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

NCT01885689 | Active Not Recruiting Phase 2 Results DMC

• 2 other identifiers: 13130NCI-2013-01193
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief 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 (disease is in remission), or chronic myelomonocytic 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. Giving clofarabine and melphalan before transplant may help prevent the cancer from coming back after transplant, and they may cause fewer side effects than standard treatment.

Conditions

Adult Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia in Remission; Myelodysplastic Syndrome; Secondary Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Therapy-Related Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival at 2 Years

  Progression-free survival (PFS) is defined as time from start of protocol treatment to disease relapse/progression, death or last contact, whichever occurs first. Progression-free survival was estimated using the Kaplan-Meier method; the 95% confidence interval was calculated using Greenwood's formula.

  From start of protocol treatment to death due to any cause, disease relapse/progression, or last follow-up, whichever comes first, assessed up to 2 years.

Secondary Outcomes (1)

• Overall Survival at 2 Years

  From start of protocol treatment to death due to any cause, or last follow-up, whichever comes first, assessed up to 2 years.

Study Arms (1)

Treatment (clofarabine, melphalan, transplant)

EXPERIMENTAL

CONDITIONING REGIMEN: Patients receive clofarabine IV over 2 hours on days -9 to -5 and melphalan IV over 30 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 PO and sirolimus PO once daily with taper per City of Hope standard operating procedure.

Drug: clofarabine; Drug: melphalan; Procedure: allogeneic hematopoietic stem cell transplantation; Drug: tacrolimus; Drug: sirolimus; Other: Pharmacological Study

Interventions

clofarabine DRUG

Given IV

Also known as: CAFdA, Clofarex, Clolar

Treatment (clofarabine, melphalan, transplant)

melphalan DRUG

Given IV

Also known as: Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin

Treatment (clofarabine, melphalan, transplant)

allogeneic hematopoietic stem cell transplantation PROCEDURE

Undergo allogeneic hematopoietic stem cell transplant

Treatment (clofarabine, melphalan, transplant)

tacrolimus DRUG

Given IV or PO

Also known as: FK 506, Prograf

Treatment (clofarabine, melphalan, transplant)

sirolimus DRUG

Given PO

Also known as: AY 22989, Rapamune, rapamycin, SLM

Treatment (clofarabine, melphalan, transplant)

Pharmacological Study OTHER

Correlative studies

Treatment (clofarabine, melphalan, transplant)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients in 1st or 2nd remission with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), who are eligible for stem cell transplant. Remission defined as no circulating blasts, \< 5% blasts in the bone marrow, normalization of previously detected cytogenetic abnormalities, no extramedullary disease
• High risk myelodysplastic syndrome (MDS)
• 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 chronic myelomonocytic leukemia (CMML) are allowed to be enrolled
• Patients with MDS that has evolved to AML must be in remission
• Patients must not be eligible for full ablative regimens by the attending physician
• Patients with AML or MDS arising from myeloproliferative neoplasm can be enrolled after principal investigator (PI) approval on case to case basis, depends on the spleen size and degree of bone marrow fibrosis
• 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 Flt-3 status) will be obtained as per standard practice
• Bone marrow aspirates/biopsies should be performed within 28 (+ 4 day window) days from registration to confirm disease remission status
• A pretreatment measured creatinine clearance (absolute value) of \>= 60 mL/minute

You may not qualify if:

• 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 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 and 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 antibody (cAb), or hepatitis C (Hep C) positive. Patients with Hepatitis B cAB positive and Hepatitis B PCR negative are eligible if they started prophylactic treatment prior to registration to trial
• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic

Interventions

Clofarabine; Melphalan; Tacrolimus; Sirolimus

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Macrolides; Lactones

Results Point of Contact

• Title: Dr. Monzi M.Al Malki, MD
• Organization: City of Hope

malmalki@coh.org

626-359-8111

Study Officials

• Monzr Al Malki

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2013
• First Posted: June 25, 2013
• Study Start: February 10, 2014
• Primary Completion: December 27, 2019
• Study Completion (Estimated): September 21, 2026
• Last Updated: November 14, 2025
• Results First Posted: April 4, 2023

Record last verified: 2025-11

Locations

US (1)