Nonmyeloablative Stem Cell Transplantation for Chronic Lymphocytic Leukemia (CLL)

NCT00899431 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2007-0871NCI-2012-01620
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if lenalidomide, when given with a stem cell transplant and chemotherapy (bendamustine, fludarabine, and rituximab), can help to control CLL. The safety of this treatment combination will also be studied.

Conditions

Chronic Lymphocytic Leukemia

Keywords

Nonmyeloablative Stem Cell Transplantation; Chronic Lymphocytic Leukemia; CLL; Immunomanipulation; Fludarabine; Lenalidomide; Rituximab; Thymoglobulin; Stem Cell Transplantation

Outcome Measures

Primary Outcomes (1)

• Immunomanipulation After Non-myeloablative Stem Cell Transplantation for CLL (Chronic Lymphocytic Leukemia).

  To compare the need for immunomanipulation within 18 months after non-myeloablative allogeneic transplantation for CLL between the two combination therapies with or without lenalidomide maintenance. For this purpose, "immunomanipulation" is defined as any one of the following events: 1) Cessation of administering tacrolimus treatment with in the first 6 months after allotransplant due to persistent disease or progression. 2) Boost of donor lymphocytic infusion (DLI) administered anytime between 3 and 18 months after allotransplant.

  Up to 18 months after allotransplant.

Secondary Outcomes (1)

• Percentage of Participants With GVHD (Graft Versus Host Disease)

  Up to 6 months after allotransplant

Study Arms (2)

Group 1: Lenalidomide

ACTIVE COMPARATOR

Chemotherapy, Plus Lenalidomide - Lenalidomide starting dose 5 mg by mouth every other day; increase to 5 mg/d daily in 4-5 weeks for 6 - 12 months. Fludarabine 30 mg/m\^2 intravenously daily on days -5, -4, -3. Rituximab 375 mg/m2 intravenously on day -13, and 1000 mg/m\^2 on days -6, +1 and +8. Thymoglobulin 1.0 mg/kg intravenously over 4 hours (day -2 and -1). On Day 0, donor blood stem cells collected will be transplanted over 30-45 minutes. Bendamustine 130 mg/m2/day by vein daily on day -5, -4, -3 (following Fludarabine). Allopurinol 300 mg by mouth daily beginning at the start of lenalidomide therapy and continuing for 3 months.

Drug: Lenalidomide; Drug: Fludarabine; Drug: Rituximab; Drug: Thymoglobulin; Procedure: Stem Cell Transplantation; Drug: Bendamustine; Drug: Allopurinol

Group 2: No Lenalidomide

ACTIVE COMPARATOR

Chemotherapy Treatment, No Lenalidomide - Fludarabine 30 mg/m\^2 intravenously daily on days -5, -4, -3. Rituximab 375 mg/m2 intravenously on day -13, and 1000 mg/m\^2 on days -6, +1 and +8. Thymoglobulin 1.0 mg/kg intravenously over 4 hours (day -2 and -1). On Day 0, donor blood stem cells collected will be transplanted over 30-45 minutes. Bendamustine 130 mg/m2/day by vein daily on day -5, -4, -3 (following Fludarabine).

Drug: Fludarabine; Drug: Rituximab; Drug: Thymoglobulin; Procedure: Stem Cell Transplantation; Drug: Bendamustine

Interventions

Lenalidomide DRUG

Starting dose 5 mg by mouth every other day; increase to 5 mg/d daily in 4-5 weeks for 6 - 12 months

Also known as: CC-5013, Revlimid

Group 1: Lenalidomide

Fludarabine DRUG

30 mg/m\^2 intravenously daily on days -5, -4, -3.

Also known as: Fludara, Fludarabine Phosphate

Group 1: Lenalidomide; Group 2: No Lenalidomide

Rituximab DRUG

375 mg/m2 intravenously on day -13, and 1000 mg/m\^2 on days -6, +1 and +8.

Also known as: Rituxan

Group 1: Lenalidomide; Group 2: No Lenalidomide

Thymoglobulin DRUG

1.0 mg/kg intravenously over 4 hours (day -2 and -1).

Also known as: ATG, rabbit anti-thymocyte globulin

Group 1: Lenalidomide; Group 2: No Lenalidomide

Stem Cell Transplantation PROCEDURE

On Day 0, donor blood stem cells collected will be transplanted over 30-45 minutes.

Also known as: SCT, Nonmyeloablative Stem Cell Transplantation

Group 1: Lenalidomide; Group 2: No Lenalidomide

Bendamustine DRUG

130 mg/m2/day by vein daily on day -5, -4, -3 (following Fludarabine).

Also known as: Bendamustine Hydrochloride, Bendamustine HCL, CEP-18083, SDX-105, Treanda

Group 1: Lenalidomide; Group 2: No Lenalidomide

Allopurinol DRUG

300 mg by mouth daily beginning at the start of lenalidomide therapy and continuing for 3 months.

Also known as: Lopurin, Zurinol, Zyloprim

Group 1: Lenalidomide

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years at the time of signing the informed consent form.
• Disease: CLL in relapse, after failing conventional chemo-antibody combination therapy; CLL patients who failed to achieve CR with frontline conventional chemo-antibody; CLL patients with 17p deletion; CLL in Richter's.
• Able to adhere to the study visit schedule and other protocol requirements.
• Donor: HLA compatible related (HLA-A,-B,-DRBI matched or with one-antigen mismatched) or HLA compatible unrelated.
• ECOG performance status of \</= 2 at study entry
• FEV1, FVC and DLCO \>/= 40%.
• Left ventricular EF \> 40% with no uncontrolled arrhythmias or symptomatic heart disease.
• Serum creatinine \</= 1.6 mg/dL. Serum bilirubin \< 1.6 mg/dL.
• SGPT \< 2x upper limit of normal.
• Voluntary signed, written IRB-approved informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 3 weeks prior to treatment in this study.
• Disease free of prior malignancies for \>/= 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast.
• Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to study entry.
• Disease must be chemosensitive (ie, patients must have PR or better based on CT Scans, PET Scan, and bone marrow biopsy).
• Patients suspected to have Richter's transformation (such as elevated LDH) and/or who are PET positive, should have a lymph node biopsy to assess histological status of the disease

You may not qualify if:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Use of any other experimental drug or therapy within 28 days of baseline.
• Known hypersensitivity to thalidomide, lenalidomide, bendamustine, fludarabine. For patients will unrelated donors: Known hypersensitivity to thymoglobulin.
• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
• Concurrent use of other anti-cancer agents or treatments.
• Known positive for HIV or infectious hepatitis, type A, B or C.
• Sinuses should be evaluated by either CT neck or CT sinuses to exclude infections
• Deep-vein thrombosis or pulmonary embolism within 3 months of study entry.
• History of serious infection requiring hospitalization within the last 3 months of consenting.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Celgene Corporation: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Lenalidomide; fludarabine; fludarabine phosphate; Rituximab; thymoglobulin; Antilymphocyte Serum; Stem Cell Transplantation; Bendamustine Hydrochloride; Allopurinol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Sera; Biological Products; Complex Mixtures; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Butyrates; Acids, Acyclic; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Purines

Results Point of Contact

• Title: Dr. Issa F. Khouri, MD/Professor, Stem Cell Transplantation
• Organization: The University of Texas MD Anderson Cancer Center

ikhouri@mdanderson.org

713- 745-0049

Study Officials

• Issa F. Khouri, MD, BS

  M.D. Anderson Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: May 8, 2009
• First Posted: May 12, 2009
• Study Start: May 6, 2009
• Primary Completion: October 7, 2018
• Study Completion: October 7, 2018
• Last Updated: January 27, 2020
• Results First Posted: January 27, 2020

Record last verified: 2020-01

Locations

US (1)