Clinical Trials /

Cyclophosphamide and Alemtuzumab In Lymphoma

NCT03132584

Description:

This research study is studying a combination of chemotherapy drugs as a possible treatment for aggressive lymphoma that has not responded to standard treatment. The names of the study interventions involved in this study are: - Cyclophosphamide - Alemtuzumab

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Mature B-Cell Lymphoma/Leukemia
  • Mature T-Cell and NK-Cell Lymphoma/Leukemia
  • Non-Hodgkin Lymphoma
  • Transformed Lymphoma
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Cyclophosphamide and Alemtuzumab In Lymphoma
  • Official Title: A Phase 1 Study of Cyclophosphamide and Alemtuzumab in CD52 Positive Relapsed/Refractory Double-Hit Lymphoma, Diffuse Large B-cell Lymphoma or High Grade B-cell Lymphoma, NOS With MYC and BCL-2 Over-expression, MYC-Positive Transformed Follicular Lymphoma, and CD52 Positive Mature T-cell Lymphoproliferative Disorder

Clinical Trial IDs

  • ORG STUDY ID: 17-034
  • NCT ID: NCT03132584

Conditions

  • Non Hodgkin Lymphoma
  • High-grade B-cell Lymphoma
  • CD52 Positive Non-Hodgkin Lymphoma
  • DLBCL or High-grade B-cell Lymphoma NOS

Interventions

DrugSynonymsArms
CyclophosphamideEndoxan, Cytoxan, Lyophilized Cytoxan, Neosar, Revimmune, Procytox, CycloblastinCyclophosphamide and Alemtuzumab
AlemtuzumabCampathCyclophosphamide and Alemtuzumab

Purpose

This research study is studying a combination of chemotherapy drugs as a possible treatment for aggressive lymphoma that has not responded to standard treatment. The names of the study interventions involved in this study are: - Cyclophosphamide - Alemtuzumab

Detailed Description

      This research study is a Phase I clinical trial, which tests the safety of an
      investigational intervention and also tries to define the appropriate dose of the
      investigational intervention to use for further studies. "Investigational" means that the
      intervention is being studied.

      The FDA (the U.S. Food and Drug Administration) has not approved alemtuzumab for aggressive
      lymphoma but it has been approved for other uses.

      In this research study, the investigators are studying the combination of cyclophosphamide
      and alemtuzumab in participants with several types of aggressive lymphoma which are positive
      for a protein called CD52, the target of alemtuzumab. Studies in laboratory models of CD52
      positive lymphoma showed the combination of cyclophosphamide and alemtuzumab was very
      effective. Cyclophosphamide causes a specific type of immune cell, called a macrophage, to
      attack lymphoma cells treated with alemtuzumab. Both drugs have been used in participants
      with lymphoma but have not been previously combined in this way. The investigators hope to
      identify the highest dose of the drugs that can be safely given together and to see if the
      combination if effective in treating these lymphomas.
    

Trial Arms

NameTypeDescriptionInterventions
Cyclophosphamide and AlemtuzumabExperimentalAfter the screening procedures confirm participation in the research study: The investigators are looking for the highest dose of the combination of study drugs that can be administered safely without severe or unmanageable side effects in participants that have CD52 positive aggressive lymphoma. Not everyone who participates in this research study will receive the same dose of the study drug. The dose given will depend on the number of participants who have been enrolled in the study prior and how well the dose was tolerated. Cyclophosphamide Alemtuzumab
  • Cyclophosphamide
  • Alemtuzumab

Eligibility Criteria

        Inclusion Criteria:

          -  Participants must have histologically confirmed non-Hodgkin lymphoma and be
             considered ineligible for standard curative therapeutic options, including high dose
             chemotherapy with autologous stem cell rescue.

          -  Participants with the following subtypes of CD52 positive non-Hodgkin lymphoma
             (defined as ≥ 50% positive staining by immunohistochemical staining or flow cytometry
             by local lab) will be considered eligible:

          -  High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements (DHL)

          -  DLBCL or high-grade B-cell lymphoma NOS or B-cell lymphoma unclassifiable with
             features intermediate between Burkitt lymphoma and diffuse large B-cell lymphoma with
             MYC and BCL2 protein over-expression by immunohistochemical (IHC) staining as defined
             by MYC expression in ≥ 40% of cells and BCL2 positivity ≥ 50% (DOL)

          -  Transformed lymphoma with MYC rearrangement by FISH or over-expression by IHC, as
             above

          -  CD52 positive mature T-cell lymphoproliferative disorder

          -  There is no limit to the prior number of chemotherapy regimens. Patients with prior
             autologous or allogeneic stem cell transplantation, as well as prior therapy with
             cyclophosphamide or alemtuzumab, are eligible.

          -  Age ≥ 18 and ≤75

          -  ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)

          -  Participants must have normal organ and marrow function as defined by peripheral
             blood values below:

               -  leukocytes ≥1,000/mcL

               -  absolute neutrophil count ≥500/mcL

               -  platelets ≥25,000/mcL

               -  total bilirubin ≤ 2 × institutional upper limit of normal (ULN) unless related
                  to Gilbert's disease

               -  AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN

               -  creatinine clearance < 1.5 x institutional ULN

          -  Ability to understand and the willingness to sign a written informed consent
             document.

        Exclusion Criteria:

          -  Participants who have had chemotherapy or radiotherapy within 1 weeks (4 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from adverse events due to agents administered more than 4 weeks earlier.

          -  Participants who are receiving any other investigational agents for their lymphoma.

          -  Participants receiving corticosteroids within the past 1 week.

          -  Participants with known active CNS involvement by lymphoma should be excluded from
             this clinical trial because of their poor prognosis and because they often develop
             progressive neurologic dysfunction that would confound the evaluation of neurologic
             and other adverse events.

          -  History of allergic reactions attributed to cyclophosphamide or alemtuzumab

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, uncontrolled hematuria related to bladder injury or psychiatric
             illness/social situations that could limit compliance with study requirements.

          -  Pregnant women are excluded from this study because cyclophosphamide and alemtuzumab
             at these doses have the potential for teratogenic or abortifacient effects. Because
             there is an unknown but potential risk for adverse events in nursing infants
             secondary to treatment of the mother with these agents, breastfeeding should be
             discontinued. Negative serum pregnancy test will be required for women of
             childbearing potential.

          -  HIV-positive participants on combination antiretroviral therapy are ineligible
             because of the increased risk of lethal infections when treated with
             marrow-suppressive therapy.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:MTD of Cyclophosphamide and Alemtuzumab
Time Frame:28 days
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall Response Rate
Time Frame:12 Months
Safety Issue:
Description:Non-Hodgkin Lymphoma Response Criteria, which will be reported descriptively
Measure:Complete Response Rate
Time Frame:12 Months
Safety Issue:
Description:Non-Hodgkin Lymphoma Response Criteria, which will be reported descriptively
Measure:Progression Free Survival
Time Frame:up to 5 years
Safety Issue:
Description:Progression-free will be estimated using the method of Kaplan and Meier.
Measure:Overall Survival
Time Frame:up to 5 years
Safety Issue:
Description:Overall survival will be estimated using the method of Kaplan and Meier.
Measure:Response Rate
Time Frame:28 Days
Safety Issue:
Description:Assess response by PET/CT and in the bone marrow after one cycle of therapy

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Non Hodgkin Lymphoma

Last Updated

April 26, 2017