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

NCT01027000 | Completed Phase 2 Results DMC

• 4 other identifiers: CALGB 100701CDR0000660555U10CA031946NCI-2011-01995
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 25

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.

Conditions

Leukemia; Lymphoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 2-year Progression-free Survival in Early Disease Participants

  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).

  2 years post-registration

Secondary Outcomes (6)

• Response

  5 years post-registration

• Acute Graft-vs-host Disease (GVHD)

  5 years post-registration

• Chronic GVHD

  5 years post-registration

• Treatment-related Mortality

  6 months post-transplant

• Overall Survival

  5 years post-registration

Study Arms (1)

Treatment (Combination of chemotherapy and transplant)

EXPERIMENTAL

See detailed description

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

Interventions

rituximab BIOLOGICAL

Treatment (Combination of chemotherapy and transplant)

busulfan DRUG

Treatment (Combination of chemotherapy and transplant)

cyclophosphamide DRUG

Treatment (Combination of chemotherapy and transplant)

fludarabine phosphate DRUG

Treatment (Combination of chemotherapy and transplant)

methotrexate DRUG

Treatment (Combination of chemotherapy and transplant)

sirolimus DRUG

Treatment (Combination of chemotherapy and transplant)

tacrolimus DRUG

Treatment (Combination of chemotherapy and transplant)

allogeneic stem cell transplant PROCEDURE

Treatment (Combination of chemotherapy and transplant)

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator
• Genentech, Inc.: collaborator
• Biologics, Inc.: collaborator

Study Sites (25)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010-3000, United States

Location

Tunnell Cancer Center at Beebe Medical Center

Lewes, Delaware, 19958, United States

Location

CCOP - Christiana Care Health Services

Newark, Delaware, 19713, United States

Location

Florida Hospital Cancer Institute at Florida Hospital Orlando

Orlando, Florida, 32803-1273, United States

Location

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

Tampa, Florida, 33612-9497, United States

Location

University of Chicago Cancer Research Center

Chicago, Illinois, 60637-1470, United States

Location

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, 52242-1002, United States

Location

Union Hospital of Cecil County

Elkton, Maryland, 21921, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber/Brigham and Women's Cancer Center

Boston, Massachusetts, 02115, United States

Location

Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, 63110, United States

Location

UNMC Eppley Cancer Center at the University of Nebraska Medical Center

Omaha, Nebraska, 68198-6805, United States

Location

Cancer Institute of New Jersey at Cooper - Voorhees

Voorhees Township, New Jersey, 08043, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

Monter Cancer Center of the North Shore-LIJ Health System

Lake Success, New York, 11042, United States

Location

CCOP - North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Don Monti Comprehensive Cancer Center at North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Long Island Jewish Medical Center

New Hyde Park, New York, 11040, United States

Location

New York Weill Cornell Cancer Center at Cornell University

New York, New York, 10021, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157-1096, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210-1240, United States

Location

Oklahoma University Cancer Institute

Oklahoma City, Oklahoma, 73104, United States

Location

MeSH Terms

Conditions

Leukemia; Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Rituximab; Busulfan; Cyclophosphamide; fludarabine phosphate; Methotrexate; Sirolimus; Tacrolimus

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Macrolides; Lactones

Results Point of Contact

• Title: Edwin P. Alyea, MD
• Organization: Dana Farber Cancer Institute

edwin_alyea@dfci.harvard.edu

Study Officials

• Edwin P. Alyea, MD

  Dana-Farber Cancer Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2009
• First Posted: December 7, 2009
• Study Start: February 1, 2010
• Primary Completion: January 1, 2016
• Study Completion: April 1, 2023
• Last Updated: May 6, 2023
• Results First Posted: May 3, 2017

Record last verified: 2023-04

Locations

US (25)