Total Marrow and Lymphoid Irradiation and Chemotherapy Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Lymphocytic or Myelogenous Leukemia

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Brief Title

Total Marrow and Lymphoid Irradiation and Chemotherapy Before DSCT in Treating Patients With High-Risk ALL or AML

Official Title

Phase II Study of Total Marrow and Lymphoid Irradiation (TMLI) Given in Combination With Cyclophosphamide and Etoposide as Conditioning for Allogeneic (HSCT) in Patients With High-Risk Acute Lymphocytic or Myelogenous Leukemia

Brief Summary

      This phase II trial studies the safety and efficacy of total marrow and lymphoid irradiation
      (TMLI) in combination with two chemotherapy drugs, etoposide and cyclophosphamide, as a
      preparative regimen before donor stem cell transplant in treating patients with high-risk
      acute lymphocytic leukemia (ALL) or acute myeloid leukemia (AML) who have failed previous
      therapy. Intensity-modulated radiation therapy (IMRT) uses imaging to provide a
      three-dimensional view of the area to be irradiated. Doctors can then shape and direct the
      radiation beams at the area from multiple directions while avoiding, as much as possible,
      nearby organs. TMLI is a method of using IMRT to direct radiation to the bone marrow.
      Radiation therapy is given before transplant to suppress the immune system, prevent rejection
      of the transplanted cells, and wipe out any remaining cancer cells. TMLI may allow a greater
      radiation dose to be delivered to the bone marrow as a preparative regimen before transplant
      while causing fewer side effects than standard radiation therapy.
    

Detailed Description

      PRIMARY OBJECTIVES: I. Following a patient safety lead-in, evaluate the anti-tumor activity
      of the allogeneic hematopoietic cell transplant (alloHCT) preparative regimen - TMLI,
      cyclophosphamide (Cy) and etoposide (VP-16), as assessed by 2-year progression-free survival
      (PFS).

      SECONDARY OBJECTIVES: I. Estimate overall survival (OS), cumulative incidence (CI) of
      relapse/progression, and non-relapse mortality (NRM) at 100 days, 1 year and 2 years.

      II. Evaluate early and late toxicities/complications by organ and severity, and characterize
      by organ dose/dose volume, including acute/chronic graft-versus-host-disease (GVHD),
      infection, and longer-term complications (via protocol #s 07173 and 00029).

      OUTLINE: Patients undergo image guided TMLI on days -9 to -5, receive etoposide intravenously
      (IV) on day -4 and cyclophosphamide IV on day -2, and undergo allogeneic peripheral blood
      stem cell or bone marrow transplant on day 0.

      After completion of study treatment, patients are followed up for 5 years.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Incidence of toxicity, scored on both the Bearman Scale and National Cancer Institute Common Terminology Criteria version 4.03 (Safety lead-in segment)

Secondary Outcome

 OS

Condition

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities

Intervention

etoposide

Study Arms / Comparison Groups

 Treatment (TMLI, chemotherapy)
Description:  Patients undergo image guided TMLI on days -9 to -5, receive etoposide IV on day -4 and cyclophosphamide IV on day -2, and undergo allogeneic peripheral blood stem cell or bone marrow transplant on day 0.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

87

Start Date

April 29, 2014

Completion Date

August 2023

Primary Completion Date

August 2023

Eligibility Criteria

        Inclusion Criteria:

          -  Participant has the ability and the willingness to sign the informed consent document
             (for adults only, for participants with mild cognitive abilities may use a legally
             authorized representative)

          -  Documented (signed) informed consent; the patient, family member and transplant staff
             physician (physician, nurse, and social worker) meet at least once prior to starting
             the transplant procedure; during this meeting all pertinent information with respect
             to risks and benefits to donor and recipient will be presented; alternative treatment
             modalities will be discussed; the risks are explained in detail in the enclosed
             consent forms

          -  Karnofsky performance status >= 70% =< 2

          -  Acute lymphocytic leukemia or acute myelogenous leukemia who are not in first
             remission or second remission i.e. after failing induction therapy, or in relapse or
             beyond second remission; (prior therapy with VP-16 and Cytoxan is allowed)

          -  All candidates for this study must have a human leukocyte antigen (HLA) (A, B, C, DR)
             identical siblings who is willing to donate bone marrow or primed blood stem cells or
             a 10/10 allele matched unrelated donor; a single allele mismatch at A, B, C, DR or DQ
             and a killer immunoglobulin-like receptor (KIR) mismatch at C will be allowed; all ABO
             blood group combinations of the donor/recipient are acceptable

          -  The time from the end last induction, re-induction, or consolidation regimen should be
             greater than or equal to 14 days from planned start of study treatment; Note:
             Chemotherapy given within 14 days of planned study enrollment for the purpose of
             controlling counts is permitted

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN) OR 3 x ULN for Gilbert's disease

          -  Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate
             transaminase (SGPT) =< 5 x ULN

          -  Measured creatinine clearance >= 80 ml/min per 24 hour urine collection OR serum
             creatinine =< 1.3 mg/dL

          -  Women of child bearing potential only: Negative urine or serum pregnancy test

          -  Pulmonary function tests: Forced expiratory volume in one second (FEV1) and carbon
             monoxide diffusion capacity (DLCO) (adjusted for Hb) >= 50% adjusted of predicted
             normal value

          -  Echocardiogram (ECHO) or multi gated acquisition scan (MUGA): ejection fraction of >=
             50% AND no finding of abnormal wall motion (i.e. report does not indicate that wall
             motion is "abnormal" or "altered")

          -  Electrocardiogram (EKG) showing no ischemic changes and no abnormal rhythm

          -  Agreement of men AND women-of-child-bearing-potential to use adequate contraception
             (hormonal or barrier method of birth control or abstinence) prior to study entry and
             for six months following duration of study participation; should a woman become
             pregnant or suspect that she is pregnant while participating on the trial, she should
             inform her treating physician immediately

          -  DONOR ELIGIBILITY: Donor evaluation and eligibility will be assessed as per current
             City of Hope standard operating procedure (SOP)

        Exclusion Criteria:

          -  Prior autologous or allogeneic hematopoietic stem cell

          -  Prior radiation therapy that would exclude the use of TMLI

          -  Plans during the trial to receive any other (non-trial) investigational agents, or
             concurrent biological, chemotherapy, or radiation therapy; (chemotherapy for white
             blood count control is permitted)

          -  Uncontrolled illness including ongoing or active infection

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to etoposide

          -  Patients with other active malignancies are ineligible for this study, other than
             localized malignancies

          -  Patients with psychological or medical condition that patient's physician deems
             unacceptable to proceed to allogeneic hematopoietic stem cell transplantation

          -  Women who are planning to become pregnant or breast feed during the trial

          -  Subjects, who in the opinion of the investigator, may not be able to comply with the
             safety monitoring requirements of the study
      

Gender

All

Ages

16 Years - 60 Years

Accepts Healthy Volunteers

No

Contacts

Anthony Stein, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02094794

Organization ID

14012

Secondary IDs

NCI-2014-00639

Responsible Party

Sponsor

Study Sponsor

City of Hope Medical Center

Collaborators

 National Cancer Institute (NCI)

Study Sponsor

Anthony Stein, Principal Investigator, City of Hope Medical Center


Verification Date

September 2019