DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia or Acute Leukemia in Remission

Information source: City of Hope Medical Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Previously Treated Myelodysplastic Syndromes; Secondary Acute Myeloid Leukemia

Intervention: clofarabine (Drug); melphalan (Drug); allogeneic hematopoietic stem cell transplantation (Procedure); laboratory biomarker analysis (Other); tacrolimus (Drug); sirolimus (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: City of Hope Medical Center

Official(s) and/or principal investigator(s):
Samer Khaled, Principal Investigator, Affiliation: City of Hope Medical Center

Summary

This phase II trial studies how well clofarabine and melphalan before a donor stem cell transplant works in treating patients with a decrease in or disappearance of signs and symptoms of myelodysplasia or acute leukemia. Giving chemotherapy, such as clofarabine and melphalan, before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into a patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

Clinical Details

Official title: Phase II Study of Clofarabine and High-Dose Melphalan Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation for Myelodysplasia or Acute Leukemia in Remission

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Progression-free survival

Secondary outcome:

Overall survival

Cumulative incidence of relapse/progression

Cumulative incidence of non-relapse mortality defined as death occurring in a patient from causes other than relapse or progression

Overall toxicity graded using the Bearman scale and CTCAE v4.0

Incidence and severity of acute GVHD of grades 2-4 and 3-4 according to the consensus grading

Incidence and severity of chronic GVHD scored according to National Institute of Health (NIH) consensus staging

Microbiologically documented infection

Detailed description: PRIMARY OBJECTIVES: I. Following a patient safety lead-in, determine the anti-tumor activity of clofarabine given in combination with high-dose melphalan as assessed by 2-year progression-free survival (PFS). II. Estimate overall survival (OS), cumulative incidence (CI) of relapse/progression and non-relapse mortality (NRM) at 100 days, 1 year and 2 years. III. Summarize toxicities/complications by organ and severity, including acute and chronic graft-vs-host disease (GVHD), and infection. OUTLINE: CONDITIONING REGIMEN: Patients receive clofarabine intravenously (IV) over 2 hours on days

- 9 to -5 and melphalan IV over 20 minutes on day -4.

TRANSPLANT: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.

GVHD PROPHYLAXIS: Beginning on day - 3, patients receive tacrolimus IV or orally (PO) and

sirolimus PO once daily with taper per City of Hope standard operating procedure. After completion of study treatment, patients are followed up on 30, 100, and 180 days, and then yearly for 5 years.

Eligibility

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patients in 1st or 2nd remission with acute myeloid leukemia (AML) or acute

lymphoblastic leukemia (ALL) (no circulating blasts, < 5% myeloblasts in the bone marrow, normalization of previously detected cytogenetic abnormalities, no extramedullary disease )

- High risk myelodysplastic syndrome (MDS) (not myeloproliferative neoplasms)

- Intermediate II and high risk by International Prognostic Scoring System (IPSS)

- Intermediate, high, or very high by World Health Organization (WHO)

classification-based Prognostic Scoring System (WPSS)

- Transfusion dependent

- Therapy-related MDS or MDS evolved from previous hematological disorder

(excepting myelofibrosis)

- Patients with MDS that has evolved to AML must be in remission

- Patient must not be eligible for full ablative regimens by the attending physician

- Performance status of >= 70% on the Karnofsky scale

- Women of child-bearing potential and men must agree 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 she is pregnant while participating on the trial, she should inform her treating physician immediately

- Bone marrow and peripheral blood studies must be available for confirmation of

diagnosis; cytogenetics, flow cytometry, and molecular studies (such as fms-related tyrosine kinase 3 [Flt-3] status) will be obtained as per standard practice

- Bone marrow aspirates/biopsies should be performed within 14 +/- 7 days from

registration to confirm disease remission status

- A pretreatment measured creatinine clearance (absolute value) of >= 60 mL/minute

- Patients must have a serum bilirubin =< 2. 0 mg/dl

- Patients must have serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate

pyruvate transaminase (SGPT) =< 2. 5 times the institutional upper limit of normal

- Ejection fraction measured by echocardiogram or multi gated acquisition scan (MUGA) >

50%

- Diffusing capacity of the lung for carbon monoxide (DLCO) or forced expiratory volume

in 1 second (FEV1) > 45% predicted

- Availability of an human leukocyte antigen (HLA) matched (6/6) sibling donor or 8/8

matched unrelated donor (no mismatch allowed in HLA-A, HLA-B, HLA-C and HLA-DR, donors with mismatch HLA-DQ or HLA-DPH are eligible)

- Donor stem cell source can be either peripheral blood or bone marrow

- All patients must have a psychosocial evaluation prior to transplant as per City of

Hope (COH) standard operating procedure (SOP)

- All subjects must have the ability to understand and the willingness to sign a

written informed consent

- ALL or AML patients who received chemotherapy (induction or consolidation) can

proceed to transplant once bone marrow cellularity is > 10 % with no evidence of leukemia Exclusion Criteria:

- Patients who have received a prior autologous or allogeneic transplant are excluded

- Patients with significant hepatic dysfunction (not meeting liver function tests [LFT]

eligibility criteria)

- Patients with myelofibrosis or AML evolved from myelofibrosis

- Patients with MDS evolved into AML that is not in remission

- Patients with acute promyelocytic leukemia

- Patients with myeloproliferative neoplasms

- Patients with suspected or proven central nervous system (CNS) leukemia; (diagnostic

lumbar puncture not required before enrollment)

- Uncontrolled intercurrent illness including, but not limited to ongoing or active or

poorly controlled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, poorly controlled pulmonary disease or psychiatric illness/social situations that would limit compliance with study requirements

- Pregnant or lactating women are excluded from this study

- Patients who do not agree to practice effective forms of contraception

- Human immunodeficiency virus (HIV)-positive patients are excluded from this study

- Patients are excluded if they are hepatitis B surface antigen (sAg), hepatitis B (Hep

B) core antigen (cAg), Hep B core antibody (cAb), or hepatitis C (Hep C) positive

- Patients who have received radiation therapy as part of their leukemia treatment may

be ineligible and individual cases must be presented to the study principal investigator (PI) for determination of eligibility

- Any psychiatric, social or compliance issues that, in the treating physician's

opinion, will interfere with completion of the transplant treatment and follow up

- Medical or psychiatric reasons which make the donor unlikely to tolerate or cooperate

with filgrastim (G-CSF) therapy or leukapheresis or bone marrow harvest

- Known allergies to clofarabine, melphalan, sirolimus or tacrolimus

- Patients with other active malignancies (besides AML, ALL, MDS) requiring treatment

or where there is concern of progression are ineligible for this study; however, patients with previously treated skin cancer, early stage cervical or prostate cancer may be eligible if there is no evidence of residual disease

- Cord blood as a donor source is not acceptable

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

safety monitoring requirements of the study

Locations and Contacts

City of Hope Medical Center, Duarte, California 91010, United States; Recruiting
Samer K. Khaled, MD, Phone: 800-826-4673, Email: skhaled@coh.org
Samer K. Khaled, Principal Investigator
Additional Information

Starting date: January 2014
Last updated: May 14, 2015

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017