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
May 12, 2014
Completion Date
August 1, 2023
Primary Completion Date
August 1, 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
May 2022