long Island Jewish Medical Center
New Hyde Park, New York, United States, 11040
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
New York Weill Cornell Cancer Center at Cornell University
New York, New York, United States, 10021
United States, North Carolina
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
United States, Ohio
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210-1240
United States, Oklahoma
Oklahoma University Cancer Institute
Oklahoma City, Oklahoma, United States, 73104
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Genentech, Inc.
Biologics, Inc.
Study Chair: Edwin P. Alyea, MD Dana-Farber Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Alliance for Clinical Trials in Oncology Identifier: NCT01027000     History of Changes
Other Study ID Numbers: CALGB 100701, CDR0000660555, U10CA031946, NCI-2011-01995
Study First Received: December 4, 2009
Last Updated: July 31, 2015
Health Authority: United States: NCI Central Institutional Review Board
United States: Food and Drug Administration

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, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Fludarabine phosphate
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses processed this record on August 26, 2015