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Autologous ROR1R-CAR-T Cells for Chronic Lymphocytic Leukemia (CLL)

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ClinicalTrials.gov Identifier: NCT02194374
Recruitment Status : Withdrawn (Study closed with no enrollment due to unavailability of reagent.)
First Posted : July 18, 2014
Last Update Posted : June 12, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief Summary:

Gene transfer is a process in which the DNA (genetic material) of certain cells is changed. In this study, gene transfer will be performed on a type of white blood cell (called T cells) to recognize leukemia cells in the same person the T cells were collected from.

The goal of this clinical research study is to learn if it is safe to give these genetically-changed T cells back to patients with CLL/SLL. Researchers also want to learn if these cells can help to attack CLL/SLL cells.


Condition or disease Intervention/treatment Phase
Leukemia Procedure: ROR1R-CAR-T Cell Infusion Drug: Fludarabine Drug: Cyclophosphamide Drug: Rituximab Drug: Bendamustine Phase 1

  Show Detailed Description

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Study to Infuse ROR1-Specific Autologous T Cells for Patients With Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)
Actual Study Start Date : January 2015
Primary Completion Date : June 2017
Study Completion Date : June 2017


Arms and Interventions

Arm Intervention/treatment
Experimental: ROR1R-CAR-T Cells

Peripheral blood mononuclear cells (PBMC) collected via venipuncture and/or steady state leukapheresis at discretion of PI. Participants receive a cycle of lympho-depleting chemotherapy as chosen by treating physician 4 to 5 days before ROR1R-CAR-T cell infusion : Fludarabine, Cyclophosphamide, and Rituximab (FCR), Bendamustine and Rituximab (BR), or Fludarabine, Bendamustine, and Rituximab (FBR).

Dose Escalation Cohort starting dose level of ROR1R-CAR-T cells/kg: 105 cell/kg infused via central venous catheter or by vein on Day 1.

Dose Expansion Cohort starting dose level of ROR1R-CAR-T cells/kg: MTD from Dose Escalation Cohort.

Procedure: ROR1R-CAR-T Cell Infusion

Dose Escalation Cohort starting dose level of ROR1R-CAR-T cells/kg: 105 cell/kg infused via central venous catheter or by vein on Day 1.

Dose Expansion Cohort starting dose level of ROR1R-CAR-T cells/kg: MTD from Dose Escalation Cohort.

Drug: Fludarabine

FCR Regimen: 25 mg/m2 by vein on Days -5, -4, and -3.

FBR Regimen: 20 mg/m2 by vein Days -5, -4, and -3.

Other Names:
  • Fludarabine Phosphate
  • Fludara
Drug: Cyclophosphamide
FCR Regimen : 250 mg/m2 by vein on Days -5, -4, and -3.
Other Names:
  • Cytoxan
  • Neosar
Drug: Rituximab

FCR and FBR Regimen: 375-500 mg/m2 by vein on Day -5.

BR Regimen: 375-500 mg/m2 by vein on Day -4.

Other Name: Rituxan
Drug: Bendamustine

BR Regimen: 70-90 mg/m2 by vein on Days -4 and -3.

FBR Regimen: 30-50 mg/m2 by vein on Days -5 to -3.

Other Names:
  • Bendamustine Hydrochloride
  • Bendamustine HCL
  • CEP-18083
  • SDX-105
  • Treanda


Outcome Measures

Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of ROR1R-CAR-T Cells for Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL) [ Time Frame: 4 weeks ]

    MTD defined as highest dose level in which 6 subjects have been treated with at most 1 subject experiencing ROR1R-CAR-T cell-related dose limiting toxicity (DLT). DLT defined as the following:

    • Common Toxicity Criteria for Adverse Effects (CTCAE) Grade ≥ 3 organ toxicity (cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary, or neurologic) not pre-existing or due to underlying malignancy and occurring within 30 days of study product infusion.
    • CTCAE Grades 3-5 allergic reactions related to study cell infusion.
    • CTCAE Grade ≥ 2 autoimmune reaction related to study product infusion.
    • Treatment-related death within 8 weeks of study product infusion.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with B cell CLL/SLL, age </= 85 years old, who have active disease that meets 2008 IWCLL/NCI-WG criteria to initiate treatment.
  2. Patients who have failed at least one line of a standard treatment, including bendamustine, fludarabine, ibrutinib, or alemtuzumab and require treatment within 2 years of completion of last treatment regimen or untreated patients with del17p by FISH (high-risk) who do not have an allogeneic stem cell transplant option.
  3. At least 21 days from last cytotoxic chemotherapy.
  4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) <2.
  5. Adequate hepatic function, defined as substance glutamate pyruvate transaminase (SGPT) <3 x upper limit of normal (ULN); serum bilirubin and alkaline phosphatase <2 x ULN, or considered not clinically significant by the study doctor or designee.
  6. Adequate renal function, defined as serum creatinine <2 x ULN.
  7. Able to provide written informed consent, and agree to practicing 2 forms of birth control during the study.
  8. Patients must have adequate cardiac function as indicated by New York Heart Association (NYHA) classification I or II AND left ventricular ejection fraction of >40% and adequate pulmonary function as indicated by room air oxygen saturation of >94%.

Exclusion Criteria:

  1. Surface ROR1 expression by <5% of CLL cells.
  2. Positive beta-HCG in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization or lactating females.
  3. Patients with known systemic allergy to bovine or murine products.
  4. Known positive serology for human immunodeficiency virus (HIV) or human anti-mouse antibody (HAMA).
  5. Active, uncontrolled autoimmune phenomenon autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura (AIHA, ITP) requiring steroid therapy.
  6. Presence of >/= Grade 3 non-hematologic toxicity common terminology criteria (CTC) version 4 from the previous treatment.
  7. Concurrent use of investigational therapeutic agent.
  8. Prior allogeneic hematopoietic stem-cell transplantation if evidence of donor chimerism persists. Patients with exclusively autologous hematopoiesis are eligible.
  9. Refusal to participate in the long-term follow-up protocol (2006-0676).
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): NCT02194374


Sponsors and Collaborators
M.D. Anderson Cancer Center
CLL Global Research Foundation Alliance
Investigators
Principal Investigator: William G. Wierda, MD, PHD, BS M.D. Anderson Cancer Center
More Information

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02194374     History of Changes
Other Study ID Numbers: 2012-0932
NCI-2014-01715 ( Registry Identifier: NCI CTRP )
First Posted: July 18, 2014    Key Record Dates
Last Update Posted: June 12, 2017
Last Verified: June 2017

Keywords provided by M.D. Anderson Cancer Center:
ROR1-specific T cells
Leukemia
Chronic lymphocytic leukemia
CLL
Small lymphocytic lymphoma
SLL
B cell
Fludarabine
Fludarabine Phosphate
Fludara
Cyclophosphamide
Cytoxan
Neosar
Rituximab
Rituxan
Bendamustine
Bendamustine Hydrochloride
Bendamustine HCL
CEP-18083
SDX-105
Treanda

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Cyclophosphamide
Fludarabine phosphate
Rituximab
Bendamustine Hydrochloride
Fludarabine
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents